Iodoacetamide → tert-butyl 6-(2-amino-2-oxoethyl)-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate

Preparation of tert-butyl 6-(2-amino-2-oxoethyl)-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate tert-Butyl 1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate (0.0994 g, 0.347) and iodoacetamide (0.0704 g, 0.381 mmol, 1.10 equiv.) was dissolved in DMF (1 mL) at rt under N2. NaH (0.033 g, 0.825 mmol, 2.38 equiv., 60% dispersion) was added, and the reaction mixture was stirred for 16 h. Additional NaH (0.039 g) was added and the reaction mixture was stirred for 1.5 h. The reaction mixture was poured over ice, and the resulting mixture was extracted with EtOAc. The organic extracts was washed with water and then with brine. The organic extracts was dried over MgSO4, filtered, and concentrated. The crude product (0.124 g) was purified by PTLC (2×1 mm×20 cm×20 cm SiO2 plates, developed with 3:1 EtOAc:hexane, eluted with 10% MeOH in CH2Cl2) to give tert-butyl 6-(2-amino-2-oxoethyl)-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate (0.0233 g) in 19% yield. 1H NMR (300 MHz, CDCl3) δ 1.50, 2.93-3.07, 3.68-3.79, 4.71, 5.33, 5.90-5.94, 7.15-7.24, 7.50-7.54; MS (ESI+) for C19H25N3O3 m/z 344.1 (M+H)+.

1. stirringthe reaction mixture was stirred for 1.5 h
2. additionThe reaction mixture was poured over ice
3. extractionthe resulting mixture was extracted with EtOAc
4. washThe organic extracts was washed with water
5. dry with materialThe organic extracts was dried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated
8. customThe crude product (0.124 g) was purified by PTLC (2×1 mm×20 cm×20 cm SiO2 plates, developed with 3:1 EtOAc:hexane, eluted with 10% MeOH in CH2Cl2)

ORD record

ord-d814741b5ea3404aa99e2331dd83e1d5

Source dataset

uspto-grants-2004_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06828314B2