Acetic Acid → 2-(S)-{[2-Chloro-4-(4-methoxy-phenoxy)-pyrimidin-5-ylamino]-methyl}-pyrrolidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Steps

To a solution of Compound 1c (4.45 g, 17.7 mmol) in 1,2-dichloroethane (80 mL) was added Boc-L-prolinal (Compound 1d) (5.0 g; 24.4 mmol) and glacial acetic acid (4.5 mL) at ambient temperature, and the mixture was stirred under a nitrogen atmosphere for 3 h. The mixture was then treated with NaB(OAc)3H (9.37 g; 44.2 mmol) and continually stirred at room temperature for 20 h. The resultant mixture was diluted with CH2Cl2, and washed with saturated NaHCO3 (aq) and H2O. The organic phase was washed sequentially with H2O and brine, and then dried over Na2SO4. The mixture was filtered and the filtrate was evaporated under reduced pressure to give the crude material. The crude material was purified by flash column chromatography (SiO2), eluting with a Et2O—CH2Cl2 gradient to afford Compound 1e (6.54 g; 85% yield) as a pale-yellow solid. 1H-NMR (400 MHz, CDCl3): δ 7.73-7.79 (m, 1H), 7.07-7.14 (m, 2H), 6.91-6.98 (m, 2H), 5.73 (br. s, 0.6H), 4.77 (br. s, 0.4H), 4.20-4.30 (m, 1H), 3.85 (s, 3H), 3.21-3.58 (m, 4H), 1.81-2.11 (m, 4H), 1.46-1.49 (m, 9H); MS: m/z 435.1 (M+H)+.

Provenance & Evidence