1-Hydroxybenzotriazole → 7-{5-[2-(tert-Butyldimethylsilanyloxy)ethyl]-4-methylthiazol-2-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

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Reaction Steps

A mixture of compound D1 (10.52 g, 13.6 mmol), cyclopropyl-(3-methoxy-2-methylbenzyl)amine (prepared by reductive amination from 3-methoxy-2-methylbenzaldehyde, Comins, D. L.; Brown, J. D., J. Org. Chem., 1989, 54, 3730 and cyclopropylamine, 6.54 g, 34.2 mmol), DIPEA (9.40 mL, 54.9 mmol), DMAP (417 mg, 3.40 mmol), HOBt (2.77 g, 20.5 mmol) and EDC.HCl (7.84 g, 40.9 mmol) in CH2Cl2 (150 mL) was stirred at rt for 3 days. The mixture was diluted with more CH2Cl2, and washed with aq. 1M HCl (3×) and aq. sat. NaHCO3 (1×). The org. extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (EtOAc/heptane 1:5→1:3→1:2→1:1→3:2) yielded the title compound (7.93 g, 70%). LC-MS: tR=1.30 min, ES+: 797.67.

Provenance & Evidence