Lithium Hydroxide → 2-{[(1S)-1-(5-Fluoropyrimidin-2-yl)ethyl]amino}-6-[(5-methyl-1H-pyrazol-3-yl)amino]-5-nitropyrimidine-4-carboxylic acid

HRID 450388Notes

Reaction equation

HRID 450388 reaction equation
[F:1][C:2]1[CH:3]=[N:4][C:5]([C@@H:8]([NH:10][C:11]2[N:16]=[C:15]([C:17]([O:19]CC)=[O:18])[C:14]([N+:22]([O-:24])=[O:23])=[C:13]([NH:25][C:26]3[CH:30]=[C:29]([CH3:31])[NH:28][N:27]=3)[N:12]=2)[CH3:9])=[N:6][CH:7]=1.[Li+].[OH-]>C1COCC1.CO.O>[F:1][C:2]1[CH:3]=[N:4][C:5]([C@@H:8]([NH:10][C:11]2[N:16]=[C:15]([C:17]([OH:19])=[O:18])[C:14]([N+:22]([O-:24])=[O:23])=[C:13]([NH:25][C:26]3[CH:30]=[C:29]([CH3:31])[NH:28][N:27]=3)[N:12]=2)[CH3:9])=[N:6][CH:7]=1

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 68781144Ethyl 2-{[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]amino}-6-[(5-methyl-1H-pyrazol-3-yl)amino]-5-nitropyrimidine-4-carboxylate2×

Product 1

HCID 687821322-{[(1S)-1-(5-Fluoropyrimidin-2-yl)ethyl]amino}-6-[(5-methyl-1H-pyrazol-3-yl)amino]-5-nitropyrimidine-4-carboxylic acidYield 50.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 21899815MeOH tetrahydrofuranSolvent

Procedure

To a solution of ethyl 2-{[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]amino}-6-[(5-methyl-1H-pyrazol-3-yl)amino]-5-nitropyrimidine-4-carboxylate (Intermediate 49, 2 mmol) in THF/MeOH (1:1 v/v, 10 ml) was added LiOH (0.42 g) in H2O (1 ml) and the resulting mixture was stirred at ambient temperature overnight. The volatiles were evaporated under reduced pressure and the solid left was diluted with H2O. The aqueous layer was acidified with 1N HCl (aq) solution and extracted with EtOAc (3×). The combined organic layers were dried and evaporation gave the title compound (406 mg), used in the next step without further purification. LCMS: 402 [M−1].

Workup

  1. customThe volatiles were evaporated under reduced pressure
  2. waitthe solid left
  3. additionwas diluted with H2O
  4. extractionextracted with EtOAc (3×)
  5. customThe combined organic layers were dried
  6. customevaporation

Sources & evidence

ORD record
ord-88357979306946a7ae2a47e9227ed932
Source dataset
uspto-grants-2013_07
Patent number
US08486966B2

Reaction notes

Loading…