1,8-Diazabicyclo(5.4.0)undec-7-ene → benzyl trans-3-fluoro-4-{[6-methyl-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinazolin-4-yl]amino}pyrrolidine-1-carboxylate

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Reaction Steps

A suspension of 6-methyl-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4 (5H)-yl)quinazolin-4(3H)-one (600 mg, 1.77 mmol, prepared in analogy to the one in Example 91), benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (1.02 g, 2.3 mmol), and 1,8-diazabicyclo[5.4.0]undec-7-ene (400 mg, 2.6 mmol) in anhydrous N,N-dimethylformamide (10 mL) was stirred at room temperature for 10 minutes. Then a solution of benzyl trans-3-amino-4-fluoropyrrolidine-1-carboxylate (500 mg, 2.1 mmol) in N,N-dimethylformamide (5 mL) was added dropwise. After being heated at 60° C. overnight, the mixture was diluted with water (50 mL), extracted with dichloromethane (50 mL). The organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was purified by flash column chromatography (gradient eluting with 10% to 25% ethyl acetate in dichloromethane) to afford 415 mg of the desired product as a yellow solid (yield was 41.8%).

Provenance & Evidence