1-Hydroxybenzotriazole → 7{2-[3-(tert-Butyldimethylsilanyloxy)propyl]thiazol-5-yl}-6-[cyclopropyl-(3-methoxy-2-methylbenzyl)carbamoyl]-3,9-diazabicyclo[3.3.1]non-6-ene-3,9-dicarboxylic acid di-tert-butyl ester

Participants

Reaction Steps

To a stirred sol. of compound D6 (2.66 g, 4.26 mmol) in CH2Cl2 (45 mL) were added EDC.HCl (2.04 g, 10.6 mmol), HOBt (783 mg, 5.11 mmol), DMAP (13 mg, 0.107 mmol), and DIPEA (3.35 mL, 19.19 mmol). After 15 min cyclopropyl-(3-methoxy-2-methyl-benzyl)amine (prepared by reductive amination from 3-methoxy-2-methylbenzaldehyde, Comins, D. L.; Brown, J. D., J. Org. Chem., 1989, 54, 3730 and cyclopropylamine, 2.45 g, 12.80 mmol) was added and stirring was continued over 6 days. Three times were added cyclopropyl-(3-methoxy-2-methyl-benzyl)amine (817 mg, 4.27 mmol) and HOBt (392 mg, 2.55 mmol). The reaction mixture was partitioned between aq. 1M HCl and CH2Cl2, and the phases were separated. The org. layer was washed with aq. sat. NaHCO3, dried over MgSO4, filtered, and the solvents were removed in vacuo. Purification by FC (heptane/EtOAc 7/3→1/1) yielded the title product (1.91 g, 56%). LC-MS: tR=1.27 min, ES+: 797.59.

Provenance & Evidence