Formaldehyde → 1-(2-(2-(5-Chloro-2-((4-(1-methylpiperidin-4-yl)phenyl)amino)pyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide

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Reaction Steps

Formaldehyde (37 wt % in H2O; 14 μL, 0.19 mmol) was added to a solution of 1-(2-(2-(5-chloro-2-((4-(piperidin-4-yl)phenyl)amino)pyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide (7) (30 mg, 63 μmol) in MeOH (5.0 mL) under an atmosphere of nitrogen. The resulting mixture was stirred for 10 minutes at room temperature before the addition of sodium triacetoxyborohydride (53 mg, 0.25 mmol). Stirring was continued for 2.5 hours at room temperature before the volatiles were removed in vacuo and the resulting residue was partitioned between EtOAc (20 mL) and saturated aqueous NaHCO3 (20 mL). The layers were separated and the aqueous layer was extracted with EtOAc (2×20 mL). The combined organic layers were washed with brine (20 mL), dried over MgSO4 and the volatiles evaporated in vacuo. The residue was dissolved in acetone (0.5 mL) and petroleum benzine 40-60° C. (25 mL) was added. The resulting green precipitate was isolated by filtration and dried under high vacuum to give the title compound 8 as a green solid (8 mg, 26%); 1H NMR (400 MHz, CDCl3) δ 8.18 (s, 1H), 7.41 (d, J=8.5 Hz, 2H), 7.34 (d, J=7.3 Hz, 1H), 7.30-7.23 (m, 3H), 7.12 (d, J=8.5 Hz, 2H), 5.55 (s, 1H), 5.25 (s, 1H), 3.13 (J m, 6H), 2.52-2.41 (m, 1H), 2.38 (s, 3H), 2.23 (t, J=11.8 Hz, 2H), 1.89 (dd, J=25.4, 12.3 Hz, 2H), 1.80 (d, J=12.3 Hz, 2H), 1.68 (s, 2H), 1.06 (s, 2H). LCMS-A: rt 4.611 min; m/z 491 [M+H]+.

Provenance & Evidence