Water → 1-(2-Acetyl-9-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-7-yl)-4-(benzyloxy)pyridin-2(1H)-one

HRID 1020674Notes

Reaction equation

HRID 1020674 reaction equation
[C:1](Cl)([CH3:3])=[O:2].Cl.Cl.[CH2:7]([O:14][C:15]1[CH:20]=[CH:19][N:18]([C:21]2[CH:29]=[C:28]3[C:24]([C:25]4[CH2:34][CH2:33][NH:32][CH2:31][C:26]=4[N:27]3[CH3:30])=[CH:23][CH:22]=2)[C:17](=[O:35])[CH:16]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.CCN(CC)CC.O>CN(C1C=CN=CC=1)C.C(Cl)Cl>[C:1]([N:32]1[CH2:33][CH2:34][C:25]2[C:24]3[C:28](=[CH:29][C:21]([N:18]4[CH:19]=[CH:20][C:15]([O:14][CH2:7][C:8]5[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=5)=[CH:16][C:17]4=[O:35])=[CH:22][CH:23]=3)[N:27]([CH3:30])[C:26]=2[CH2:31]1)(=[O:2])[CH3:3]

Participants

7

Reactant 4

HCID 962WaterHCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 68658137HCID 68658137, compound

Product 1

HCID 579502611-(2-Acetyl-9-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-7-yl)-4-(benzyloxy)pyridin-2(1H)-oneYield 66.1%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

AcCl (0.023 mL, 0.32 mmol) was added to a solution of 4-(benzyloxy)-1-(9-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-7-yl)pyridin-2(1H)-one dihydrochloride (100 mg, 0.216 mmol), DMAP (5 mg, 0.04 mmol) and Et3N (0.09 mL, 0.6 mmol) in CH2Cl2 (20 mL) under N2, and the resulting solution was stirred at 25° C. for 4 h. H2O was added to the solution, and the phases were separated. The organic phase was washed with saturated NH4Cl solution, dried over Na2SO4 and concentrated under reduced pressure. Flash chromatography (silica gel, (1:1 EtOAc/hexanes)/(9:0.9:0.1 CH2Cl2/MeOH/NH4OH), 100:0 to 0:100) afforded the title compound (61 mg, 66%) as a mixture of rotomers as a white powder: mp 80-82° C.; 1H NMR (500 MHz, DMSO-d6) δ 7.56 (d, J=7.5 Hz, 1H), 7.52-7.35 (m, 7H), 6.94 (dd, J=8.0, 1.5 Hz, 1H), 6.12-6.08 (m, 1H), 5.97 (d, J=3.0 Hz, 1H), 5.15 (s, 2H), 4.77-4.72 (m, 2H), 3.82-3.72 (m, 2H), 3.69-3.65 (m, 3H), 3.82-2.78 (m, 1.3H), 2.71-2.68 (m, 0.7H), 2.16 (s, 3H); ESI MS m/z 428 [M+H]+.

Workup

  1. customthe phases were separated
  2. washThe organic phase was washed with saturated NH4Cl solution
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-d304d9220ecf49f0b24c4baf673f5f4b
Source dataset
uspto-grants-2014_05
Patent number
US08716308B2

Reaction notes

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