Diisopropyl Ether → Ethyl 2-[6-(3-amino-1-pyrrolidinyl)-2-(2,4-difluorophenylamino)-5-fluoronicotinoyl]acetate

HRID 246945Notes

Reaction equation

HRID 246945 reaction equation
Cl[C:2]1[C:15]([F:16])=[CH:14][C:5]([C:6]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])=[O:7])=[C:4]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=2[F:25])[N:3]=1.Cl.Cl.[NH2:28][CH:29]1[CH2:33][CH2:32][NH:31][CH2:30]1.C(N(CC)CC)C.C(OC(C)C)(C)C>C(Cl)(Cl)Cl.O>[NH2:28][CH:29]1[CH2:33][CH2:32][N:31]([C:2]2[C:15]([F:16])=[CH:14][C:5]([C:6]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])=[O:7])=[C:4]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=3[F:25])[N:3]=2)[CH2:30]1

Participants

7

Reactant 4

HCID 7914Diisopropyl EtherHCID 8471TriethylamineHCID 13849316Ethyl 2-[6-chloro-2-(2,4-difluorophenylamino)-5-fluoronicotinoyl]acetateHCID 162125963-Aminopyrrolidine dihydrochloride

Product 1

HCID 13922528Ethyl 2-[6-(3-amino-1-pyrrolidinyl)-2-(2,4-difluorophenylamino)-5-fluoronicotinoyl]acetateYield 84.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6212ChloroformSolvent2×

Procedure

In 5 ml of chloroform was dissolved 500 mg of ethyl 2-[6-chloro-2-(2,4-difluorophenylamino)-5-fluoronicotinoyl]acetate, and 260 mg of 3-aminopyrrolidine dihydrochloride and 500 mg of triethylamine were added thereto, after which the resulting mixture was subjected to reaction under reflux for 1.5 hours. Subsequently, the reaction mixture was added to a mixture of 5 ml of chloroform and 5 ml of water, and the organic layer was separated, washed successively with 5 ml of water and 5 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 2 ml of diisopropyl ether, after which crystals were collected by filtration to obtain 480 mg (yield 84.7%) of ethyl 2-[6-(3-amino-1-pyrrolidinyl)-2-(2,4-difluorophenylamino)-5-fluoronicotinoyl]acetate having a melting point of 140°-142° C.

Workup

  1. additionwere added
  2. customafter which the resulting mixture was subjected to reaction
  3. temperatureunder reflux for 1.5 hours
  4. customthe organic layer was separated
  5. washwashed successively with 5 ml of water and 5 ml of saturated aqueous sodium chloride solution
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customThe solvent was removed by distillation under reduced pressure
  8. customto the crystalline material thus obtained
  9. filtrationafter which crystals were collected by filtration

Sources & evidence

ORD record
ord-5550a47352a2480d88e1226cfc20cb93
Source dataset
uspto-grants-1987_11
Patent number
US04704459

Reaction notes

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