反应详情

Under an atmosphere of argon protective gas, N-Boc-Gly-OH (5 mg, 28 μmol) and NMM (5.3 mg, 52 μmol, 2.4 eq.) were dissolved in abs. THF (1 ml), and isobutyl chloroformate (4.2 mg, 31 μmol, 1.4 eq.) was added at −15° C. (solution A). At −78° C., (7R)-2-amino-7-(4-cyanophenyl)-5-methyl-4-[3-(trifluoromethyl)phenyl]-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidine-6-carbonitrile hydrochloride (10 mg, 22 μmol) and NMM (2.2 mg, 22 μmol, 1 eq.) were added, and the mixture was stirred overnight, during which time it slowly warmed to RT. Since the conversion was still incomplete, more solution A consisting of in each case 285 μmol of N-Boc-Gly-OH, isobutyl chloroformate and NMM in abs. THF was added at −15° C., and the mixture was stirred for 3 d, warming to RT. The reaction mixture was then directly purified by preparative HPLC (Gromsil C18 column, 30×250 mm; mobile phase: acetonitrile-water-0.1% TFA). After lyophilization, the product was obtained as a solid (6.3 mg, 50% of theory).

1. stirringthe mixture was stirred for 3 d
2. temperaturewarming to RT
3. customThe reaction mixture was then directly purified by preparative HPLC (Gromsil C18 column, 30×250 mm; mobile phase: acetonitrile-water-0.1% TFA)
4. customAfter lyophilization, the product was obtained as a solid (6.3 mg, 50% of theory)