Sodium Thiosulfate → methyl (3R,4S)-3-[(3,6-diethyl-5-iodopyrazin-2-yl)amino]-4-ethoxypyrrolidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of the methyl (3R,4S)-3-[(3,6-diethylpyrazin-2-yl)amino]-4-ethoxypyrrolidine-1-carboxylate (5.25 g, 16.2 mmole) in DMF (0.3M, 54 ml) under N2 was added N-iodosuccinimide (4.57, 1.25 eq.). The reaction mixture was heated at 50° C. for 2 hours then cooled to ambient temperature. It was poured into saturated sodium thiosulfate (100 mL) and extracted with ethyl acetate (2×100 ml), dried with MgSO4, filtered and concentrated. Purification with Biotage MPLC (40 g, 10-30% ethyl acetate in heptane gradient) provided 6.45 g (89%) of methyl (3R,4S)-3-[(3,6-diethyl-5-iodopyrazin-2-yl)amino]-4-ethoxypyrrolidine-1-carboxylate as a white solid. 1H NMR (400 MHz, CDCl3) δ 5.06 (m, 1 H), 4.62 (m, 1 H), 4.05 (m, 1 H), 3.88 (m, 1 H), 3.73 (m, 5 H), 3.58 (m, 1 H), 3.43 (m, 1 H), 3.18 (m, 1 H), 2.80 (m, 2 H), 2.62 (q, J=15.8 Hz, 2 H), 1.26 (m, 9 H); IR (diffuse reflectance) 3432, 2976, 2969, 2498, 2461, 2388, 2350, 2337, 1697, 1550, 1535, 1457, 1451, 1392, 771 (s) cm−1 HRMS (ESI) calcd for C16H25N4O3I+H1 449.1051. found 449.1029. Anal. Calcd for C16 H25 I N4 O3: C, 42.87; H, 5.62; N, 12.50. Found: C, 43.01; H, 5.73; N, 12.43.

Provenance & Evidence