Ammonia methanol → 2-bromo-7-(morpholine-4-carbonyl)-5H-pyrido[3,2-b]indole-4-carboxamide
Reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:23](OC)=[O:24])[C:5]2[NH:6][C:7]3[CH:8]=[C:9]([C:15]([N:17]4[CH2:22][CH2:21][O:20][CH2:19][CH2:18]4)=[O:16])[CH:10]=[CH:11][C:12]=3[C:13]=2[N:14]=1.[NH3:27].CO>>[Br:1][C:2]1[CH:3]=[C:4]([C:23]([NH2:27])=[O:24])[C:5]2[NH:6][C:7]3[CH:8]=[C:9]([C:15]([N:17]4[CH2:18][CH2:19][O:20][CH2:21][CH2:22]4)=[O:16])[CH:10]=[CH:11][C:12]=3[C:13]=2[N:14]=1Participants
Conditions
- Temperature
- 105 °C
Procedure
Methyl 2-bromo-7-(morpholine-4-carbonyl)-5H-pyrido[3,2-b]indole-4-carboxylate (1.008 g, 2.410 mmol, Example 212D) was suspended in NH3/MeOH (7M) (18 mL, 126 mmol) in a sealed microwave vial. The mixture was heated at 105° C. for 8 hours in a microwave reactor. Product crystallized from reaction mixture upon cooling and was collected by filtration, washed with MeOH and dried in nitrogen stream to give 736.4 mg 2-bromo-7-(morpholine-4-carbonyl)-5H-pyrido[3,2-b]indole-4-carboxamide. 1H NMR (DMSO-d6) δ ppm 11.4 (b, 1H), 8.56 (s, 1H), 8.22 (d, 1H, J=8.6), 7.81 (s, 1H), 7.31 (dd, 1H, J=7.9, 1.2), 3.75-3.35 (b, 10H). MS (ESI) m/e−=401/403, m/e+=403/405 (1 Br isotope pattern) consistent with [M−H]− and [M+H]+. HPLC retention time 6.74 min. (Sunfire C18 3.5 μm, 4.6×150 mm column, 15 min gradient, 10-100% B, 1 mL/min. Solvent A: 5% CH3CN—95% H2O—0.1% TFA; Solvent B: 95% CH3CN—5% H2O—0.1% TFA).
Workup
- customProduct crystallized from reaction mixture
- temperatureupon cooling
- filtrationwas collected by filtration
- washwashed with MeOH
- customdried in nitrogen stream
Sources & evidence
- ORD record
- ord-a3db3cdc4347434bb837282cf09d39e9
- Source dataset
- uspto-grants-2014_08
- Patent number
- US08815840B2
Reaction notes
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