Water → HCID 49869778, compound

HRID 474936Notes

Reaction equation

HRID 474936 reaction equation
[C:1](Cl)([CH3:3])=[O:2].Cl.[F:6][C:7]1[CH:8]=[CH:9][C:10]([CH2:13][O:14][C:15]2[CH:20]=[CH:19][N:18]([C:21]3[CH:22]=[CH:23][C:24]4[C:25]5[CH2:35][CH2:34][NH:33][CH2:32][CH2:31][C:26]=5[N:27]([CH3:30])[C:28]=4[CH:29]=3)[C:17](=[O:36])[CH:16]=2)=[N:11][CH:12]=1.CCN(CC)CC.O>CN(C1C=CN=CC=1)C.C(Cl)Cl>[C:1]([N:33]1[CH2:34][CH2:35][C:25]2[C:24]3[CH:23]=[CH:22][C:21]([N:18]4[CH:19]=[CH:20][C:15]([O:14][CH2:13][C:10]5[CH:9]=[CH:8][C:7]([F:6])=[CH:12][N:11]=5)=[CH:16][C:17]4=[O:36])=[CH:29][C:28]=3[N:27]([CH3:30])[C:26]=2[CH2:31][CH2:32]1)(=[O:2])[CH3:3]

Participants

7

Reactant 4

HCID 962WaterHCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 66874548HCID 66874548, compound

Product 1

HCID 49869778HCID 49869778, compoundYield 78%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

AcCl (0.01 mL, 0.2 mmol) was added to a solution of 4-((5-fluoropyridin-2-yl)methoxy)-1-(6-methyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indol-8-yl)pyridin-2(1H)-one hydrochloride (49 mg, 0.11 mmol), DMAP (3 mg, 0.03 mmol), and Et3N (0.03 mL, 0.3 mmol) in CH2Cl2 (10 mL) under N2, and the resulting solution was stirred at 25° C. for 4 h. H2O was added and the resulting phases were separated. The organic phase was dried over Na2SO4 and concentrated under reduced pressure. Flash chromatography on silica gel ((1:1 EtOAc/hexanes)/(9:0.9:0.1 CH2Cl2/MeOH/NH4OH), 100:0 to 0:100) afforded 39 mg (78%) of the title compound as a white solid as a mixture of rotomers: mp 88-94° C.; 1H NMR (500 MHz, DMSO-d6) δ 8.62 (d, J=3.0 Hz, 1H), 7.84 (ddd, J=9.0, 9.0, 3.0 Hz, 1H), 7.66 (dd, J=8.5, 4.5 Hz, 1H), 7.57 (d, J=8.0 Hz, 1H), 7.49 (d, J=8.0 Hz, 1H), 7.38 (dd, J=3.0, 1.5 Hz, 1H), 6.92-6.88 (m, 1H), 6.12 (dd, J=7.5, 3.0 Hz, 1H), 5.96 (d, J=2.5 Hz, 1H), 5.22 (s, 2H), 3.82-3.76 (m, 2H), 3.75-3.63 (m, 5H), 3.10 (t J=5.5, 1H), 3.05-2.98 (m, 2H), 2.93 (t, J=5.5, 1H), 2.13 (s, 1.5H), 2.08 (s, 1.5H); ESI MS m/z 461 [M+H]+.

Workup

  1. customthe resulting phases were separated
  2. dry with materialThe organic phase was dried over Na2SO4
  3. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-788d572d3c2b47ada93afdff1d823590
Source dataset
uspto-grants-2014_01
Patent number
US08637501B2

Reaction notes

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