反应详情

A solution of N-acetyl-D-thioproline-L-tyrosine methyl ester (1.76 g, 5 mmol), [prepared from N-acetyl-D-thioproline and tyrosine methyl ester by a similar method to the preparation of Intermediate 5] in DMF (10 ml) was added to a suspension of sodium hydride (60% in mineral oil, 210 mg, 5.25 mmol) in DMF (5 ml) at room temperature. After 10 min a solution of 2,4-dichloropyrimidine (782 mg, 5.25 mmol) in DMF (5 ml) was added. After 1 h water (1 ml) was added and the solvent evaporated in vacuo. The residue was dissolved in EtOAc (200 ml) and washed with water (3×50 ml) and brine (30 ml), dried (Na2SO4) and evaporated in vacuo. Chromatography (SiO2, MeOH/DCM 5:95) gave the title compound as a white foam (1.59 g, 68%). δH (DMSO-d6, 400K) 8.56 (1 H, d, J 5.7 Hz, PyrH), 7.9 (1 H, br d, CONH),7.32 (2 H, d,J 8.7 Hz, ArH), 7.15 (2 H, d, J 8.7 Hz, ArH), 6.99 (1 H, d, J 5.7 Hz, PyrH), 4.83 (1 H, dd, J 7.4, 3.9 Hz, CHαthiopro), 4.77 (1 H, d, J 9.2 Hz, NCHHBS), 4.64 (1 H,dt, J 8.5, 5.6 Hz, CHαtyr),4.39 (1 H, d, J 9.2 Hz, NCHAHBS), 3.67 (3 H, s, CO2Me), 3.26 (1 H, dd, J 11.6, 7.4 Hz, CHCHAHBS), 3.19 (1 H, dd, J 14.0, 5.7 Hz, CHCHAHBAr), 3.09-3.00 (2 H, m, CHCHAHBS+CHCHAHBAr) and 2.00 (3 H, s,COCH3); m/z (ESI, 15 V) 465 (MH+).

1. customthe solvent evaporated in vacuo
2. dissolutionThe residue was dissolved in EtOAc (200 ml)
3. washwashed with water (3×50 ml) and brine (30 ml)
4. dry with materialdried (Na2SO4)
5. customevaporated in vacuo