Triethylamine → 3-{7-Amino-2-[(2,4-dichlorophenyl)amino]-1H-benzimidazol-1-yl}-2,2-difluoropropan-1-ol

HRID 1398879Notes

Reaction equation

[NH2:1][C:2]1[C:3]([NH:20][CH2:21][C:22]([F:26])([F:25])[CH2:23][OH:24])=[C:4]([NH:8][C:9]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:13]=2[Cl:19])=S)[CH:5]=[CH:6][CH:7]=1.C(N(CC)CC)C.Cl.C(N=C=NCCCN(C)C)C>O1CCCC1.O>[NH2:1][C:2]1[C:3]2[N:20]([CH2:21][C:22]([F:26])([F:25])[CH2:23][OH:24])[C:9]([NH:11][C:12]3[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:13]=3[Cl:19])=[N:8][C:4]=2[CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 50 °C

Procedure

To a mixture of 1-{3-amino-2-[(2,2-difluoro-3-hydroxypropyl)amino]phenyl}-3-(2,4-dichlorophenyl)thiourea (65.0 mg, 0.154 mmol) in tetrahydrofuran (1.5 mL) were added triethylamine (23.4 μL, 0.169 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (29.6 mg, 0.154 mmol). The mixture was stirred at 50° C. for 3 hrs. After cooling, the mixture was diluted with water, extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with a 0-40% ethyl acetate/n-hexane gradient mixture to give the title compound as an amorphous (53.0 mg, 0.137 mmol, 89%).

Workup

temperatureAfter cooling
extractionextracted with ethyl acetate
washThe combined organic layer was washed with brine
dry with materialdried over anhydrous magnesium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was purified by silica gel column chromatography
washeluting with a 0-40% ethyl acetate/n-hexane gradient mixture

Sources & evidence

ORD record: ord-45b400cd39594e56835a54dd02f3965d
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08901141B2

Reaction notes

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