Diisopropylethylamine → (R,E)-6-amino-9-(1-(4-(cyclopropyl(methyl)amino)but-2-enoyl)pyrrolidin-3-yl)-7-(4-phenoxyphenyl)-7H-purin-8(9H)-one

Participants

Reaction Steps

A solution of (R)-6-amino-7-(4-phenoxyphenyl)-9-(pyrrolidin-3-yl)-7H-purin-8(9H)-one (62) (95 mg, 0.24 mmol), 4-(cyclopropyl(methyl)amino)but-2-enoic acid hydrochloride (69 mg, 0.36 mmol) and DIPEA (213 μL, 1.2 mmol) in 5 mL dry DMF was cooled to 0° C. HBTU (190 mg, 0.49 mmol) was added in one portion. The reaction mixture was allowed to warm to rt, and stirred for 2 hrs under N2, then purified directly by Gilson using 10 to 95% acetonitrile in water (0.2% NH3.H2O) to give (R,E)-6-amino-9-(1-(4-(cyclopropyl(methyl)amino)but-2-enoyl)pyrrolidin-3-yl)-7-(4-phenoxyphenyl)-7H-purin-8(9H)-one (63) (31 mg, 17.7%) as a light yellow solid. LC-MS (ESI): m/z (M+1) 526. 1H NMR (400 MHz, DMSO) δ 8.14 (d, J=6.0 Hz, 1H), 7.55-7.34 (m, 4H), 7.30-7.08 (m, 5H), 6.76-6.59 (m, 1H), 6.36 (dd, J=37.4, 15.1 Hz, 1H), 5.82 (d, J=9.1 Hz, 2H), 5.20-4.99 (m, 1H), 4.11-3.40 (m, 4H), 3.26 (dd, J=17.7, 6.4 Hz, 2H), 2.78-2.59 (m, 1H), 2.24 (d, J=12.4 Hz, 3H), 1.80-1.63 (m, 1H), 0.51-0.37 (m, 2H), 0.37-0.24 (m, 2H).

Provenance & Evidence