Water → HCID 178513576, compound

HRID 2247157Notes

Reaction equation

HRID 2247157 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8](O)[C:9]2[CH:14]=[CH:13][C:12]([C:15]3[NH:19][C:18]4[CH:20]=[CH:21][C:22]([C:24]([NH2:26])=[O:25])=[CH:23][C:17]=4[N:16]=3)=[CH:11][CH:10]=2)=[CH:4][CH:3]=1.[BH4-].[Na+].O.[OH-].[Na+]>C(O)(C(F)(F)F)=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C:9]2[CH:10]=[CH:11][C:12]([C:15]3[NH:19][C:18]4[CH:20]=[CH:21][C:22]([C:24]([NH2:26])=[O:25])=[CH:23][C:17]=4[N:16]=3)=[CH:13][CH:14]=2)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 4311764Sodium borohydrideHCID 178513581HCID 178513581, compound

Product 1

HCID 178513576HCID 178513576, compoundYield 82.9%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

To a solution of 2-{4-[(4-chloro-phenyl)-hydroxy-methyl]-phenyl}-1-H-benzoimidazole-5-carboxylic acid amide (Example 20, 50 mg, 0.13 mmol) in TFA (5.0 mL) was added sodium borohydride (211 mg, 4.2 equiv), and the reaction mixture was stirred at RT for 16 h. Water (5.0 mL) was added to the mixture, which was then adjusted to pH 9 with 1 N NaOH. The precipitate was collected by filtration and washed with H2O (20 mL). Purification by chromatography (silica gel, 1% methanol saturated with ammonia/9% methanol/CH2Cl2) afforded 39 mg (81%) of the title compound. HPLC (Method A): Rt=7.64. MS (ESI+): mass calculated for C21H16ClN3O, 361.1; m/z found, 362.2 [M+H]+. 1H NMR (500 MHz, CD3OD): δ 8.23 (d, J=1.4 Hz, 1H), 8.06 (d, J=8.2 Hz, 2H), 7.94-7.92 (dd, J=8.5, 1.6 Hz, 1H), 7-0.74 (d, J=8.5 Hz, 1H), 7.48 (d, J=8.2 Hz, 2H), 7.31 (d, J=8.4 Hz, 2H), 7.25 (d, J=8.4 Hz, 2H), 4.09 (s, 2H).

Workup

  1. filtrationThe precipitate was collected by filtration
  2. washwashed with H2O (20 mL)
  3. customPurification by chromatography (silica gel, 1% methanol saturated with ammonia/9% methanol/CH2Cl2)

Sources & evidence

ORD record
ord-3ab56bf7e5684c99bf13fbda3f42d69a
Source dataset
uspto-grants-2010_03
Patent number
US07687639B2

Reaction notes

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