1,2-Dichloroethane → GDC-0349

Participants

Reaction Conditions

Reaction Steps

A mixture of (S)-1-ethyl-3-(4-(4-(3-methylmorpholino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea (ca) (1.0 g, 2.5 mmol), 3-oxetanone (0.91 mL, 13 mmol) and sodium triacetoxyborohydride (1.7 g, 8.1 mmol) in 1,2-dichloroethane (25 mL, 320 mmol) was stirred at 70° C. under N2 for 3 h. The mixture was then cooled down and poured in diluted NaHCO3. The organic and aqueous phases were separated. The aqueous phase was extracted with 2×50 mL of DCM. The combined organic phases were dried with Magnesium sulfate, filtered and concentrated. The crude solid was purified by flash chromatography (100% DCM to 5% MeOH/DCM) to provide product ih as a pale yellow solid: 1H NMR (400 MHz, DMSO) δ 8.61 (s, 1H), 8.15 (d, J=8.7 Hz, 2H), 7.46 (d, J=8.7 Hz, 2H), 6.15 (s, 1H), 4.64 (t, J=6.5 Hz, 2H), 4.55 (d, J=5.9 Hz, 2H), 4.13 (d, J=6.7 Hz, 1H), 3.87 (d, J=11.4 Hz, 1H), 3.62 (dd, J=34.1, 22.2 Hz, 6H), 3.43 (d, J=16.1 Hz, 2H), 3.20-3.04 (m, 2H), 2.69 (d, J=4.6 Hz, 3H), 1.24 (d, J=6.6 Hz, 3H), 1.06 (t, J=7.2 Hz, 3H); LC-MS: m/z=+453 (M+H)+.

Provenance & Evidence