1-Hydroxybenzotriazole → 7-{4-[3-(tert-Butyldimethylsilanyloxy)propyl]thiazol-2-yl}-6-[cyclopropyl-(2,3-dichlorobenzyl)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 D2 (2.87 g, 4.60 mmol), cyclopropyl-(2,3-dichlorobenzyl)amine (prepared from 2,3-dichlorobenzaldehyde and cyclopropylamine by reductive amination, 2.49 g, 11.5 mmol), DIPEA (3.15 mL, 18.4 mmol), DMAP (140 mg, 1.15 mmol), HOBt (932 mg, 6.90 mmol) and EDC.HCl (2.65 g, 13.8 mmol) in CH2Cl2 (50 mL) was stirred at rt for 6 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 (1.30 g, 34%). LC-MS: tR=1.33 min, ES+: 821.54.

Provenance & Evidence