Dimethylformamide → 7H-indolo[2,1-a][2]benzazepine-6,10-dicarboxamide

HRID 1453380Notes

Reaction equation

[CH:1]1[C:11]2[C:10]3=[CH:12][C:13]4[CH:14]=[CH:15][C:16]([C:19](O)=[O:20])=[CH:17][C:18]=4[N:9]3[CH2:8][CH:7]=[CH:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.C[N:23](C)S(N)(=O)=O.N=C=N.C[N:33](C)[CH:34]=[O:35]>CN(C1C=CN=CC=1)C>[CH:1]1[C:11]2[C:10]3=[CH:12][C:13]4[CH:14]=[CH:15][C:16]([C:19]([NH2:23])=[O:20])=[CH:17][C:18]=4[N:9]3[CH2:8][C:7]([C:34]([NH2:33])=[O:35])=[CH:6][C:5]=2[CH:4]=[CH:3][CH:2]=1

Participants

Conditions

Temperature: 45 °C

Procedure

To a solution of 7H-indolo[2,1-a][2]benzazepine-10-carboxylic acid, 13-cyclohexyl-3-methoxy-6-[[methyl[2-(4-morpholinyl)-2-oxoethyl]amino]carbonyl]- (106 mg, 0.19 mmol), N,N-dimethylsulfamide (70 mg, 0.56 mmol) and DMAP (70 mg, 0.56 mmol) in dimethylformamide (1.2 mL) was added PS-carbodiimide (428 mg, 1.3 mmol/g, 0.56 mmol). The reaction solution was shaken at 45° C. for 6 h, filtered, concentrated and purified by preparative HPLC (MeOH/H2O with an NH4OAc buffer) to yield 7H-indolo[2,1-a][2]benzazepine-6,10-dicarboxamide, 13-cyclohexyl-N10-[(dimethylamino)sulfonyl]-3-methoxy-N6-methyl-N6-[2-(4-morpholinyl)-2-oxoethyl]- (26 mg, 0.04 mmol, 21%) as a yellow solid. Mixture of amide rotamers: 1HNMR (300 MHz, CD3OD) δ 8.25-8.08 (m, 1H), 7.92 (d, J=8.4 Hz, 1H), 7.64-7.52 (m, 2H), 7.20-6.95 (m, 3H), 5.30-5.04 (m, 1H), 4.59-4.27 (m, 3H), 3.93 (s, 3H), 3.78-3.48 (m, 4H), 3.33 (s, 3H), 3.03 (s, 6H), 3.10-2.82 (m, 5H), 2.21-1.72 (m, 6H), 1.58-1.21 (m, 4H). LCMS: m/e 678 (M+H)+, ret time 3.52 min, column B, 4 minute gradient.

Workup

filtrationfiltered
concentrationconcentrated
custompurified by preparative HPLC (MeOH/H2O with an NH4OAc buffer)

Sources & evidence

ORD record: ord-5a8b8246ed504c9abf398927a3bb9cc3
Source dataset: uspto-grants-2009_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07473688B2

Reaction notes

Loading…