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

HRID 1453351Notes

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-(2-pyrimidinyl)-1-piperazinyl]carbonyl] (125 mg, 0.23 mmol), N,N-dimethylsulfamide (140 mg, 1.14 mmol) and DMAP (140 mg, 1.14 mmol) in dimethylacetamide (2 mL) was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (175 mg, 0.91 mmol). The reaction solution was stirred at 50° C. overnight, concentrated, purified by preparative HPLC (MeOH/2O with NH4OAc buffer) and repurified by preparative HPLC (MeOH/2O with TFA buffer) to yield 7H-indolo[2,1-a][2]benzazepine-10-carboxamide, 13-cyclohexyl-N-[(dimethylamino)sulfonyl]-6-[[4-(2-pyrimidinyl)-1-piperazinyl]carbonyl] (44 mg, 0.067 mol, 29%) as a yellow solid. 1H NMR (500 MHz, CDCl3) δ 9.23 (br s, 1H), 8.43 (d, J=4.9 Hz, 2H), 8.04 (s, 1H), 7.92 (d, J=8.5 Hz, 1H), 7.60 (br d, J=8.5 Hz, 1H), 7.54-7.45 (m, 3H), 7.42 (br d, J=7.6 Hz, 1H), 6.92 (s, 1H), 6.68 (t, J=4.9 Hz, 1H), 5.16 (br s, 1H), 4.41 (br s, 1H), 3.88-3.46 (m, 8H), 3.03 (s, 6H), 2.90-2.81 (m, 1H), 2.16-1.13 (m, 10H). LCMS: m/e 654 (M+H)+, ret time 2.87 min, column B, 2 minute gradient.

Workup

concentrationconcentrated
custompurified by preparative HPLC (MeOH/2O with NH4OAc buffer)
customrepurified by preparative HPLC (MeOH/2O with TFA buffer)

Sources & evidence

ORD record: ord-af0035d535ca49569cf79e6ec1bcb98a
Source dataset: uspto-grants-2009_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07473688B2

Reaction notes

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