Sodium borohydride → N-((S)-1-(3-(3-chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-5-(1-hydroxyethyl)isoxazole-3-carboxamide

HRID 872707Notes

Reaction equation

HRID 872707 reaction equation
[BH4-].[Na+].[C:3]([C:6]1[O:10][N:9]=[C:8]([C:11]([NH:13][C@@H:14]([CH3:31])[CH2:15][N:16]2[CH:20]=[CH:19][C:18]([C:21]3[CH:26]=[C:25]([F:27])[C:24]([C:28]#[N:29])=[C:23]([Cl:30])[CH:22]=3)=[N:17]2)=[O:12])[CH:7]=1)(=[O:5])[CH3:4]>C(O)C>[Cl:30][C:23]1[CH:22]=[C:21]([C:18]2[CH:19]=[CH:20][N:16]([CH2:15][C@@H:14]([NH:13][C:11]([C:8]3[CH:7]=[C:6]([CH:3]([OH:5])[CH3:4])[O:10][N:9]=3)=[O:12])[CH3:31])[N:17]=2)[CH:26]=[C:25]([F:27])[C:24]=1[C:28]#[N:29]

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 52919950(S)-5-acetyl-N-(1-(3-(3-chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)isoxazole-3-carboxamide

Product 1

HCID 70656673N-((S)-1-(3-(3-chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-5-(1-hydroxyethyl)isoxazole-3-carboxamideYield 81%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Sodium borohydride (0.012 g, 0.308 mmol) was added into a flask and the atmosphere was replaced with nitrogen. Dry ethanol was added and the reaction mixture was cooled to 0° C. (S)-5-acetyl-N-(1-(3-(3-chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)isoxazole-3-carboxamide (0.064 g, 0.154 mmol) was added and the reaction mixture was warmed slowly to RT while stirring overnight. The crude product was cooled to 0° C., the pH was adjusted below 7 and the mixture was evaporated. 5% of DCM/MeOH was added and the crude product was washed with 1M NaHCO3, water and dried. Yield 81%. 1H-NMR (400 MHz; DMSO-d6): δ 1.16 (d, 3H), 1.40 (dd, 3H), 4.32 (d, 2H), 4.45 (m, 1H), 4.86 (m, 1H), 5.78 (dd, 1H), 6.53 (dd, 1H), 7.00 (d, 1H), 7.84 (d, 1H), 7.86 (m, 1H), 7.98 (d, 1H), 8.75 (d, 1H).

Workup

  1. additionwas added
  2. customthe mixture was evaporated
  3. addition5% of DCM/MeOH was added
  4. washthe crude product was washed with 1M NaHCO3, water
  5. customdried

Sources & evidence

ORD record
ord-484006a780db4fd2b3c905a1d1684e62
Source dataset
uspto-grants-2015_03
Patent number
US08975254B2

Reaction notes

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