Water → Ethyl 2-[6-(3-acetylamino-1-pyrrolidinyl)-2-(2,4-difluorophenylamino)-5-fluoronicotinoyl]acetate

HRID 246949Notes

Reaction equation

HRID 246949 reaction equation
[NH2:1][CH:2]1[CH2:6][CH2:5][N:4]([C:7]2[C:20]([F:21])=[CH:19][C:10]([C:11]([CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15])=[O:12])=[C:9]([NH:22][C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:24]=3[F:30])[N:8]=2)[CH2:3]1.[C:31](OC(=O)C)(=[O:33])[CH3:32].O.C(OC(C)C)(C)C>C(Cl)(Cl)Cl>[C:31]([NH:1][CH:2]1[CH2:6][CH2:5][N:4]([C:7]2[C:20]([F:21])=[CH:19][C:10]([C:11]([CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15])=[O:12])=[C:9]([NH:22][C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:24]=3[F:30])[N:8]=2)[CH2:3]1)(=[O:33])[CH3:32]

Participants

6

Reactant 4

HCID 962WaterHCID 7914Diisopropyl EtherHCID 7918Acetic AnhydrideHCID 13922528Ethyl 2-[6-(3-amino-1-pyrrolidinyl)-2-(2,4-difluorophenylamino)-5-fluoronicotinoyl]acetate

Product 1

HCID 13849322Ethyl 2-[6-(3-acetylamino-1-pyrrolidinyl)-2-(2,4-difluorophenylamino)-5-fluoronicotinoyl]acetateYield 72.8%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Procedure

In 1 ml of chloroform was dissolved 100 mg of ethyl 2-[6-(3-amino-1-pyrrolidinyl)-2-(2,4-difluorophenylamino)-5-fluoronicotinoyl]acetate, and 26 mg of acetic anhydride was added thereto, after which the resulting mixture was subjected to reaction at room temperature for 30 minutes. Subsequently, the reaction mixture was added to a mixture of 1 ml of water and 1 ml of chloroform, and the organic layer was separated, washed successively with 1 ml of water and 1 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 0.5 ml of diisopropyl ether, after which crystals were collected by filtration to obtain 80 mg (yield 72.8%) of ethyl 2-[6-(3-acetylamino-1-pyrrolidinyl)-2-(2,4-difluorophenylamino)-5-fluoronicotinoyl]acetate. The physical properties of this compound were identical with those of the compound obtained in Example 19.

Workup

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

Sources & evidence

ORD record
ord-dfa4ae835d1d4e8488122056116f60b2
Source dataset
uspto-grants-1987_11
Patent number
US04704459

Reaction notes

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