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

HRID 246931Notes

Reaction equation

HRID 246931 reaction equation
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

Participants

8

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-63fb17d65bda43c5afff98dad4412b09
Source dataset
uspto-grants-1987_11
Patent number
US04704459

Reaction notes

Loading…