Sodium Bicarbonate → 4-chloro-N-[(4-chloro-3-{[3-cyano-5-(hydroxymethyl)phenyl]oxy}-2-fluorophenyl)methyl]-2-methyl-1H-imidazole-5-carboxamide

HRID 1875175Notes

Reaction equation

HRID 1875175 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([CH3:30])[NH:5][C:6]=1[C:7]([NH:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([O:18][C:19]2[CH:24]=[C:23]([CH:25]=[O:26])[CH:22]=[C:21]([C:27]#[N:28])[CH:20]=2)[C:12]=1[F:29])=[O:8].[BH4-].[Na+].C(=O)(O)[O-].[Na+]>CO.CCOC(C)=O>[Cl:1][C:2]1[N:3]=[C:4]([CH3:30])[NH:5][C:6]=1[C:7]([NH:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([O:18][C:19]2[CH:24]=[C:23]([CH2:25][OH:26])[CH:22]=[C:21]([C:27]#[N:28])[CH:20]=2)[C:12]=1[F:29])=[O:8]

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 178432877HCID 178432877, compound

Product 1

HCID 1784328784-chloro-N-[(4-chloro-3-{[3-cyano-5-(hydroxymethyl)phenyl]oxy}-2-fluorophenyl)methyl]-2-methyl-1H-imidazole-5-carboxamideYield 76%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-chloro-N-({4-chloro-3-[(3-cyano-5-formylphenyl)oxy]-2-fluorophenyl}methyl)-2-methyl-1H-imidazole-5-carboxamide (0.178 g, 0.398 mmol) in methanol (5 ml) at 0° C. was added sodium borohydride (0.015 g, 0.398 mmol) and the reaction mixture was allowed to warm to rt over 30 minutes. The reaction mixture was neutralized with saturated sodium bicarbonate, diluted with EtOAc, and the organic layer was separated. The solvent was evaporated and the crude material was purifed via silica gel chromatography to give 4-chloro-N-[(4-chloro-3-{[3-cyano-5-(hydroxymethyl)phenyl]oxy}-2-fluorophenyl)methyl]-2-methyl-1H-imidazole-5-carboxamide (0.135 g, 0.300 mmol, 76% yield). 1H NMR (400 MHz, METHANOL-d4) δ ppm 7.39 (s, 1H), 7.27-7.38 (m, 2H), 7.18 (s, 1H), 7.08 (s, 1H), 4.60 (s, 2 H), 4.58 (s, 2H), 2.32 (s, 3H). LC-MS (ES+) m/z 448.94, [M+H].

Workup

  1. customthe organic layer was separated
  2. customThe solvent was evaporated

Sources & evidence

ORD record
ord-f22a5af1033b4dbda8741fc1644a9b7b
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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