DE2528365A1 - Verfahren zur herstellung von 1,3-bis(2-chloraethyl)-1-nitrosoharnstoff - Google Patents
Verfahren zur herstellung von 1,3-bis(2-chloraethyl)-1-nitrosoharnstoffInfo
- Publication number
- DE2528365A1 DE2528365A1 DE19752528365 DE2528365A DE2528365A1 DE 2528365 A1 DE2528365 A1 DE 2528365A1 DE 19752528365 DE19752528365 DE 19752528365 DE 2528365 A DE2528365 A DE 2528365A DE 2528365 A1 DE2528365 A1 DE 2528365A1
- Authority
- DE
- Germany
- Prior art keywords
- bis
- bcnu
- chloroethyl
- urea
- excess
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 238000000034 method Methods 0.000 title claims description 23
- 230000008569 process Effects 0.000 title claims description 12
- -1 2-CHLORAETHYL Chemical class 0.000 title description 4
- 238000004519 manufacturing process Methods 0.000 title description 3
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 claims description 26
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 20
- 239000002904 solvent Substances 0.000 claims description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- VBWBRZHAGLZNST-UHFFFAOYSA-N 1,3-bis(2-chloroethyl)urea Chemical compound ClCCNC(=O)NCCCl VBWBRZHAGLZNST-UHFFFAOYSA-N 0.000 claims description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 6
- 239000000376 reactant Substances 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 3
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 claims description 3
- GQPLMRYTRLFLPF-UHFFFAOYSA-N Nitrous Oxide Chemical compound [O-][N+]#N GQPLMRYTRLFLPF-UHFFFAOYSA-N 0.000 claims 4
- 239000001272 nitrous oxide Substances 0.000 claims 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 1
- 229910001873 dinitrogen Inorganic materials 0.000 claims 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- 150000001875 compounds Chemical class 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 6
- 239000004202 carbamide Substances 0.000 description 6
- LZDSILRDTDCIQT-UHFFFAOYSA-N dinitrogen trioxide Chemical compound [O-][N+](=O)N=O LZDSILRDTDCIQT-UHFFFAOYSA-N 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 150000002170 ethers Chemical class 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000002329 infrared spectrum Methods 0.000 description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- 150000008065 acid anhydrides Chemical class 0.000 description 2
- 150000001336 alkenes Chemical class 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 239000012456 homogeneous solution Substances 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 150000002690 malonic acid derivatives Chemical class 0.000 description 2
- 150000002828 nitro derivatives Chemical class 0.000 description 2
- OSTGTTZJOCZWJG-UHFFFAOYSA-N nitrosourea Chemical compound NC(=O)N=NO OSTGTTZJOCZWJG-UHFFFAOYSA-N 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-N Nitrous acid Chemical compound ON=O IOVCWXUNBOPUCH-UHFFFAOYSA-N 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000000118 anti-neoplastic effect Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 230000009935 nitrosation Effects 0.000 description 1
- 238000007034 nitrosation reaction Methods 0.000 description 1
- 150000002832 nitroso derivatives Chemical class 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 229910052814 silicon oxide Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/17—Amides, e.g. hydroxamic acids having the group >N—C(O)—N< or >N—C(S)—N<, e.g. urea, thiourea, carmustine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C275/66—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to halogen atoms or to nitro or nitroso groups
- C07C275/68—N-nitroso ureas
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US05/523,334 US4028410A (en) | 1974-11-13 | 1974-11-13 | Process of preparing 1,3-bis(2-chloroethyl)-1-nitrosourea |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2528365A1 true DE2528365A1 (de) | 1976-05-20 |
Family
ID=24084603
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19752528365 Withdrawn DE2528365A1 (de) | 1974-11-13 | 1975-06-25 | Verfahren zur herstellung von 1,3-bis(2-chloraethyl)-1-nitrosoharnstoff |
Country Status (8)
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS56120662A (en) * | 1980-02-28 | 1981-09-22 | Kowa Co | Novel nitrosourea derivative and its preparation |
| JPS57116043A (en) * | 1981-01-12 | 1982-07-19 | Tetsuo Suami | New nitrosourea derivative and its preparation |
| US20040072889A1 (en) * | 1997-04-21 | 2004-04-15 | Pharmacia Corporation | Method of using a COX-2 inhibitor and an alkylating-type antineoplastic agent as a combination therapy in the treatment of neoplasia |
| GB9719426D0 (en) * | 1997-09-13 | 1997-11-12 | Johnson Matthey Plc | Novel process |
| WO2007085026A2 (en) * | 2006-01-20 | 2007-07-26 | The Board Of Regents Of The University Of Texas System | Compositions and methods for the direct therapy of tumors |
| JP6325139B2 (ja) | 2016-03-02 | 2018-05-16 | ネルファルマ・エッセ・エッルレ・エッレ | カルムスチンの安全で効率的な製造方法 |
| WO2017154019A1 (en) * | 2016-03-11 | 2017-09-14 | Msn Laboratories Private Limited | An improved process for the preparation of 1,3-bis(2-chloroethyl)-1-nitrosourea |
| WO2017178910A1 (en) | 2016-04-16 | 2017-10-19 | Intas Pharmaceuticals Ltd. | Process for preparation of carmustine |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3465025A (en) * | 1966-11-17 | 1969-09-02 | Allied Chem | Process for the preparation of isocyanates |
-
1974
- 1974-11-13 US US05/523,334 patent/US4028410A/en not_active Expired - Lifetime
-
1975
- 1975-04-03 GB GB1363475A patent/GB1469381A/en not_active Expired
- 1975-04-23 SE SE7504719A patent/SE7504719L/xx unknown
- 1975-04-29 FR FR7513437A patent/FR2291187A1/fr active Granted
- 1975-05-14 CA CA226,863A patent/CA1082223A/en not_active Expired
- 1975-05-19 JP JP50059538A patent/JPS5156414A/ja active Pending
- 1975-06-25 DE DE19752528365 patent/DE2528365A1/de not_active Withdrawn
- 1975-07-04 CH CH881175A patent/CH598204A5/xx not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| GB1469381A (en) | 1977-04-06 |
| AU8007675A (en) | 1976-10-14 |
| CH598204A5 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1978-04-28 |
| JPS5156414A (en) | 1976-05-18 |
| FR2291187A1 (fr) | 1976-06-11 |
| US4028410A (en) | 1977-06-07 |
| SE7504719L (sv) | 1976-05-14 |
| FR2291187B1 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1980-04-04 |
| CA1082223A (en) | 1980-07-22 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8141 | Disposal/no request for examination |