Sodium Carbonate → HCID 66550743, compound

Participants

Reaction Steps

A mixture of (S)-5-chloro-N-(3-(2-methylpyrrolidin-1-yl)phenyl)thiazolo[5,4-d]pyrimidin-7-amine (200 mg, 0.58 mmol), 6-methoxypyridin-3-ylboronic acid (134 mg, 0.87 mmol), Pd2(dba)3 (34 mg, 0.058 mmol), X-Phos (0.58 mg, 0.12 mmol) and sodium carbonate (185 mg, 1.74 mmol) in 1,4-dioxane:water (5 mL:5 mL) was heated to reflux for 16 hours. Then water was added, mixture extracted with ethyl acetate, organics combined washed with brine dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo. The crude product was purified by preparative HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 ml/inj, flow rate: 20 ml/min; wavelength: 214 nm and 254 nm; the gradient conditions are: 20% acetonitrile/80% water (0.1% TFA V/V) initially, and then proceed to 45% acetonitrile/55% water (0.1% TFA V/V) in a linear fashion after just 9 min.) to give (S)-5-(6-methoxypyridin-3-yl)-N-(3-(2-methylpyrrolidin-1-yl)phenyl)thiazolo[5,4-d]pyrimidin-7-amine (60 mg, 24.8%) as yellow solid. 1H NMR (300 MHz, CD3OD): δ 9.19 (s, 1H), 9.08 (s, 1H), 8.63 (dd, 1H, J1=8.7 Hz, J2=2.4 Hz), 7.33 (s, 1H), 7.23-7.12 (m, 2H), 6.88 (d, 1H, J=8.7 Hz), 6.42 (d, 1H, J=6.9 Hz), 3.96 (s, 3H), 3.51-3.46 (m, 1H), 3.30-3.24 (m, 2H), 2.17-2.03 (m, 3H), 1.80-1.75 (m, 1H), 1.22 (d, 3H, J=6.3 Hz). LC-MS: 419 [M+H]+, tR=2.04 min. HPLC: 100% at 214 nm, 100% at 254 nm, tR=6.299 min.

Provenance & Evidence