反应详情

Oxalyl chloride (1.50 mL, 16.8 mmol) then DMF (2 drops) were added to a mixture of 5-bromopyrimidine-2-carboxylic acid (prepared according to literature procedure described in WO 2005/028452) (2.86 g, 14.0 mmol) in DCM (40 mL). The reaction mixture was stirred at RT for 2 hours, the volatiles removed in vacuo and the residue dissolved in DCM (40 mL). Azetidine hydrochloride (1.44 g, 15.4 mmol) followed by triethylamine (4.29 mL, 30.8 mmol) were added and the mixture stirred at RT for 72 hours. The mixture was concentrated in vacuo and ethyl acetate (100 mL) added to the residue. The organics were washed with water (100 mL), citric acid solution (50 mL), saturated sodium bicarbonate solution (50 mL), brine (50 mL), dried (MgSO4), filtered and the solvent removed in vacuo to give a yellow solid which was chromatographed on silica, eluting with a gradient of 50-100% ethyl acetate in isohexane, to give the desired compound (0.86 g). 1H NMR δ (CDCl3): 2.39 (quin, 2H), 4.32 (t, 2H), 4.63 (t, 2H), 8.92 (s, 2H); m/z 242, 244 (M+H)+

1. customthe volatiles removed in vacuo
2. dissolutionthe residue dissolved in DCM (40 mL)
3. additionwere added
4. stirringthe mixture stirred at RT for 72 hours
5. concentrationThe mixture was concentrated in vacuo and ethyl acetate (100 mL)
6. additionadded to the residue
7. washThe organics were washed with water (100 mL), citric acid solution (50 mL), saturated sodium bicarbonate solution (50 mL), brine (50 mL)
8. dry with materialdried (MgSO4)
9. filtrationfiltered
10. customthe solvent removed in vacuo
11. customto give a yellow solid which
12. customwas chromatographed on silica
13. washeluting with a gradient of 50-100% ethyl acetate in isohexane