Acetic Acid → 4-{4-(4-Fluorophenyl)-1-[1-(pyrimidin-2-ylmethyl)azetidin-3-yl]-1H-imidazol-5-yl}pyrimidin-2-amine

Participants

Reaction Steps

A mixture of 4-[1-azetidin-3-yl-4-(4-fluorophenyl)-1H-imidazol-5-yl]pyrimidin-2-amine (C5) (11.2 mg, 0.0361 mmol), pyrimidine-2-carbaldehyde (5.9 mg, 0.055 mmol), triethylamine (0.010 mL, 0.072 mmol) and acetic acid (0.010 mL, 0.17 mmol) in 1,2-dichloroethane (1.0 mL) was stirred for 30 minutes. Sodium triacetoxyborohydride (22.9 mg, 0.11 mmol) was added and stirring was continued for an additional 18 hours, at which time the reaction was quenched with dilute aqueous sodium hydroxide solution. Extraction of the aqueous layer with 1,2-dichloroethane was followed by combination of the organic layers and concentration in vacuo. Purification of the residue was effected by reversed-phase HPLC (Gradient: 5% to 60% acetonitrile in water) to provide the product as a yellow oil. Yield: 1 mg, 0.0025 mmol, 7%. LCMS m/z 403.6 (M+1). 1H NMR (400 MHz, CD3OD) δ 3.66-3.70 (m, 2H), 3.96-4.00 (m, 2H), 4.02 (s, 2H), 5.34 (m, 1H), 6.38 (d, J=5.2 Hz, 1H), 7.10 (dd, J=8.8, 8.8 Hz, 2H), 7.38 (t, J=4.9 Hz, 1H), 7.44 (dd, J=8.9, 5.4 Hz, 2H), 8.09 (d, J=5.2 Hz, 1H), 8.24 (br s, 1H), 8.77 (d, J=5.0 Hz, 2H).

Provenance & Evidence