Indole → ethyl (10R,15S)-3-oxo-1,4,12-triazatetracyclo[7.6.1.05,16.010,15]hexadeca-5,7,9(16)-triene-12-carboxylate

Participants

Reaction Conditions

Reaction Steps

The procedure described in Example 4, Steps E through G, was utilized to prepare ethyl-2-oxo-2,3,9,10-tetrahydro-1H-pyrido[3′,4′:4,5]-pyrrolo[1,2,3-de]quinoxaline-8(7H)-carboxylate from the corresponding amine, 1,3,4-trihydroquinoxalin-2-one, and ethyl 4-oxopiperidinecarboxylate. This indole (5.74 g, 19.2 mmol) was dissolved in TFA (100 mL). The reaction was cooled to 0° C. NaCNBH3 (3.96 g, 63.0 mmol) was added in small portions over 30 min, keeping the temperature less than 5° C. The reaction was stirred at r.t. for 4 hr. Ice was added to the reaction flask, and the reaction was basified with 50% NaOH until pH=12. Water (80 mL) was added to dissolve the precipitate. The reaction was extracted with CHCl3 (3×200 mL). The combined organic layers were washed with brine, dried, and concentrated to afford ethyl (6bR,10aS)-2-oxo-2,3,6b,9,10,10a-hexahydro-1H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxaline-8(7H)-carboxylate (4.41 g, 77%). 1H NMR (CDCl3, 300 MHz) δ 8.45 (bs, 1H), 6.86 (d, J=7.4 Hz, 1H), 6.74 (dd, J=7.7 Hz, 7.7 Hz, 1H), 6.63 (d, J=7.3 Hz, 1H), 4.15 (q, J=7.0 Hz, 2H), 3.89–3.993 (m, 2H), 3.41–3.47 (m, 2H), 3.33–3.41 (m, 2H), 3.12–3.31 (m, 1H), 2.69–2.75 (m, 2H), 1.90–1.92 (m, 2H), 1.28 (t, J=7.3 Hz, 3H) ppm. MS-APcI: 302 [MH]+

Provenance & Evidence