反应详情

A solution of 5-[(3-{[(1S)-1-(hydroxymethyl)propyl]oxy}-5-{[(1-methyl-1H-pyrazol-3-yl)amino]carbonyl}phenyl)oxy]pyrazine-2-carboxylic acid (12 mg, 0.03 mmol), azetidine hydrochloride (4 mg, 0.06 mmol), HATU (14 mg, 0.04 mmol) and DIPEA (0.02 mL, 0.11 mmol) in DMF (1 mL) was stirred at RT over the weekend. Water (15 mL) was added and the solution extracted with ethyl acetate (25 mL). The ethyl acetate layer was washed with brine (20 mL), dried (MgSO4), and evaporated to a residue which was chromatographed by preparative HPLC on C18 reversed phase, eluting with 5-95% acetonitrile (+0.2% TFA) in water (+0.2% TFA), to give the required product along with 15% of a co-eluting impurity (5 mg). 1H NMR δ (CDCl3): 0.92 (t, 3H), 0.97 (t, 0.45H), 1.69 (quin, 2H), 1.76 (m, 0.3H), 2.34 (quin, 2H), 3.76 (m, 2H), 3.86 (s, 3H), 4.23 (t, 2H), 4.49 (sextet, 1H), 4.66 (t, 2H), 4.77 (m, 0.15H), 6.93 (t, 1H), 6.99 (d, 1H), 7.34 (s, 1H), 7.46 (s, 1H), 7.50 (s, 1H), 8.29 (s, 1H), 8.78 (s, 1H), 10.68 (s, 1H), 10.78 (s, 0.15H); m/z 468 (M+H)+

1. extractionthe solution extracted with ethyl acetate (25 mL)
2. washThe ethyl acetate layer was washed with brine (20 mL)
3. dry with materialdried (MgSO4)
4. customevaporated to a residue which
5. customwas chromatographed by preparative HPLC on C18 reversed phase
6. washeluting with 5-95% acetonitrile (+0.2% TFA) in water (+0.2% TFA)