Formaldehyde → 2-(4-(5-Bromopyrimidin-2-ylamino)phenyl)-3-hydroxypropanoic acid

Participants

Reaction Steps

2-(4-(5-Bromopyrimidin-2-ylamino)phenyl)-N-methoxy-N-methylacetamide 23 (2.0 mmol), paraformaldehyde (6.0 mmol) and sodium ethoxide (12.0 mmol) are dissolved in DMSO (10 mL). The reaction mixture is stirred at rt for 1 h. Then a solution of KOH (12.0 mmol) in H2O (5.0 mL) and EtOH (5.0 mL) is added. The reaction mixture is heated at 50° C. for 5 h. After the reaction is completed, the reaction mixture is washed with DCM (50 mL). The aqueous phase is acidified to pH ˜5 and extracted with DCM (2×50 mL). The organic layer is separated, dried and concentrated to yield 2-(4-(5-bromopyrimidin-2-ylamino)phenyl)-3-hydroxypropanoic acid 25, which is used in the next step without further purification. 1H NMR (400 MHz, d6-DMSO) δ 12.30 (bs, 1H), 9.84 (s, 1H), 8.57 (s, 2H), 7.61 (d, J=8.4 Hz, 2H), 7.21 (d, J=8.4 Hz, 2H), 3.90 (t, J=8.8 Hz, 1H), 3.49-3.61 (m, 2H), 3.35 (bs, 1H). MS (m/z) (M+1)+: 338.0, 340.0.

Provenance & Evidence