N,N-Dimethylsulfamide → 7H-indolo[2,1-a][2]benzazepine-10-carboxamide

HRID 1453412Notes

Reaction equation

[CH:1]1[C:11]2[C:10]3=[CH:12][C:13]4[CH:14]=[CH:15][C:16]([C:19]([OH:21])=O)=[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.Cl.CN(C)CCCN=C=NCC>CN(C1C=CN=CC=1)C.CC(N(C)C)=O>[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:21])=[CH:17][C:18]=4[N:9]3[CH2:8][CH:7]=[CH:6][C:5]=2[CH:4]=[CH:3][CH:2]=1

Participants

Conditions

Temperature: 50 °C

Procedure

To a stirred solution of 7H-indolo[2,1-a][2]benzazepine-10-carboxylic acid, 13-cyclohexyl-6-[[4-(methylsulfonyl)-1-piperazinyl]carbonyl] (430 mg, 0.79 mmol), N,N-dimethylsulfamide (390 mg, 3.13 mmol) and DMAP (380 mg, 3.13 mmol) in dimethylacetamide (6 mL) was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (450 mg, 2.34 mmol). The reaction solution was stirred at 50° C. for 3 h, concentrated, purified by preparative HPLC (CH3CN/H2O with NH4OAc buffer) to yield 7H-indolo[2,1-a][2]benzazepine-10-carboxamide, 13-cyclohexyl-N-[(dimethylamino)sulfonyl]-6-[[4-(methylsulfonyl)-1-piperazinyl]carbonyl] (135 mg, 0.22 mol, 28%) as a yellow powder. 1HNMR (500 MHz, DMSO-d6) δ 11.65 (s, 1H), 8.41 (br s, 1H), 7.94 (d, J=8.5 Hz, 1H), 7.65 (dd, J=1.5, 8.5 Hz, 1H), 7.63-7.55 (m, 4H), 7.04 (s, 1H), 5.19 (br s, 1H), 4.34 (br s, 1H), 3.66-3.31 (m, 8H), 2.92 (s, 6H), 2.84 (s, 3H), 2.82-2.75 (m, 1H), 2.11-1.06 (m, 10H). LCMS: m/e 652(M−H)1, ret time 1.63 min, column A, 2 minute gradient.

Workup

concentrationconcentrated
custompurified by preparative HPLC (CH3CN/H2O with NH4OAc buffer)

Sources & evidence

ORD record: ord-fc8acd2e7cd747019d724b54ea242a40
Source dataset: uspto-grants-2009_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07473688B2

Reaction notes

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