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M/s. Ishanga Life Science Pvt. Ltd.
Madhvas, Tal. Kalol, Dist.: Panchmahal
M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 1
ANNEXURE- I
PROPOSED TERMS OF REFERENCE
As per standard ToR of organic manufacturing sector issued by MoEF&CC.
M/s. Ishanga Life Science Pvt. Ltd.
Madhvas, Tal. Kalol, Dist.: Panchmahal
M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 2
ANNEXURE-II
LIST OF DIRECTORS
Sr. No. Name of Directors Residential Address Contact no.
1. Mr. Ramlal Maru 33,34-Narmada Nagar, Kanjari Road, Halol 9825033071
2. Mr. Jigar Maru 33,34-Narmada Nagar, Kanjari Road, Halol 9722221941
3. Ms. Tanvi Tank C-25/26, Uma society, Kanjari Road, Halol 9619680061
4. Ms. Avani Bhattacharya B-302, Surya Kiran Society, Charwada Road, Vapi 7715086528
M/s. Ishanga Life Science Pvt. Ltd.
Madhvas, Tal. Kalol, Dist.: Panchmahal
M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 3
ANNEXURE-III
PLAN LAY OUT
M/s. Ishanga Life Science Pvt. Ltd.
Madhvas, Tal. Kalol, Dist.: Panchmahal
M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 4
ANNEXURE- IV
LIST OF PRODUCTS WITH PRODUCTION CAPACITY
Sr.
No. Name of Products CAS No.
Capacity
(MT/Month)
End usage in mfg
following bulk drug
1 5-Nitrofurfural diacetate 92-55-7 3 Nitrofurantoin
2 1 amino hydantoin 2827-56-57 3 Nitrofurantoin
3 Phosphoryl choline chloride, calcium
salt 72556-74-2 7 Citicoline
4 Citicoline (CTS) tech 33818-15-4 5 Citicoline
5 2-(4-Aminopentyl (ethyl) amino)
ethanol 69559-11-13 10
Hydroxy chloroquin
sulphate
6 3-Quinuclidinone 3731-38-2 10 Solesenacin &
pemilin
7 1-Ethyl-3-(3-Dimethylaminopropyl)
Carbodimide Hydrochloride 25952-53-8 15
Intermediate for
Gliptin Series API
8 3-(1-Cyanoethyl) Benzoic Acid 5537-71-3 15 Ketoprofen
intermediate
9
1-(p-methoxy benzyl)-
1,2,3,4,5,6,7,8,Octahydro iso quinaline-
S-octa base
30356-07-1 8 Dextromethorphan
hydrobromide
10 Dextrometharphin free base 6700-34-1 8 Dextromethorphan
hydrobromide
11
Cis-2-(2,4-Dichloro phenyl)-2-(1H-
1,2,4-triazol-1-yl-methyl)-1,3-
dioxolan-4-yl methyl methane
sulfonate-
67914-86-7 10 Itraconazole
12
cis-2-(2,4-Dichloro phenyl)-2-(1H-
1,2,4-triazol-1-yl-methyl)-1,3-
dioxolan-4-yl methyl methane
sulfonate - CRUDE
67914-86-7
8 Itraconazole
13 Phenyl (1h pyrrole-2-yl)methanone –
tricarboxylate crude 136116-84 10 Ketorolac
14
(-)-1-[(4-Chlorophenyl)phenylmethyl]-
4-[(4-methylphenyl) sulfonyl]
piperazine
163837-56-7 6 Levocetrizine
15 p-Chloro benzhydryl piperazine 303-26-4 6 Levocetrizine
M/s. Ishanga Life Science Pvt. Ltd.
Madhvas, Tal. Kalol, Dist.: Panchmahal
M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 5
Sr.
No. Name of Products CAS No.
Capacity
(MT/Month)
End usage in mfg
following bulk drug
16 2,3 pyrridine Benzyle carboxylate
Hydrate Chloro compound 151213-40-0 5 Moxyfloxacin
17 3,4-dimethoxy-2-chloro methyl
pyridine 169905-10-6 10 Pentaprozole
18 pentaprozole sulphide 102625-64-9 10 Pentaprozole
19 Pregabalin (Racemic) 148553-50-8 8 Pregabalin
20 11-Piperazinyl-dibenzo(b,f) (1,4)-
thiazepine hydrochloride 111974-74-4 8 Quetiapine
21
11-[4-[2-(2-Hydroxy ethoxy) ethyl]-1-
piperazinyl] dibenzo (b, f) (1, 4)
thiazepine hemifumarate
111974-72-2 8 Quetiapine
22
2-[(4-(3-methoxypropoxy)-3-methyl-
2-pyridinyl)methyl]thio]-1H-
benzimidazole
117977-21-6 10 Rabeprazole
23
2-[4-(3-methoxypropoxy)-3-methyl-2-
pyridinyl]methyl]sulfinyl]-1H-
benzimidazole
117977-21-6 10 Rabeprazole
Total ---- 193 ----
M/s. Ishanga Life Science Pvt. Ltd.
Madhvas, Tal. Kalol, Dist.: Panchmahal
M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 6
ANNEXURE – V
LIST OF RAW MATERIALS WITH CONSUMPTION QUANTITY
Sr No Raw Material CAS No. Capacity (MT/Month)
1 Cyclohexane Ethylamine 3399-73-3 7.00
2 Methane sulfonyl chloride 124-63-0 3.58
3 Sodium hydroxide 1310-73-2 7.02
4 1,2,4-Triazole 288-88-0 7.00
5 2,3 pyrridne dicarboxylic acid 89-00-9 6.40
6 2,3-Dimethyl-4-nitropyridine N-oxide 37699-43-7 8.40
7 2-Aminodiphenyl sulphide 1134-94-7 4.70
8 2-Bromo butane 78-76-2 11.10
9 2-chloro ethanol 107-07-3 2.60
10 2-Chloroethoxy ethanol 628-89-7 6.79
11 2-furaldehyde diacetate 92-55-7 61.20
12 2-mercapto benzimidazole 583-39-1 11.40
13 2-Propanone 110-20-3 11.88
14 3-Methoxy Propanol 1589-49-7 5.46
15 4-[4-[4-(4-methoxy phenyl)-1-acetic acid
104-01-8 7.00
16 4-[4-[4-(4-methoxy phenyl)-1-piperazinyl]phenyl]-
3H-1,2,4-triazol-3-one 74853-07-9 11.10
17 5 difluoro methoxy 2 mercapto benzimidazole 64-19-7 10.91
18 Acetic acid (Fresh+ Recovered)
64-19-7 220.14
19 Acetonitrile (Fresh+ Recovered) 75-05-8 254.44
20 Acetic anhydride 108-24-7 86.17
21 Acetone (Fresh+ Recovered) 67-64-1 216.80
22 Activated Carbon 7440-44-0 0.58
23 Aluminium Chloride 7446-70-0 0.24
24 Ammonia formate 540-69-2 0.02
25 Ammonia solution 7664-41-7 11.20
26 Ammonium Sulphate 7783-20-2 9.44
27 Sulfuric acid 7664-93- 7.15
28 Benzoic Acid 65-85-0 34.00
29 Benzyl amine 100-46-9 8.74
30 Benzyl chloride 100-44-7 8.00
31 Bis 2 chloro ethylene hydrochloride 821-48-7 9.48
32 Bromine 7726-95-6 5.08
33 Calcium Carbonate 1317-65-3 10.78
34 Carbon 7440-44-0 36.39
35 Catalyst (DCC) 538-75-0 9.49
36 Caustic Flakes 1310-73-2 72.72
M/s. Ishanga Life Science Pvt. Ltd.
Madhvas, Tal. Kalol, Dist.: Panchmahal
M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 7
37 Chloro- 2- Pentanone 5891-21-4 18.20
38 Chloroform (Fresh+ Recovered)
67-66-3 1227.10
39 cis-[(2-bromomethyl)-2-(2,4-dichlorophynyl)-1,3-
dioxolan-4-yl methyl] benzoate 61397-56-6 20.00
40 Cyclo hexynyl ether 78917-92-7 5.25
41 Cytidine Monophospahte (CMP ) 67-63-6 7.20
42 Di ethyl Malonate 105-53-3 15.58
43 Di Methyl Carbonate 616-38-6 51.00
44 Di n Propyl amine 142-84-7 565.50
45 Dichloromethane 75-09-2 350.78
46 Diiso propyl ethyl amine 36340-89-3 11.62
47 Dimethyl formamide 68-12-2 62.13
48 Dimethyl Malenate 108-59-8 10.56
49 Dimethyl sulfoxide 67-68-5 44.40
50 Dimethyl sulphide 75-18-3 9.00
51 D-Mandalic acid 611-71-2 6.05
52 DMF 68-12-2 18.92
53 D-tartaric acid 147-71-7 4.00
54 EDC (Fresh+ Recovered) 25952-53-8 124.80
55 Ethanol 64-17-5 50.40
56 Ethyl acetate (Fresh+ Recovered) 141-78-6 212.65
57 Ethyl chloro formate 541-41-3 8.58
58 Ethyl Chloro acetate (Fresh+ Recovered) 105-39-5 286.00
59 Ethyl Cyano acetate 105-56-6 5.98
60 Ethyl Formate 109-94-4 12.75
61 Ethyl Piperidine Carboxylate 1126-09-6 14.30
62 Ethylisothiocynate 542-85-8 14.70
63 Formaldehyde 50-00-0 67.08
64 Fumaric acid 110-17-8 3.40
65 Hcl (Fresh+ Recovered) 7647-01-0 147.25
66 Hydrazine Hydrate 10217-52-4 14.10
67 Hydrobenzoic acid 99-96-7 7.47
68 Hydrobromic acid 10035-10-6 38.27
69 Hydrogen Gas 1333-74-0 46.40
70 Hydrogen peroxide 7722-84-1 7.03
71 Hyflow 61790-53-2 1.66
72 Ice 7789-20-0 23.00
73 IPA 67-63-0 11.68
74 Iso Propyl HCL 51639-49-7 0.60
75 Isovelaraldehyde 590-86-3 4.41
76 L+tartaric acid 526-83-0 15.05
77 Liquod Ammonia 1336-21-6 36.20
M/s. Ishanga Life Science Pvt. Ltd.
Madhvas, Tal. Kalol, Dist.: Panchmahal
M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 8
78 Maltol 118-71-8 9.00
79 MDC (Fresh+ Recovered) 75-09-2 655.27
80 Megnesium acetate 142-72-3 8.80
81 Megnesium oxide 1309-48-4 5.28
82 Methanol (Fresh+ Recovered) 67-56-1 2014.07
83 Methanolic Ammonia 1336-21-6 18.20
84 Methanolic Hcl 7647-01-0 7.20
85 Methyl Chloroacetate 96-34-4 2.21
86 Methylene chloride 75-09-2 49.28
87 Morpholine 110-91-8 10.96
88 N, N-Dimethylaniline 121-69-7 1.66
89 N,N Dimethyl-1,3-Propanediamine 109-55-7 294.00
90 NaoH flakes 1310-73-2 7.70
91 N-Ethyl ethanol amine 110-73-6 22.75
92 n-Heptane 142-82-5 28.20
93 N-Hexane 110-54-3 13.43
94 Nitric acid 7697-37-2 8.85
95 Nitrogen gas 7727-37-9 3.22
96 N-methyl pyrrolidinone 872-50-4 13.58
97 Orgno Copper Catalyst 7440-58-8 0.91
98 Palladium carbon 5/3/7440 1.74
99 Parachloro benzo phenon 134-85-0 10.00
100 Phenylchloroformate 1885-14-9 4.38
101 Phosphorous Oxychloride 10025-87-3 17.34
102 Phosporic acid 7664-38-2 64.80
103 Phosporous pentaoxide 1314-56-3 28.19
104 Piperazine 110-85-0 5.17
105 Pocl3 10025-87-3 42.80
106 Poly phosphoric acid 8017-16-1 22.75
107 Potassium 7440-09-7 9.90
108 Potassium carbonate 584-08-7 72.30
109 Potassium Hydroxide 1310-58-3 14.86
110 Potassium Tert- Butoxide 865-47-4 5.72
111 Propanone - 67-64-1 3.78
112 PTSC 98-59-9 7.83
113 Pyridine 110-86-1 0.89
114 Pyrrole 109-97-7 46.00
115 R-(+) ∞ Phenyl ethyl amine 3886-69-9 5.77
116 Raney Nickel 12003-78-0 7.28
117 Side Chain (Phosporyl Choline chloride) 4826-71-5 18.00
118 Soda ash 497-19-8 26.44
119 Sodium bi carbonate 144-55-8 2.44
120 Sodium carbonate 497-19-8 7.67
M/s. Ishanga Life Science Pvt. Ltd.
Madhvas, Tal. Kalol, Dist.: Panchmahal
M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 9
With representative the Product’s raw material consumption is given below:
sr.
No. Product wise Raw materials CAS No.
Quantity
MT/MT MT/Month
1 5-Nitrofurfural diacetate 92-55-7 1.000 3.00
2-furaldehyde diacetate 92-55-7 1.76 5.29
Pyridine 110-86-1 0.59 1.76
Acetic anhydride 108-24-7 5.88 17.65
Sufuric Acid 7664-93-9 2.94 8.82
Nitric acid 7697-37-2 2.94 8.82
Acetic acid 64-19-7 2.94 8.82
Sodium Hydroxide 1310-73-2 0.59 1.76
Total 17.647 52.941
2 1 amino hydantoin 2827-56-57 1.000 3.00
Hydrazine Hydrate 10217-52-4 1.250 3.750
Urea 57-13-6 1.125 3.375
Acetone 67-64-1 15.000 45.000
2-Propanone semicarbazone 110-20-3 0.813 2.438
Sodium Methoxide 124-41-4 0.375 1.125
Methyl Chloroacetate 96-34-4 0.438 1.313
Propanone semiaminohydrantoin 2827-56-7 0.750 2.250
Hcl 7647-01-0 0.188 0.563
121 Sodium Cyanide 143-33-9 20.40
122 Sodium Hydroxide 1310-73-2 48.72
123 Sodium Hypochlorite 7681-52-9 82.60
124 Sodium Iodide 7681-82-5 0.58
125 Sodium Methoxide 124-41-4 25.29
126 Sodium mono chloro acetate 3926-62-3 3.96
127 Sodium Sulfate 7757-82-6 16.03
128 Sodium tungaste 13472-45-2 0.22
129 Sodiumhydroxide 1310-73-2 7.03
130 Sulfuric Acid (Fresh+ Recovered) 7664-93-9 336.45
131 TBAB 1643-19-2 1.50
132 Tetrabutylammonium bromide 311-28-4 1.18
133 THF 109-99-9 21.00
134 Thionyl chloride 9/7/7719 13.87
135 Toluene (Fresh+ Recovered) 108-88-3 1779.66
136 Triethyl amine 121-44-8 5.48
137 Urea 57-13-6 10.70
138 Xylene (Fresh+ Recovered) 1330-20-7 364.00
M/s. Ishanga Life Science Pvt. Ltd.
Madhvas, Tal. Kalol, Dist.: Panchmahal
M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 10
Total 19.938 59.813
3 Phosphoryl choline chloride, calcium
salt 72556-74-2 1.000 7.00
Choline Chloride 67-48-1 1.111 7.778
Phosporyl chloride 4826-71-5 1.444 10.111
Calcium Chloride 10043-52-4 0.556 3.889
Calcium Carbonate 1317-65-3 1.111 7.778
Methanol 67-56-1 3.333 23.333
Total 7.556 52.889
4 Citicoline (CTS) tech 33818-15-4 1.000 5.00
Cytidine Monophospahte (CMP ) 67-63-6 1.429 7.143
Methanol 67-56-1 32.143 160.714
Morpholine 110-91-8 1.143 5.714
DCC (N,N'-Dicyclohexylcarbodiimide) 538-75-0 1.857 9.286
Phosphorul Choline chloride 4826-71-5 3.571 17.857
Methanolic Hcl 7647-01-0 1.429 7.143
IPA 67-63-0 14.286 71.429
Activated Carbon 7440-44-0 0.114 0.571
Sodium Hydroxide 1310-73-2 0.143 0.714
Ethanol 64-17-5 10.000 50.000
Total 66.114 330.571
5 2-(4-aminopentyl (ethyl) amino)
ethanol 69559-11-13 1.000 20.00
5 Chloro 2 pentanone 5891-21-4 0.909 18.182
Xylene (Fresh) 1330-20-7 0.909 18.182
N-Ethyl ethanol amine 110-73-6 1.136 22.727
Orgno Copper Catalyst 7440-58-8 0.045 0.909
Raney Nickel 12003-78-0 0.364 7.273
Methanol 67-56-1 13.636 272.727
Methanolic Ammonia 1336-21-6 0.909 18.182
Hydrogen Gas 1333-74-0 1.818 36.364
Total 19.727 394.545
6 3-Quinuclidinone 3731-38-2 1.000 10.00
Ethyl Piperidine Carboxylate 1126-09-6 1.429 14.29
Toluene (Fresh) 108-88-3 2.857 28.57
Ethyl Chloro acetate 105-39-5 3.071 30.71
Potassium Tert- Butoxide 865-47-4 1.571 15.71
Hcl Acid solution 7647-01-0 1.429 14.29
M/s. Ishanga Life Science Pvt. Ltd.
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M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 11
Sulfuric Acid 7664-93-9 0.714 7.14
Sodium hydroxide 1310-73-2 1.786 17.86
Chloroform (Fresh) 67-66-3 11.429 114.29
IPA Hcl 70849-64-8 0.714 7.14
Total 25.00 250.00
7 1-ethyl-3-(3-dimethylaminopropyl)
carbodimide. hydrochloride 25952-53-8 1.000 20.00
Ethylisothiocynate 542-85-8 0.732 14.63
Chloroform 67-66-3 14.459 289.17
N,N Dimethyl-1,3-Propanediamine 109-55-7 0.927 18.54
Calcium Carbonate 1317-65-3 0.537 10.73
Potassium Hydroxide 1310-58-3 0.463 9.27
Acetonitrile 75-05-8 12.195 243.90
Hcl (Gas) 7647-01-0 0.244 4.88
Total 29.56 591.12
8 3-(1-cyanoethyl) benzoic acid 5537-71-3 1.000 30.00
Benzoic Acid 65-85-0 1.111 33.33
Formaldehyde 50-00-0 2.000 60.00
Methanol (Fresh) 67-56-1 0.222 6.67
Dichloromethane 75-09-2 21.111 633.33
Aluminium Chloride 7446-70-0 0.778 23.33
Sulfuric Acid 7664-93-9 10.000 300.00
Sodium Cyanide 143-33-9 0.667 20.00
Di Methyl Carbonate 616-38-6 1.667 50.00
Total 37.56 1126.67
Product wise raw materials for remaining products will be covered in EIA report.
M/s. Ishanga Life Science Pvt. Ltd.
Madhvas, Tal. Kalol, Dist.: Panchmahal
M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 12
ANNEXURE- VI
MANUFACTURING PROCESS:
1) 5-Nitrofurfural diacetate
Process:
Acetic anhydride and Sulphuric acid is treated with Nitric acid gives 5-NLTA which on
Hydrolysis gives 5-Nitrofurfural diacetate.
Chemical Reaction:
Material Balance & Flow Diagram:
2) 1-Amino hydantoin
Process:
Hydrazine Hydrate is treated with Urea in presence of Methanol gives 2-PSB which on
cyclization with Methyl Chloroacetate gives PSAH.
PSAH further treated with HCl to give final product 1-Amino hydantoin.
M/s. Ishanga Life Science Pvt. Ltd.
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M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 13
Chemical Reaction:
Material Balance & Flow Diagram:
3) Phosphoryl Choline chloride, Calcium salt.
Process:
Choline chloride is reacted with Phosphorous oxychloride to give Phosphroryl choline chloride,
which subjected to hydrolysis and converted to Calcium salt to give the desired product
Phosphoryl Choline chloride , Calcium salt.
Chemical Reaction:
M/s. Ishanga Life Science Pvt. Ltd.
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M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 14
Material Balance & Flow Diagram:
4) Citicoline intermediate – 1 (CTS Tech)
Process:
Cytidine Monophospahte (CMP) dissolved in Methanol in presence of Dicyclohexy Carbodamide
(DCC) and then condensed with Phosporyl Choline chloride at ambient temperature. After
completion of reaction the reaction mass is filtered and final product is purified in Methanol.
Chemical reaction:
Cytidine 5'-monophosphate Morpholine
(5'-CMP-morpholidate)
(5'-CMP)
OP
ON N
OH O H
OH
O
O H
O
NH 2
NHO + DCC
Methanol
OP
ON N
OH O H
N
O
O H
O
NH 2
O
(CPCC)
N+
O
P
CH 3
C H 3
C H 3 Ca
O
O
O
Cl-
Methanol
HCl
OP
ON N
OH O H
O
O
O H
O
NH 2
PN+
OCH 3
CH 3
CH 3 O-
O
IPA
DIPA + Oxalic acid
Water
Activated Carbon
Sodium hydroxide
Formic acid
Methanol + IPA
OP
ON N
OH O H
O
O
ONa
O
NH 2
PN+
OCH 3
C H 3
C H 3 O-
O
Citicoline Sodium Crude / Citicoline sodium Tech
Purification
Water
Formic acid
Sodium hydroxide
Methanol + IPA
OP
ON N
OH O H
O
O
ONa
O
NH 2
PN+
OCH 3
C H 3
C H 3 O-
O
Citicoline Acid Crude
Citicoline Sodium - API
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M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 15
Material balance & flow diagram:
5) 3-(1-CYANOETHYL) BENZOIC ACID
Process:
Benzoic acid is treated with formaldehyde in presence of aluminium chloride in dichloromethane
followed by esterification reaction with methanol in sulphuric acid gives methyl 3-(chloromethyl)
benzoate which on further treated with sodium cyanide in methanol gives methyl 3-
(cyanomethyl)benzoate.
Methyl 3-(cyanomethyl) benzoate further methylated with dimethyl carbonate in water gives 3-(1-
cyanoethyl) benzoic acid.
Chemical reaction:
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M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 16
Material balance & flow diagram:
6) 1-Ethyl-3-(3-Dimethylaminopropyl) Carbodimide Hydrochloride (EDC. HCl)
Process:
Ethyl isothiocynate treated with N,N-Dimethyl-1,3-propanediamine in presence of sodium
hypochlorite, potassium hydroxide in calcium carbonate treatment in chloroform as solvent, after
completion of reaction, reaction mass is quenched with water and isolated product 1-ethyl-3-(3-
dimethylaminopropyl) carbodimide.
Further,1-ethyl-3-(3-dimethylaminopropyl) carbodimide further treated with anhydrous
hydrochloric acid in acetonitrile solvent to give 1-ethyl-3-(3-dimethylaminopropyl) carbodimide
hydrochloride.
Chemical Reaction:
CH3 N S + NH2 N
CH3
CH3
CH3 N N N
CH3
CH3
N-[3-(dimethylamino)propyl]-N'-ethylcarbodiimide
N,N-dimethylpropane-1,3-diamineIsothiocyanatoethane
CH3 N N N
CH3
CH3
HCl
N-[3-(dimethylamino)propyl]-N'-ethylcarbodiimide.hydrochloride (EDC.HCl)
Molecular Formula = C8H17N3
Formula Weight = 155.24068
Molecular Formula = C8H17N3
Formula Weight = 155.24068
Molecular Formula = C5H14N2
Formula Weight = 102.17806
Molecular Formula = C3H5NS
Formula Weight = 87.1435
NaOCl, Chloroform
HCl
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M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 17
Material balance & flow diagram:
7) Quinuclidinone
Process:
Ethyl Piperidine 4-carboxylate has been treated with ethylchloro acetate in toluene solvent in
presence of potassium carbonate as base. Reaction mass was refluxed for completion of reaction.
Reaction mass was quenched with water. Organic layer was washed with water and toluene layer
was subjected to next reaction Insitu.
To above toluene layer charged potassium tert-butoxide and refluxed till completion of reactions.
After this charge hydrochloric acid in to reaction mass and product was extracted in water. This
acidic aqueous layer was refluxed for 24 hrs and finally product extracted in chloroform at basic
pH. Distilled chloroform and IPA.HCl was added in to it. Filter precipitated product and dried
under vacuum.
Chemical Reaction:
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Material balance & flow diagram:
8. 2-(4-AMINOPENTYL (ETHYL) AMINO) ETHANOL
Process:
5-Chloro-2-pentanone is treated with N-ethyl ethanol amine and organo-copper catalyst in xylene.
Reaction mass was refluxed till completion of reaction followed by distillation of xylene. Obtained
intermediate residue was treated with methanolic ammonia and raney nickel in methanol. After
separation of catalyst, distilled methanol to get 2-(4-aminopentyl (ethyl) amino) ethanol.
Chemical Reaction:
CH 3
Cl
O
+ CH 3 N HO H
CH 3
N
O HCH 3
O
C H 3
N
O HCH3
NH2
X ylene
C u
Raney Nickel
Methanol + NH 3
Molecular Formula = C5H
9ClO
Formula Weight = 120.57
5-chloropentan-2-one 2-(ethylam ino)ethanol
Molecular Formula= C4H
11NO
Formula Weight = 89.13 5-[ethyl(2-hydroxyethyl)am ino]pentan-2-one
Molecular Formula = C9H
19NO
2
Formula Weight = 173.25
2-[(4-am inopentyl)(ethyl)am ino]ethanol
Molecular Formula = C9H
22N
2O
Formula Weight = 174.28
M/s. Ishanga Life Science Pvt. Ltd.
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Material balance & flow diagram:
9. 1-(p-methoxy benzyl)-1,2,3,4,5,6,7,8,Octahydro iso quinaline- S-octa base
Stage-I: 1-(p-methoxy benzyl)-1,2,3,4,5,6,7,8,Octahydro iso quinaline
Process: Cyclohexenylethylamine reacts with P-methoxyphenylacetic acid in Toluene gives N-(2-
(Cyclohexen-1-yl)ethyl) -p-methoxyphenylacetamide.
Chemical Reaction:
Stage-II: 1-(p-methoxy benzyl)-1,2,3,4,5,6,7,8,Octahydro iso quinaline Mandelate
Process: N-(2-(Cyclohexen-1-yl)ethyl)-p-methoxyphenylacetamide reacts with
Phosphorusoxychloride in Toluene gives 1-(P-methoxybenzyl)-3,4,5,6,7,8, hexahydroisoquinoline.
Chemical Reaction:
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Stage-III: 1-(p-methoxy benzyl)-1,2,3,4,5,6,7,8,Octahydro iso quinaline- S-octa base
Process: 1-(P-methoxybenzyl)3,4,5,6,7,8, hexahydroisoquinoline reacts with Sodiumborohydride in
Water gives 1-(P- methoxybenzyl)1,2,3,4,5,6,7,8, octahydroisoquinoline.,8, octahydro.
Chemical Reaction:
Material Balance:
10. Dextrometharphin free base –Crude
Stage-I: (p-methoxybenzyl)-2-formyl-1,2,3,4,5,6,7,8, Octahydro iso quinaline
Process: D-1-(P-methoxybenzyl)1,2,3,4,5,6,7,8, octahydroisoquinolineMandalate reacts with Caustic
lye in water gives D-1-(P-methoxybenzyl)1,2,3,4,5,6,7 isoquinoline (S-Octabase).
Chemical Reaction:
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Stage-II: 3--methoxy-N-formylmorphian
Process: Formulation of S-Octabase with Methyl formate in presence of Sodium methoxide and
Toluene followed by neutralization with formic acid give Stage-II compound.
Chemical Reaction:
Stage-III: 3- methoxymorphian-Deformylation
Process:
Cyclization of stage-II compound in presence of Phosphoric acid give Stage-III.
Chemical Reaction:
Stage-IV
Process:
High vacuum distillation of Stage-IV give pure compound i.e. Stage-V.
Chemical Reaction:
Stage-V : Dextrometharphin free base -Crude
Process: N-methylation of Stage-IV with formaldehyde and formic acid in presence of Toluene
followed by crystallization in Acetone gives Stage-V i.e. Dextromethorphan base.
Chemical Reaction:
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Material Balance:
11. Cis-2-(2,4-Dichloro phenyl)-2-(1H-1,2,4-triazol-1-yl-methyl)-1,3- dioxolan-4-yl methyl
methane sulfonate (CRUDE)
Stage- I
Process:
2,4-Dihydro-4-[4-[4-(4-methoxyphenyl)-1-piperazinyl]phenyl]-3H-1,2,4-triazol-3-one is reacted with
2-bromo butane to give 2,4-Dihydro-4-[4-[4-(4-methoxyphenyl)-1-piperazinyl]phenyl]-2-(1-
methylpropyl)-3H-1,2,4-triazol-3-one.
N N
N
N
N
O
N N
N
N
N
O
H3CO H
3CO
H
Stage – II: 2,4-Dihydro-4-[4-[4-(4-methoxyphenyl)-1-piperazinyl]phenyl]-2-(1-methylpropyl)-3H-
1,2,4-triazol-3-one is reacted with hydro bromic acid to give 2,4-Dihydro-4-[4-[4-(4-
hydroxyphenyl)-1-piperazinyl]phenyl]-2-(1-methylpropyl)-3H-1,2,4-triazol-3-one.
N N
N
N
N
O
OH N N
N
N
N
O
H3CO
Stage – III: cis-(2-Bromo methyl)-2-(2,4-dichloro phenyl)-1,3-dioxolan-4-yl methyl benzoate is
reacted with 1H-1,2,4-triazole and the resultant is hydrolised with sodium hydroxide to give cis-2-
(2,4-dichloro phenyl)-2-(1H-1,2,4-triazol-1-yl-methyl)-1,3-dioxolan-4-yl methanol.
Cl
Cl
O
OCH
2COOC
6H
5
H
Br
Cl
Cl
O
O
NN
N
CH2OH
H
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Stage–IV: cis-2-(2,4-Dichloro phenyl)-2-(1H-1,2,4-triazol-1-yl-methyl)-1,3-dioxolan-4-yl methanol is
reacted with methane sulfonyl chloride to give cis-2-(2,4-Dichloro phenyl)-2-(1H-1,2,4-triazol-1-yl-
methyl)-1,3-dioxolan-4-yl methyl methane sulfonate (Crude).
Cl
Cl
O
O
NN
N
CH2OSO
2CH
3
H
Cl
Cl
O
O
NN
N
CH2OH
H Material Balance:
12. Cis-2-(2,4-Dichloro phenyl)-2-(1H-1,2,4-triazol-1-yl-methyl)-1,3- dioxolan-4-yl methyl
methane sulfonate (PURE)
Stage- I: 2,4-Dihydro-4-[4-[4-(4-methoxyphenyl)-1-piperazinyl]phenyl]-3H-1,2,4-triazol-3-one is
reacted with 2-bromo butane to give 2,4-Dihydro-4-[4-[4-(4-methoxyphenyl)-1-piperazinyl]phenyl]-2-
(1-methylpropyl)-3H-1,2,4-triazol-3-one.
N N
N
N
N
O
N N
N
N
N
O
H3CO H
3CO
H
Stage – II: 2,4-Dihydro-4-[4-[4-(4-methoxyphenyl)-1-piperazinyl]phenyl]-2-(1-methylpropyl)-3H-
1,2,4-triazol-3-one is reacted with hydro bromic acid to give 2,4-Dihydro-4-[4-[4-(4-
hydroxyphenyl)-1-piperazinyl]phenyl]-2-(1-methylpropyl)-3H-1,2,4-triazol-3-one.
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N N
N
N
N
O
OH N N
N
N
N
O
H3CO
Stage – III: cis-(2-Bromo methyl)-2-(2,4-dichloro phenyl)-1,3-dioxolan-4-yl methyl benzoate is
reacted with 1H-1,2,4-triazole and the resultant is hydrolised with sodium hydroxide to give cis-2-
(2,4-dichloro phenyl)-2-(1H-1,2,4-triazol-1-yl-methyl)-1,3-dioxolan-4-yl methanol.
Cl
Cl
O
OCH
2COOC
6H
5
H
Br
Cl
Cl
O
O
NN
N
CH2OH
H Stage–IV: cis-2-(2,4-Dichloro phenyl)-2-(1H-1,2,4-triazol-1-yl-methyl)-1,3-dioxolan-4-yl methanol is
reacted with methane sulfonyl chloride to give cis-2-(2,4-Dichloro phenyl)-2-(1H-1,2,4-triazol-1-yl-
methyl)-1,3-dioxolan-4-yl methyl methane sulfonate.
Cl
Cl
O
O
NN
N
CH2OSO
2CH
3
H
Cl
Cl
O
O
NN
N
CH2OH
H
Stage – V: 4-[4-[4-(4-Hydroxyphenyl)-1-piperazinyl]phenyl]-2,4-dihydro- 2-(1-
methylpropyl)-3H-1,2,4-triazole-3-one is reacted with cis-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-
1-yl-methyl)-1,3-dioxolan-4-yl methyl methane sulfonate and sodium hydroxide, in toluene and
methanol to give Itraconazole (Pure).
CH3
CH3OH N N
NO
NN
Cl
Cl
O
O
NN
N
CH2OSO
2CH
3
H
+
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Material Balance:
13. KeterolacTrimethamine INTERMEDIATES
Stage – I: Marpholine phenyl methanone
Process:
Morpholine reacted with Benzoyl chloride In presence of Toluene gives Marpholine phenyl
methanone
Chemical Reaction:
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Material Balance:
Stage-II : Phenyl (1h pyrrole-2-yl)methanone.
Process: Marpholine phenyl methanone reacted with pocl3 and pyrrole after that quenching in Ice
water isolated product gives Phenyl (1h pyrrole-2-yl)methanone.
Chemical Reaction:
Material Balance:
Stage- III
Process:
Magnesium oxide and dimethyl Malenate reacted with Ethyl Choloroformate and Sulfuric acid in
presence of Toluene gives Triethyl methane tricarboxylate.
Material Balance:
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Stage- IV: Phenyl (1h pyrrole-2-yl)methanone – tricarboxylate.
Process: Triethyl methane tricarboxylate and Phenyl (1h pyrrole-2-yl)methanone in presense of
magnesium acetate and acetic anhydride in presence of ethyl acetate gives Phenyl (1h pyrrole-2-
yl)methanone – tricarboxylate.
Chemical Reaction:
Material Balance:
Stage- V: Phenyl (1h pyrrole-2-yl)methanone – tricarboxylate.
Process: Phenyl (1h pyrrole-2-yl) methanone – tricarboxylate reacted with potassium carbonate in
presence of ethyl acetate by using TBAB catalyst Gives Phenyl (1h pyrrole-2-yl)methanone –
tricarboxylate crude.
Chemical Reaction:
Material Balance:
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Stage–VI:
Process: Phenyl (1h pyrrole-2-yl)methanone – tricarboxylate -Ketrolactrimethamin -crude .
Phenyl (1h pyrrole-2-yl)methanone – tricarboxylate reacted with Triethl amine in presence of Acetone
Gives Phenyl (1h pyrrole-2-yl)methanone – tricarboxylate -Ketrolactrimethamin -crude .
Chemical Reaction:
Material Balance:
14. (-)-1-[(4-Chlorophenyl)phenylmethyl]-4-[(4-methylphenyl) sulfonyl] piperazine
Stage-1: Reaction of p-Chloro benzo phenone (PCBP) with Ammonium formate in toluene followed
by workup gives racemic (±)-(4-Chlorophenyl) phenylmethyl amine (Stage-I Intermediate).
Chemical Reaction:
Stage-II: Treatment of Stage-I intermediate with L(+)-Tartaric acid in methanol provides the required
isomer as its tartaric acid salt, which on hydrolysis with aq. sodium hydroxide gives Levorotatory (-)-
(4-Chlorophenyl) phenylmethyl amine (Stage-II intermediate) as an oily liquid.
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Chemical Reaction:
Stage-III: Treatment of N,N-Bis (2-chloroethyl)amine hydrochloride with p-Toluene Sulphonyl
chloride in Methylene dichloride and followed by workup yields N,N-bis(2-Chloroethyl)-4-methyl
benzene sulfonamide (Stage-III intermediate)
Chemical Reaction:
Stage-IV:Condensation of Levorotatory (-)-(4-Chlorophenyl) phenyl methyl amine (Stage-II
intermediate) with N,N-bis(2-Chloroethyl)-4-methyl benzene sulfonamide (Stage-III intermediate) in
presence of Disopropyl ethylamine (DIEPA) and followed by further workup yields (-)-1-[(4-
Chlorophenyl)phenylmethyl]-4-[(4-methylphenyl)sulfonyl] piperazine (Stage-IV intermediate).
Chemical Reaction:
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Material Balance:
15. (-) P-Chloro benzhydryl piperazine
Stage-1 : Reaction of p-Chloro benzo phenone (PCBP) with Ammonium formate in toluene followed
by workup gives racemic (±)-(4-Chlorophenyl) phenylmethyl amine (Stage-I Intermediate).
Chemical Reaction:
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Stage-II: Treatment of Stage-I intermediate with L(+)-Tartaric acid in methanol provides the required
isomer as its tartaric acid salt, which on hydrolysis with aq. sodium hydroxide gives Levorotatory (-)-
(4-Chlorophenyl) phenylmethyl amine (Stage-II intermediate) as an oily liquid.
Chemical Reaction:
Stage-III: Treatment of N,N-Bis (2-chloroethyl) amine hydrochloride with p-Toluene Sulphonyl
chloride in Methylene dichloride and followed by workup yields N,N-bis(2-Chloroethyl)-4-methyl
benzene sulfonamide (Stage-III intermediate).
Chemical Reaction:
Stage-IV: Condensation of Levorotatory (-)-(4-Chlorophenyl) phenyl methyl amine (Stage-II
intermediate) with N,N-bis(2-Chloroethyl)-4-methyl benzene sulfonamide (Stage-III intermediate) in
presence of Disopropyl ethylamine (DIEPA) and followed by further workup yields (-)-1-[(4-
Chlorophenyl)phenylmethyl]-4-[(4-methylphenyl)sulfonyl] piperazine (Stage-IV intermediate).
Chemical Reaction:
Stage-V: Treatment of Stage-IV intermediate with HBr in acetic acid in presence of p Hydroxy
benzoic acid (catalyst) followed by workup gives (-) p-Chloro benzhydryl piperazine (Stage-V).
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Chemical Reaction:
Material Balance:
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16. 2,3 pyrridine Benzyle carboxylate Hydrate Chloro compound
Process:
Stage-I: 2,3 pyrridineBenzyle carboxylate
2,3 pyrridine dicarboxylic acid reacted acetic anhydride and benzyl amine In presence of Methanol
and toluene gives 2,3 pyrridineBenzyle carboxylate.
Stage-II: 2,3 pyrridineBenzyle carboxylate hydrate
2,3 pyrridine Benzyl carbaxylate reacted with Palladium carbon catalyst in presence of ethyacetate
gives 2,3 pyrridineBenzyle carboxylate hydrate.
Stage-III : 2,3 pyrridineBenzyle carboxylate Hydrate Tartrate salt
2,3 pyrridineBenzyle carboxylate hydrate reacted with tartaric acid inpresence of Water gives 2,3
pyrridineBenzyle carboxylate tartrate salt.
Stage- IV: 2,3 pyrridineBenzyle carboxylate Hydrate Chloro compound
2,3 pyrridineBenzyle carboxylate tartrate salt reacted with Alluminium chloride inpresence of Water
and toluene gives 2,3 pyrridineBenzyle carboxylate chlorcompound.
Stage-V: 2,3 pyrridineBenzyle carboxylate Hydrate Chloro compound
2,3 pyrridineBenzyle carboxylate clorocompound reacted with Hydrogenation reduction inpresence
of Water and Methanol gives Nonane compound.
Chemical Reaction:
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Material Balance:
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17. 3,4-dimethoxy-2-chloro methyl pyridine
Stage-I: Maltol is reacts with Dimethyl sulphate in presence of acetone to get 3-methoxy 2-methyl-4-
pyron.
Stage-II: 3-methoxy n-methyl-4-pyron reacts with liquor ammonia solution and ammonia acetate is
used as a catalyst crystallized by the acetone 3-methoxy 2-methyl-4-pyridone.
Stage-III: 3-methoxy 2-methyl-4-pyridone reacts with phosphorous oxychloride in presence of MDC
to get 4-chloro 3-methoxy 2-methyl-4-pyridone.
Stage-IV: 4-chloro 3-methoxy 2-methyl-4-pyridone reacts with hydrogen peroxide in presence of
acetic acid sodium tungastate is under as a catalyst 4-chloro 3-methoxy 2-methyl-4-pyridone-n-oxide.
Stage-V: 4-chloro 3-methoxy 2-methyl-4-pyridone-n-oxide reacts with methanol in presence of
sodium hydroxide to get 3,4-diethoxy-2-methyl-4-pyridone-n-oxide.
Stage-VI: 3,4-diethoxy-2-methyl-4-pyridone-n-oxide reacts with acetic anhydride and further reacts
with sodium hydroxide in presne of water to get 3,4-dimethoxy-2-hydroxy methyl pyridine.
Stage-VII: 3,4-dimethoxy-2-hydroxy methyl pyridine reacts with thionyl chloride in presence of
MDC 3,4-dimethoxy-2-chloro methyl pyridine- pantoprazole chloro.
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Chemical Reaction:
Material Balance:
18. Pentaprozole sulphide
Stage-I: Maltol is reacts with Dimethyl sulphate in presence of acetone to get 3-methoxy 2-methyl-4-
pyron.
Stage-II: 3-methoxy n-methyl-4-pyron reacts with liquor ammonia solution and ammonia acetate is
used as a catalyst crystallized by the acetone 3-methoxy 2-methyl-4-pyridone.
Stage-III: 3-methoxy 2-methyl-4-pyridone reacts with phosphorous oxychloride in presence of MDC
to get 4-chloro 3-methoxy 2-methyl-4-pyridone.
Stage-IV: 4-chloro 3-methoxy 2-methyl-4-pyridone reacts with hydrogen peroxide in presence of
acetic acid sodium tunga state is under as a catalyst 4-chloro 3-methoxy 2-methyl-4-pyridone-n-oxide.
Stage-V: 4-chloro 3-methoxy 2-methyl-4-pyridone-n-oxide reacts with methanol in presence of
sodium hydroxide to get 3,4-diethoxy-2-methyl-4-pyridone-n-oxide.
Stage-VI: 3,4-diethoxy-2-methyl-4-pyridone-n-oxide reacts with acetic anhydride and further reacts
with sodium hydroxide in presne of water to get 3,4-dimethoxy-2-hydroxy methyl pyridine.
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Stage-VII: 3,4-dimethoxy-2-hydroxy methyl pyridine reacts with thionyl chloride in presence of
MDC 3,4-dimethoxy-2-chloro methyl pyridine- pantoprazole chloro.
Stage-VIII: 5-(Difluoro methoxy)-2-mercapto benzimidazole and 2-chloromethyl-3,4-dimethoxy-
pyridine hydrochloride are condensed in the presence of sodium hydroxide and in methanol to give
5-(Difluoro methoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)-2-methyl] thiol]-1H-benzimidazole to get
pentaprozole sulphide.
Chemical Reaction:
Material Balance:
19. Pregabalin (Racemic)
Stage-I: Isovelaraldehyde is reacts with Ethyl cyan Acetate in presence of Toluene to get 2-Carboxy-
5-methyl hex-2- exotic acid ethyl ester.
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Stage-II: 2-Carboxy-5-methyl hex-2-exotic acid ethyl ester reacts with R-Phenyl |Ethyl amine in
presence of Chloroform to get 2-Carboxyethyl-3-cyano-5-methyl hexanoic acid ethyl ester.
Stage-III: 2-Carboxyethyl-3-cyano-5-methyl hexanoic acid ethyl ester reacts with Bromine in
presence of MDC to get Pregabalin (Racemic).
Chemical Reaction:
Stage-I : Preparation of 2-Carboxy-5-methyl hex-2-exotic acid ethyl ester
Stage-II : Preparation of 2-Carboxyethyl-3-cyano-5-methyl hexanoic acid ethyl ester
Stage-III : Preparation of Pregabalin (Racemic)
Stage-IV : Preparation of Pregabalin
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Material Balance:
20. 11-Piperazinyl-dibenzo(b,f) (1,4)-thiazepine hydrochloride
Process:
Stage – I: 2-Amino diphenyl sulphide is reacted with Phenylchloroformate in presence of Toluene
gives Phenyl-2-(phenyl thio) phenyl carbamate (QUE-1).
Stage – II: Phenyl-2-(phenyl thio) phenyl carbamate (QUE-1) is reactes with Poly phosphouric acid
in presence of Acetone to give Dibenzo (b, f) (1,4) thiazepine-11 (10H)-one (QUE-1I).
Stage – III: Dibenzo (b, f) (1,4) thiazepine-11 (10H)-one (QUE-1I)is reacted with Pocl3 in presence
of Piperazine to give 11-Piperazinyl-dibenzo(b,f) (1,4)-thiazepine hydrochloride.
Chemical Reaction:
Preparation of Phenyl -2- (-phenylthio)phrnyl carbamate (QUE-1)
NH2
S
NHCOOPh
S
2-Aminodiphenyl sulphide
+ C6H5-O-C-Cl
O
Na2CO3
Phenyl-2-(phenylthio)phenyl carbamate
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Preparation of Dibenzo (b, f) (1,4) thiazepine-11 (10H)-one (QUE-1I)
S
NO
Polyphosphoric acid
Dibenzo [b,f][1,4]thiazepine-11(10-H)one
HNHCOOPh
S
Phenyl-2-(phenylthio)phenyl carbamate
Preparation of 11-Piperazinyl-dibenzo(b,f) (1,4)-thiazepine hydrochloride (QUE-III HCl):
Material Balance:
Stage-I: Preparation of Phenyl-2-(phenyl thio) phenyl carbamate (QUE-1):
Stage-II: Preparation of Dibenzo (b, f) (1,4) thiazepine-11 (10H)-one (QUE-1I)
Stage-III: Preparation of 11-Piperazinyl-dibenzo(b,f) (1,4)-thiazepine hydrochloride (QUE-III)
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21. 11-[4-[2-(2-Hydroxy ethoxy) ethyl]-1-piperazinyl] dibenzo (b, f) (1, 4) thiazepine
hemifumarate
Process:
Stage – I: 2-Amino diphenyl sulphide is reacted with Phenylchloroformate in presence of Toluene
gives Phenyl-2-(phenyl thio) phenyl carbamate (QUE-1).
Stage – II: Phenyl-2-(phenyl thio) phenyl carbamate (QUE-1) is reactes with Poly phosphouric acid
in presence of Acetone to give Dibenzo (b, f) (1,4) thiazepine-11 (10H)-one (QUE-1I).
Stage – III: Dibenzo (b, f) (1,4) thiazepine-11 (10H)-one (QUE-1I)is reacted with Pocl3 in presence
of Piperazine to give 11-Piperazinyl-dibenzo(b,f) (1,4)-thiazepine hydrochloride.
Stage – IV: 11-Piperazinyl-dibenzo(b,f) (1,4)-thiazepine hydrochloride is reacts with N-methyl
pyrrolidinone in presence of 2-chloro ethoxy ethanol 11-[4-[2-(2-Hydroxy ethoxy) ethyl]-1-
piperazinyl] dibenzo (b, f) (1, 4) thiazepine hemifumarate (QUE-IV).
Chemical Reaction:
Preparation of Phenyl -2- (-phenylthio)phrnyl carbamate (QUE-1)
NH2
S
NHCOOPh
S
2-Aminodiphenyl sulphide
+ C6H5-O-C-Cl
O
Na2CO3
Phenyl-2-(phenylthio)phenyl carbamate
Preparation of Dibenzo (b, f) (1,4) thiazepine-11 (10H)-one (QUE-1I)
S
NO
Polyphosphoric acid
Dibenzo [b,f][1,4]thiazepine-11(10-H)one
HNHCOOPh
S
Phenyl-2-(phenylthio)phenyl carbamate
Preparation of 11-Piperazinyl-dibenzo(b,f) (1,4)-thiazepine hydrochloride (QUE-III HCl):
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Preparation of 11-[4-[2-(2-Hydroxy ethoxy) ethyl]-1-piperazinyl] dibenzo (b, f) (1, 4) thiazepine
hemifumarate (QUE-IV).:
Material Balance:
Stage-I: Preparation of Phenyl-2-(phenyl thio) phenyl carbamate (QUE-1):
Stage-II: Preparation of Dibenzo (b, f) (1,4) thiazepine-11 (10H)-one (QUE-1I)
Stage-III: Preparation of 11-Piperazinyl-dibenzo (b,f) (1,4)-thiazepine hydrochloride (QUE-III)
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Stage- IV: Preparation of 11-[4-[2-(2-Hydroxy ethoxy) ethyl]-1-piperazinyl] dibenzo (b, f) (1, 4)
thiazepine hemifumarate (QUE-IV)
22. 2-[(4-(3-methoxypropoxy)-3-methyl- 2-pyridinyl) methyl]thio]-1H-benzimidazole
Stage – I: 2,3-Dimethyl-4-nitropyridine-N-oxide is reacted with dry HCl and isopropyl alcohol to
give 4-chloro-2,3-dimethylpyridine-N-oxide hydrochloride.
Chemical Reaction:
Stage – II: 4-Chloro-2,3-dimethylpyridine-N-oxide hydrochloride is condensed with 3-methoxy-1-
propanol and rearranged with acetic anhydride and is hydrolyzed with sodium hydroxide and is
neutralized with dry HCl to give 2-hydroxymethyl-4-(3-methoxypropoxy)-3-methylpyridine
hydrochloride.
Chemical Reaction:
Stage – III: 2-Hydroxymethyl-4-(3-methoxypropoxy)-3-methylpyridine hydrochloride is reacted with
thionyl chloride to give 2-chloromethyl-4-(3-methoxypropoxy)-3-methylpyridine hydrochloride.
Chemical Reaction:
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Madhvas, Tal. Kalol, Dist.: Panchmahal
M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 44
Stage – IV: 2-Chloromethyl-4-(3-methoxypropoxy)-3-methylpyridine hydrochloride is condensed
with 2-mercapto-1H-benzimidazole to give 2-[[(4-(3-methoxypropoxy)-3-methyl- 2-pyridinyl)methyl]
thio]-1H-benzimidazole.
Chemical Reaction:
Material Balance:
23. 2-[4-(3-methoxypropoxy)-3-methyl-2-pyridinyl]methyl]sulfinyl]-1H-benzimidazole
Process:
Stage – I: 2,3-Dimethyl-4-nitropyridine-N-oxide is reacted with dry HCl and isopropyl alcohol to
give 4-chloro-2,3-dimethylpyridine-N-oxide hydrochloride.
M/s. Ishanga Life Science Pvt. Ltd.
Madhvas, Tal. Kalol, Dist.: Panchmahal
M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 45
Chemical Reaction:
Stage – II: 4-Chloro-2,3-dimethylpyridine-N-oxide hydrochloride is condensed with 3-methoxy-1-
propanol and rearranged with acetic anhydride and is hydrolyzed with sodium hydroxide and is
neutralized with dry HCl to give 2-hydroxymethyl-4-(3-methoxypropoxy)-3-methylpyridine
hydrochloride.
Chemical Reaction:
Stage – III: 2-Hydroxymethyl-4-(3-methoxypropoxy)-3-methylpyridine hydrochloride is reacted with
thionyl chloride to give 2-chloromethyl-4-(3-methoxypropoxy)-3-methylpyridine hydrochloride.
Chemical Reaction:
Stage – IV: 2-Chloromethyl-4-(3-methoxypropoxy)-3-methylpyridine hydrochloride is condensed
with 2-mercapto-1H-benzimidazole to give 2-[[(4-(3-methoxypropoxy)-3-methyl- 2-pyridinyl)methyl]
thio]-1H-benzimidazole.
Chemical Reaction:
Stage–V: 2-[[(4-(3-Methoxypropoxy)-3-methyl-2-pyridinyl)-2-methyl]thio]-1H-benzimidazole
oxidized to give 2-[[[4-(3-methoxypropoxy)-3-methyl-2-pyridinyl]methyl]sulfinyl]-1H-benzimidazole
Chemical Reaction:
M/s. Ishanga Life Science Pvt. Ltd.
Madhvas, Tal. Kalol, Dist.: Panchmahal
M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 46
Material Balance:
M/s. Ishanga Life Science Pvt. Ltd.
Madhvas, Tal. Kalol, Dist.: Panchmahal
M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 47
ANNEXURE- VII
DETAILS OF WATER CONSUMPTION
DETAILS OF WASTE WATER GENERATION
Category Water Consumption (KLD) Remarks
(A)Domestic 20.0 20.0 KLD Fresh
(B) Gardening 10.0 10.0 KLD Fresh
(C)Industrial
i. Process 85.0 85.0 KLD Recycle
ii. Boiler 30.0 30.0 KLD Fresh
iii. Cooling 40.0 17.0 KLD Fresh + 23.0 KLD Recycle
iv. Washing 27.0 27.0 KLD Recycle
v. Others 10.0 10.0 KLD Recycle - For Scrubber
Industrial Total 192.0 47.0 KLD Fresh + 145.0 KLD Recycle
Total (A+ B +C) 222.0 77.0 KLD Fresh + 145.0 KLD Recycle
Category Wastewater generation(KLD) Remarks
(A) Domestic 15.0 To soak pit
(B) Industrial
i. Process 120.0 Send to ETP for treatment
ii. Boiler 3.0 Send to ETP for treatment
iii. Cooling 2.0 Send to ETP for treatment
iv. Washing 27.0 Send to ETP for treatment
v. Others 10.0 Send to ETP for treatment
Total Industrial
waste water 162.0
Effluent will be treated in ETP and RO
& recycle back in the unit. Unit will
achieve zero liquid discharge.
Total (A + B) 177.0 ------
M/s. Ishanga Life Science Pvt. Ltd.
Madhvas, Tal. Kalol, Dist.: Panchmahal
M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 48
DETAILS OF WATER BALANCE DIAGRAM
Water recycles in
Process+ Washing + Cooling
Recycle
water
Total Water Consumption
222.0 KLD
(77.0 KLD Fresh + 145.0 KLD Recycle)
Process 85.0 KLD (R)
Gardening
10 KLD (F)
Boiler 30.0 KLD (F)
Cooling Total- 40.0 KLD
17.0 (F) + 23.0 (R)
Washing 27.0 KLD (R)
Scrubber 10.0 KLD (R)
Total Industrial – 192.0
47.0 KLD (F) + 145.0 KLD (R)
Effluent 120.0 KLD
Boiler B. D. 3.0 KLD
Cooling tower 2.0 KLD
Total Effluent generation
162.0 KLD
27.0 KLD 10.0 KLD
Solvent stripper
Send for co-processing
7.0 KLD
To ETP for Treatment
To RO Plant RO Reject
50 KLD
Send to MEE
50.0 KLD
Condensate
40.0 KLD
155.0 KLD
155.0 KLD
Salt
10.0 KLD
RO Permeate
105 KLD
Domestic
20 KLD (F)
To Soak Pit
Sewage Effluent
15 KLD
Recycle
water
M/s. Ishanga Life Science Pvt. Ltd.
Madhvas, Tal. Kalol, Dist.: Panchmahal
M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 49
ANNEXURE-VIII
DETAILS OF ELECTRICITY AND FUEL CONSUMPTIONS
ANNEXURE- IX
DETAILS OF FLUE GAS EMISSIONS
Stack
No. Stack Attached to
Fuel
Consumption
Stack
Height (m) APCM Parameter
Permissible
Limit
1. Boiler (3 TPH) Bio-coal/Coal
7.0 MT/Day 11.0
Multi cyclone
separator &
bag filter Particulate
Matter
SO2
NOx
150
mg/Nm3
100 ppm
50 ppm 2.
D. G. Set
(Capacity-600
KVA)
Emergency case
only
Diesel
80 Lit/hr 9.0
Adequate
stack height
ANNEXURE- X
DETAILS OF PROCESS EMISSION
Stack
No. Stack Attached to
Stack
Height (m) APCM Parameter
Permissible
Limit
1. Reactor- I 11.0 2 Stage Water
scrubber Ammonia 175 mg/ Nm
3
2. Reactor - II 11.0 Alkali scrubber Chlorine 9.0 mg/ Nm3
3. Reactor – III 11.0 Alkali scrubber HCl
NOx
20.0 mg/ Nm3
50 ppm
Sr.
No. Particulars Proposed Quantity Remark Source
1.
Bio-coal
(Coal-in case of non
availability of bio-coal during
monsoon)
7.0 MT/day 3 ton boiler considered at
40% load Local
2. Electricity 750 KVA On peak load MGVCL
3. Saw dust 4.5 MT/day Alternate fuel for Boiler Local
4. Diesel 80 Lit/Hr Use for DG set in
emergency case Local
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ANNEXURE- XI
DETAILS OF HAZARDOUS WASTE
Sr.
No. Type of Wastes Category
Source of
Generation
Quantity
MT/Annum Mode of disposal
1 ETP Waste 34.3 Effluent
Treatment 7115.0
Collection, Storage within premises,
Transportation and Disposal at TSDF of
NECL, Nandesari
2 Used Oil 5.1
Maintenance and
used lubricant oil
generated from
Maintenance
Activities
0.400
Collection and Storage within premises
& Disposal by selling to registered re-
processor.
3 Discarded Containers/
Bags/Liners 33.3 Packing Materials 100.0
Collection, Storage and Decontamination
within premises & Disposal by selling to
authorized re-cycler.
4 Process Residue 28.1 Process 8415.0 Collection, Storage, Transportation and
Selling to authorize recycler/NECL.
5 Spent Carbon 28.3
Process 25.0 Collection, Storage, transportation and
send for co-processing to NECL. ETP 24.0
6 Spent catalyst 28.2 Process 1650.0
Collection, Storage within premises,
Transportation and Disposal at TSDF of
NECL/ sent to recycler for activation.
7. Scrubber solution --- Process 3000 Collection, Storage and send to ETP for
treatment.
8. Stripper solvent 28.6 Effluent
Treatment 2520
Collection, storage and send for solvent
recovery/ co-processing/ solvent
recovery
9. MEE Salt 37.3 MEE 3600.0
Collection, Storage within premises,
Transportation and Disposal at TSDF of
NECL.
10 Used membranes --- RO Plant 2.0 Collection, Storage, transportation and
send for land filling to NECL.