Acetic Acid → HCID 11996233, compound

HRID 1092209Notes

Reaction equation

[NH2:1][CH2:2][C:3]1[C:4]([NH:20][C@H:21]([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)[CH3:22])=[CH:5][C:6]2[N:10]([C:11]3[CH:15]=[C:14]([CH:16]4[CH2:18][CH2:17]4)[NH:13][N:12]=3)[CH:9]=[N:8][C:7]=2[CH:19]=1.[C:30](O)(=[O:32])[CH3:31]>C1COCC1.C(Cl)Cl>[CH:16]1([C:14]2[NH:13][N:12]=[C:11]([N:10]3[C:6]4[CH:5]=[C:4]([NH:20][C@H:21]([C:23]5[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=5)[CH3:22])[C:3]([CH2:2][NH:1][C:30](=[O:32])[CH3:31])=[CH:19][C:7]=4[N:8]=[CH:9]3)[CH:15]=2)[CH2:18][CH2:17]1

Participants

Conditions

Temperature: 0 °C

Procedure

A round bottom flask was charged with 6-(aminomethyl)-3-(5-cyclopropyl-1H-pyrazol-3-yl)-N-((S)-1-(4-fluorophenyl)ethyl)-3H-benzo[d]imidazol-5-amine (Example 42; 0.10 g, 0.256 mmol) and acetic acid loaded TFP resin (1.0 mmol/g loading, 0.256 g, 0.256 mmol) in mixture of THF-DCM (1:1, 3 ml) at 0° C. The resulting solution was stirred vigorously at 0° C. for 1 hour and filtered through a Jones tube. The resulting resin was washed with a THF-DCM solution (1:1, 3×5 ml). After removal of solvent, the residue was purified by column chromatography (EtOAc-MeOH=20:1) to give the title compound as an off-white solid (0.083 g, 75%). 1H NMR (400 MHz) 12.67 (s, 1H), 8.50 (m, 1H), 8.18 (s, 1H), 7.39 (m, 3H), 7.11 (m, 2H), 6.73 (s, 1H), 6.09 (d, J=6.0 Hz, 1H), 5.96 (s, 1H), 4.53 (m, 1H), 4.42 (m, 1H), 4.31 (m, 1H), 1.93 (m, 1H), 1.93 (s, 3 h), 1.47 (d, J=6.4 Hz, 3H), 1.02 (m, 2H), 0.76 (m, 2H). MS: Calcd.: 432; Found: [M+H]+ 433.

Workup

filtrationfiltered through a Jones tube
washThe resulting resin was washed with a THF-DCM solution (1:1, 3×5 ml)
customAfter removal of solvent
customthe residue was purified by column chromatography (EtOAc-MeOH=20:1)

Sources & evidence

ORD record: ord-0e9a97e22f0b412f884e2157c47ca087
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08129403B2

Reaction notes

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