4-tert-Butylbenzoyl chloride → 4-tert-butyl-N-{7-methoxy-3-[2-(methylamino)pyrimidin-4-yl]-1-naphthyl}benzamide

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Reaction Steps

A mixture of 4-(4-amino-6-methoxy-2-naphthyl)-N-methylpyrimidin-2-amine (33) (252 mg, 0.900 mmol), N,N-dimethylacetamide (4 mL) was treated with N,N-diisopropylethylamine (0.9 mL, 5.2 mmol) followed by 4-(tert-butyl)benzoyl chloride (181 mg, 0.9 mmol) and stirred for 16 hours at room temperature. The mixture was partitioned between ethyl acetate (150 mL) and water (120 mL). The aqueous layer was removed and the organic layer was washed with water (2×100 mL), dried over anhydrous sodium sulfate, filtered, concentrated (rotary) and dried under high vacuum to afford the crude desired product, which was purified by reverse phase chromatography on preparative LC/UV/MS system using a mass triggered fractionation. Compound was eluted from the HPLC column (Maccel 120-10-C18 SH 10 μm 20 mmID×50 mm) at 88 mL/min with acetonitrile/water gradient using 0.1% FA as a modifier. 4-tert-butyl-N-{7-methoxy-3-[2-(methylamino)pyrimidin-4-yl]-1-naphthyl}benzamide (184) was isolated as an off-white solid (95 mg). M.p.=231-232° C.; 400 MHz 1H NMR (DMSO-d6) δ: 10.39 (s, 1H), 8.59 (s, 1H), 8.34-8.39 (m, 2H), 8.06 (m, 3H), 7.61 (d, J=6.7 Hz, 2H), 7.31 (m, 3H), 7.16 (s, 1H), 3.87 (s, 3H), 3.34 (br s, 3H), 1.36 (s, 9H); Experimental Elemental Analysis (0.23 equivalents of formic acid)=72.52% C, 6.15% H, 12.21% N; Calculated Elemental Analysis 72.50% C, 6.36% H, 12.42% N; LCMS (m/z): 442 [M+H].

Provenance & Evidence