Tert-butyl 3-oxopyrrolidine-1-carboxylate → 3-((R)-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-pyrrolidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Steps

A solution of (R)-6-amino-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (Example #148, Step D, 2.4 g, 10.32 mmol) and tert-butyl 3-oxopyrrolidine-1-carboxylate (Aldrich, 2.0 g, 6.23 mmol) was stirred at 15° C. for 10 min and then acetic acid (7 mL) was added. The reaction mixture was stirred for 30 min and sodium cyanoborohydride (0.68 g, 11 mmol) was added. The reaction mixture was stirred at ambient temperature overnight then concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluting with 100% EtOAc) to give 3-((R)-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-pyrrolidine-1-carboxylic acid tert-butyl ester (2.3 g, 53%) as a yellow solid. 1H-NMR (400 MHz, DMSO-d6): δ 10.71 (s, 1H), 6.75 (d, J=8.4 Hz, 1H), 6.42 (s, 1H), 6.20 (d, J=8.4 Hz, 1H), 5.63-5.53 (m, 1H), 4.73 (m, 1H), 4.52-4.41 (m, 2H), 4.06-3.99 (m, 1H), 3.62-3.37 (m, 2H), 3.15-2.92 (m, 1H), 2.10 (m, 1H), 1.64 (m, 1H), 1.38 (s, 9H), 1.30 (m, 3H). LCMS (Table 1, Method 2) Rt=1.059 min.; MS m/z: 424 [M+Na]+.

Provenance & Evidence