4-Methylmorpholine → HCID 86708118, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 4-(tert-butoxycarbonyl-methyl-amino)-butyric acid (109 mg, 0.50 mmol) in THF (5 mL) was treated with 4-methyl-morpholine (101 mg, 1.0 mmol) followed by isobutyl chloroformate (68 mg, 0.5 mmol) and cooled to −22° C. under argon. The reaction mixture was stirred for 20 mins while warming to −15° C. After re-cooling to −24° C., 4-{5-[2-amino-7-methyl-8-(3-trifluoromethyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl]-pyrazol-1-yl}-benzonitrile (Ex. 1, 230 mg, 0.50 mmol) was added and the resulting suspension was slowly warmed to RT and stirred for 16 hrs. The reaction mixture was treated with a fresh batch of 1-({[(4-{[(tert-butoxy)carbonyl] (methyl)-amino}butanoyl)oxy]carbonyl}oxy)-2-methylpropane prepared from a solution of 4-(tert-butoxycarbonyl-methyl-amino)-butyric acid (218 mg, 1.0 mmol) in THF (5 mL), 4-methyl-morpholine (101 mg, 1.0 mmol) and isobutyl chloroformate (137 mg, 1.0 mmol) at RT. The reaction mixture was stirred at RT for 24 hrs and then heated at 60° C. for 7 hrs. After standing at RT for 18 hrs, the volatiles were removed in vacuo and the resulting residue was purified by flash chromatography eluting with a gradient of 0-100% EtOAc in DCM. The product containing fractions were concentrated in vacuo and the resulting residue (456 mg, 0.5 mmol) in THF (5 mL) was treated with a fresh batch of 1-({[(4-{[(tert-butoxy)carbonyl] (methyl)amino}butanoyl)oxy]carbonyl}oxy)-2-methylpropane prepared from a solution of 4-(tert-butoxycarbonyl-methyl-amino)-butyric acid (1.09 g, 5.0 mmol) in THF (20 mL), 4-methyl-morpholine (760 mg, 7.55 mmol) and isobutyl chloroformate (680 mg, 5.01 mmol) at RT. The resulting mixture was heated at 50° C. for 65 hrs and then purified by flash chromatography eluting with a gradient of 0-100% EtOAc in DCM followed by 10% MeOH in DCM affording the title compound (241 mg).

Provenance & Evidence