Sodium borohydride → N-((R)-1-(3-(3-chloro-4-cyano-2-methylphenyl)-1H-pyrazol-1-yl)butan-2-yl)-2-(1-hydroxyethyl)thiazole-4-carboxamide

HRID 872696Notes

Reaction equation

HRID 872696 reaction equation
[BH4-].[Na+].[C:3]([C:6]1[S:7][CH:8]=[C:9]([C:11]([NH:13][C@H:14]([CH2:31][CH3:32])[CH2:15][N:16]2[CH:20]=[CH:19][C:18]([C:21]3[CH:26]=[CH:25][C:24]([C:27]#[N:28])=[C:23]([Cl:29])[C:22]=3[CH3:30])=[N:17]2)=[O:12])[N:10]=1)(=[O:5])[CH3:4]>C(O)C>[Cl:29][C:23]1[C:22]([CH3:30])=[C:21]([C:18]2[CH:19]=[CH:20][N:16]([CH2:15][C@H:14]([NH:13][C:11]([C:9]3[N:10]=[C:6]([CH:3]([OH:5])[CH3:4])[S:7][CH:8]=3)=[O:12])[CH2:31][CH3:32])[N:17]=2)[CH:26]=[CH:25][C:24]=1[C:27]#[N:28]

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 67173515(R)-2-acetyl-N-(1-(3-(3-chloro-4-cyano-2-methylphenyl)-1H-pyrazol-1-yl)-butan-2-yl)thiazole-4-carboxamide

Product 1

HCID 70656705N-((R)-1-(3-(3-chloro-4-cyano-2-methylphenyl)-1H-pyrazol-1-yl)butan-2-yl)-2-(1-hydroxyethyl)thiazole-4-carboxamideYield 74.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Sodium borohydride (7.19 mg, 0.190 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. (R)-2-acetyl-N-(1-(3-(3-chloro-4-cyano-2-methylphenyl)-1H-pyrazol-1-yl)butan-2-yl)thiazole-4-carboxamide (42 mg, 0.095 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 to about 3 and the mixture was evaporated. 5% DCM/MeOH was added and the crude product was washed with 1M NaHCO3, water and dried. Yield 74.2%. 1H-NMR (400 MHz; CDCl3): δ 1.03 (m, 3H), 1.56-1.59 (m, 3H), 2.54 & 2.55 (2× broad s, 3H), 4.34-4.46 (m, 3H), 5.07 (dd, 1H), 6.41-6.43 (m, 1H), 7.46-7.54 (m, 3H), 7.80-7.89 (m, 1H), 8.02 (s, 1H).

Workup

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

Sources & evidence

ORD record
ord-d04b1215fc4541e394a1371ee23df9c6
Source dataset
uspto-grants-2015_03
Patent number
US08975254B2

Reaction notes

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