Hydrochloric Acid → N-((S)-1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-2-(1-hydroxyethyl)thiazole-4-carboxamide

HRID 872855Notes

Reaction equation

HRID 872855 reaction equation
[C:1]([C:4]1[S:5][CH:6]=[C:7]([C:9]([NH:11][C@@H:12]([CH3:28])[CH2:13][N:14]2[CH:18]=[CH:17][C:16]([C:19]3[CH:24]=[CH:23][C:22]([C:25]#[N:26])=[C:21]([Cl:27])[CH:20]=3)=[N:15]2)=[O:10])[N:8]=1)(=[O:3])[CH3:2].[BH4-].[Na+].O.Cl>C(O)C>[Cl:27][C:21]1[CH:20]=[C:19]([C:16]2[CH:17]=[CH:18][N:14]([CH2:13][C@@H:12]([NH:11][C:9]([C:7]3[N:8]=[C:4]([CH:1]([OH:3])[CH3:2])[S:5][CH:6]=3)=[O:10])[CH3:28])[N:15]=2)[CH:24]=[CH:23][C:22]=1[C:25]#[N:26]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 4311764Sodium borohydrideHCID 67172874(S)-2-acetyl-N-(1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)thiazole-4-carboxamide

Product 1

HCID 70655948N-((S)-1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-2-(1-hydroxyethyl)thiazole-4-carboxamideYield 41.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Into a flask containing (S)-2-acetyl-N-(1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)thiazole-4-carboxamide (1 g, 2.416 mmol) dissolved in ethanol (10 ml), sodium borohydride (0.137 g, 3.62 mmol) was added in small parts under nitrogen atmosphere. The following mixture was stirred overnight in RT. Next morning water (1 ml) was added dropwise and the pH of the mixture was adjusted to under 7 with 1 M HCl and the mixture was evaporated. 30 ml of ethyl acetate was added and stirred for 30 min, filtered and the filtrate was evaporated and dried in vacuum at 40° C. The product was purified by recrystallizing it twice from diethyl ether/ethanol to yield 41.6% of the title compound. 1H-NMR (400 MHz; DMSO-d6): δ 1.10-1.16 (m, 3H), 1.44-1.48 (m, 3H), 4.29-4.52 (m, 3H), 4.94-4.02 (m, 3H), 6.22-6.26 (m, 1H), 6.95-6.99 (m, 1H), 7.83-7.88 (m, 1H), 7.93-8.00 (m, 2H), 8.07-8.10 (m, 1H), 8.11 (d, 1H), 8.33-4.39 (m, 1H).

Workup

  1. customthe mixture was evaporated
  2. addition30 ml of ethyl acetate was added
  3. stirringstirred for 30 min
  4. filtrationfiltered
  5. customthe filtrate was evaporated
  6. customdried in vacuum at 40° C
  7. customThe product was purified
  8. customby recrystallizing it twice from diethyl ether/ethanol

Sources & evidence

ORD record
ord-79e31ef66cdb475081f496d159dc81dc
Source dataset
uspto-grants-2015_03
Patent number
US08975254B2

Reaction notes

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