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Chloroform → Methyl 6-(3-amino-1-pyrrolidinyl)-2-(2,4-difluorophenylamino)-5-fluoronicotinate

HRID 232453
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인쇄 미리보기

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HRID 232453 반응식
Cl[C:2]1[C:11]([F:12])=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=2[F:21])[N:3]=1.Cl.Cl.[NH2:24][CH:25]1[CH2:29][CH2:28][NH:27][CH2:26]1.C(N(CC)CC)C.C(Cl)(Cl)Cl>CN(C)C=O.C(OCC)C.O>[NH2:24][CH:25]1[CH2:29][CH2:28][N:27]([C:2]2[C:11]([F:12])=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=3[F:21])[N:3]=2)[CH2:26]1
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

8

반응물 4

HCID 6212ChloroformHCID 8471TriethylamineHCID 13849310Methyl 6-chloro-2-(2,4-difluorophenylamino)-5-fluoronicotinateHCID 162125963-Aminopyrrolidine dihydrochloride

생성물 1

HCID 13821762Methyl 6-(3-amino-1-pyrrolidinyl)-2-(2,4-difluorophenylamino)-5-fluoronicotinate수율 95.1%

시약·촉매·용매 3

HCID 962
Water
용매
HCID 3283Diethyl Ether용매
HCID 6228Dimethylformamide용매

실험 절차

In 10 ml of N,N-dimethylformamide was suspended 1.00 g of methyl 6-chloro-2-(2,4-difluorophenylamino)-5-fluoronicotinate, and to the resulting suspension were added 750 mg of 3-aminopyrrolidine dihydrochloride, and 1.44 g of triethylamine, after which the resulting mixture was subjected to reaction at 70° C. for 30 minutes. Subsequently, to the reaction mixture were added 50 ml of chloroform and 50 ml of water, and the organic layer was separated, washed successively with 25 ml of water and 25 ml of saturated aqueous sodium chloride solution, and then dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure, and to the crystalline material thus obtained was added 5 ml of diethyl ether, after which crystals were collected by filtration to obtain 1.10 g (yield 95.1%) of methyl 6-(3-amino-1-pyrrolidinyl)-2-(2,4-difluorophenylamino)-5-fluoronicotinate having a melting point of 139°-140° C.

후처리

  1. customafter which the resulting mixture was subjected to reaction at 70° C. for 30 minutes
  2. customthe organic layer was separated
  3. washwashed successively with 25 ml of water and 25 ml of saturated aqueous sodium chloride solution
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customThe solvent was removed by distillation under reduced pressure
  6. customto the crystalline material thus obtained
  7. filtrationafter which crystals were collected by filtration

출처 및 근거

ORD 기록
ord-e5569e6b804447a08b36a57d3bc5c337
출처 데이터셋
uspto-grants-1989_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US04851535

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