Acetaldehyde → 3-{2-[(2,4-Dichlorophenyl)amino]-7-(diethylamino)-1H-benzimidazol-1-yl}-2,2-difluoropropan-1-ol

HRID 1628523Notes

Reaction equation

[NH2:1][C:2]1[C:7]2[N:8]([CH2:20][C:21]([F:25])([F:24])[CH2:22][OH:23])[C:9]([NH:11][C:12]3[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:13]=3[Cl:19])=[N:10][C:6]=2[CH:5]=[CH:4][CH:3]=1.[CH:26](=O)[CH3:27].[C:29](O[BH-](OC(=O)C)OC(=O)C)(=O)[CH3:30].[Na+]>CO.C(O)(=O)C.O>[Cl:19][C:13]1[CH:14]=[C:15]([Cl:18])[CH:16]=[CH:17][C:12]=1[NH:11][C:9]1[N:8]([CH2:20][C:21]([F:24])([F:25])[CH2:22][OH:23])[C:7]2[C:2]([N:1]([CH2:26][CH3:27])[CH2:29][CH3:30])=[CH:3][CH:4]=[CH:5][C:6]=2[N:10]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 3-{7-amino-2-[(2,4-dichlorophenyl)amino]-1H-benzimidazol-1-yl}-2,2-difluoropropan-1-ol (51.0 mg, 0.132 mmol) in methanol (1.3 mL) and acetic acid (26 μL) was added acetaldehyde (49 μL, 0.790 mmol) at 0° C. The mixture was stirred at 0° C. for 30 min. To the reaction mixture was added sodium triacetoxyborohydride (176.2 mg, 0.790 mmol) at 0° C. After 1 hr, the mixture was diluted with water and extracted with ethyl acetate (×3). The combined organic layer was washed with brine (×1), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with a 0-30% ethyl acetate/n-hexane gradient mixture to give the title compound as an amorphous (49.8 mg, 0.112 mmol, 85%).

Workup

waitAfter 1 hr
extractionextracted with ethyl acetate (×3)
washThe combined organic layer was washed with brine (×1)
dry with materialdried over anhydrous magnesium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was purified by silica gel column chromatography
washeluting with a 0-30% ethyl acetate/n-hexane gradient mixture

Sources & evidence

ORD record: ord-51de46a5d2ec411e91ee54464c50c8a2
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08785460B2

Reaction notes

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