Water → HCID 136191279, compound
Reaction equation
[Br:1][C:2]1[C:7]2[N:8]=[C:9]([C:11]3[C:12](=[O:28])[NH:13][CH:14]=[CH:15][C:16]=3[NH:17][CH2:18][C@H:19]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[CH:22]=3)[OH:20])[NH:10][C:6]=2[CH:5]=[C:4]([C:29]#N)[CH:3]=1.CC(C[AlH]CC(C)C)C.CC[O:42]C(C)=O.O>C1COCC1>[Br:1][C:2]1[C:7]2[N:8]=[C:9]([C:11]3[C:12](=[O:28])[NH:13][CH:14]=[CH:15][C:16]=3[NH:17][CH2:18][C@H:19]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[CH:22]=3)[OH:20])[NH:10][C:6]=2[CH:5]=[C:4]([CH:29]=[O:42])[CH:3]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- -40 °C
Procedure
To a solution of (S)-7-Bromo-2-{4-[2-(3-chloro-phenyl)-2-hydroxy-ethylamino]-2-oxo-1,2-dihydro-pyridin-3-yl}-3H-benzimidazole-5-carbonitrile (150 mg, 0.31 mmol) in THF (50 mL) was added DIBAL-H (1 M toluene solution, 1.55 mL, 1.55 mmol) at −78° C. The reaction mixture was stirred at −40° C. for 10 h and cooled to −78° C. EtOAc (0.5 mL) was added. The reaction mixture was stirred for 30 min at −78° C. before water (1 mL) was added. The reaction mixture was warmed to room temperature and concentrated. The residue was passed through a small pad of celite. The filtrate was concentrated and purified by prep. HPLC to give the titled compound (67 mg, 43%). 1H NMR (400 MHz, CD3OD) δ 9.45 (1H, s), 7.62 (1H, s), 7.56 (1H, narrow d, J=1.6 Hz), 7.44 (1H, narrow d, J=1.0 Hz), 7.32–7.42 (2H, m), 7.24–7.30 (3H, m), 6.24 (1H, d, J=7.6 Hz), 5.01 (1H, m), 3.65–3.76 (2H, m). LCMS (M+H)+ m/z 487 (t=1.76 min.).
Workup
- temperaturecooled to −78° C
- additionwas added
- temperatureThe reaction mixture was warmed to room temperature
- concentrationconcentrated
- concentrationThe filtrate was concentrated
- custompurified by prep
Sources & evidence
- ORD record
- ord-8899647ae100409b9ed8d63a864996ee
- Source dataset
- uspto-grants-2006_07
- Patent number
- US07081454B2
Reaction notes
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