Formaldehyde → ethyl 5-bromo-8-carbamoyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate

HRID 2361436Notes

Reaction equation

[NH2:1][CH:2]([CH2:8][C:9]1[C:17]2[C:12](=[C:13]([C:19](=[O:21])[NH2:20])[CH:14]=[CH:15][C:16]=2[Br:18])[NH:11][CH:10]=1)[C:3]([O:5][CH2:6][CH3:7])=[O:4].[CH2:22]=O>CO.Cl>[Br:18][C:16]1[CH:15]=[CH:14][C:13]([C:19](=[O:21])[NH2:20])=[C:12]2[C:17]=1[C:9]1[CH2:8][CH:2]([C:3]([O:5][CH2:6][CH3:7])=[O:4])[NH:1][CH2:22][C:10]=1[NH:11]2

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of ethyl 2-amino-3-(4-bromo-7-carbamoyl-1H-indol-3-yl)propanoate (3.45 g, 9.74 mmol) in methanol (68.8 mL) and 1 M aqueous HCl (52.9 mL) was added 37% aqueous formaldehyde (0.790 mL, 9.74 mmol) and the resulting mixture was heated at 80° C. After 1.5 h, additional formaldehyde (0.79 mL) was added and heating was continued. After 3.5 h, additional formaldehyde (0.79 mL) was again added and heating was continued. After 6 h, the mixture was cooled to room temperature, concentrated, and partitioned between a solvent mixture of CHCl3 and iPrOH (3:1) and 1 M NaOH and NaHCO3 (aq). The organic phase was washed with brine, dried and concentrated to afford the crude product as a light brown solid (3.16 g, 89% yield). LCMS (M+H)+ m/z 365.8, 367.8.

Workup

temperatureheating
waitAfter 3.5 h
temperatureheating
waitAfter 6 h
temperaturethe mixture was cooled to room temperature
concentrationconcentrated
custompartitioned between a solvent mixture of CHCl3 and iPrOH (3:1) and 1 M NaOH and NaHCO3 (aq)
washThe organic phase was washed with brine
customdried
concentrationconcentrated

Sources & evidence

ORD record: ord-9f1260dc1d2b4bc884762210f42814f9
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08685969B2

Reaction notes

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