tert-Butanol → HCID 67271357, compound

Participants

Reaction Steps

Using general method E, the material from the previous reaction (1.26 g, 4.70 mmol) was saponified to yield 2-t-butyl-4-phenylpyrimidine-5-carboxylic acid (1.10 g, 92% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 1.40 (s, 9H), 7.50-7.52 (m, 3H), 7.67-7.69 (m, 2H), 9.02 (s, 1H). 2-t-butyl-4-phenylpyrimidine-5-carboxylic acid (1.10 g, 4.29 mmol) was combined in t-BuOH (11 mL) with DPPA (1.18 g, 4.29 mmol) and Et3N (0.434 g, 4.29 mmol). The mixture was heated at reflux, stirred overnight, then cooled to RT and diluted with EtOAc (75 mL) and H2O (75 mL). The organic phase was separated, washed with brine, dried (Na2SO4) and concentrated. The resultant solid was treated with EtOAc (5 mL) and sonicated for 5 min then filtered free of solids and evaporated to a small volume and the solution purified by column chromatography to yield t-butyl 2-t-butyl-4-phenylpyrimidin-5-ylcarbamate (1.2 g, 85% yield) as a white foam. LC-MS (EI) m/z: 328.3 (M+H+). This material (1.02 g, 3.0 mmol) was dissolved in CH2Cl2 (10 mL) and treated with 3N HCl/EtOAc (10 mL), stirred at RT and subsequently treated with additional 3N HCl/EtOAc (5 mL) and then concentrated to yield 2-t-butyl-4-phenylpyrimidin-5-amine hydrochloride as a yellow solid (0.724 g, 88%). LC-MS (EI) m/z: 228.2 (M+H+). Using general method A, this material (120 mg, 0.455 mmol) and 1,2-dichloro-3-isocyanatobenzene (94 mg, 0.500 mmol) were combined to yield 1-(2-t-butyl-4-phenylpyrimidin-5-yl)-3-(2,3-dichlorophenyl)urea (45 mg, 24% yield). 1H NMR (400 MHz, DMSO-d6): δ 1.39 (s, 9H), 7.29-7.34 (m, 2H), 7.53-7.59 (m, 3H), 7.77-7.79 (m, 2H), 8.06-8.08 (m, 1H), 8.20 (s, 1H), 8.98-9.02 (m, 2H); LC-MS (EI) m/z: 417.0 (M+H+).

Provenance & Evidence