Carbon Dioxide → 2-bromo-3-cyclohexyl-N-(dimethylsulfamoyl)-1H-indole-6-carboxamide

HRID 1723942Notes

Reaction equation

C(N1C=CN=C1)(N1C=CN=C1)=O.[Br:13][C:14]1[NH:15][C:16]2[C:21]([C:22]=1[CH:23]1[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1)=[CH:20][CH:19]=[C:18]([C:29]([OH:31])=O)[CH:17]=2.C(=O)=O.[CH3:35][N:36]([CH3:41])[S:37]([NH2:40])(=[O:39])=[O:38].C1CCN2C(=NCCC2)CC1>C1COCC1>[Br:13][C:14]1[NH:15][C:16]2[C:21]([C:22]=1[CH:23]1[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1)=[CH:20][CH:19]=[C:18]([C:29]([NH:40][S:37]([N:36]([CH3:41])[CH3:35])(=[O:39])=[O:38])=[O:31])[CH:17]=2

Participants

Conditions

Temperature: 50 °C

Procedure

1,1′-Carbonyldiimidazole (1.17 g, 7.2 mmol) was added to a stirred solution of 2-bromo-3-cyclohexyl-1H-indole-6-carboxylic acid (2.03 g, 6.3 mmol) in THF (6 mL) at 22° C. The evolution of CO2 was instantaneous and when it slowed the solution was heated at 50° C. for 1 hr and then cooled to 22° C. N,N-Dimethylsulfamide (0.94 g, 7.56 mmol) was added followed by the dropwise addition of a solution of DBU (1.34 g, 8.8 mmol) in THF (4 mL). Stirring was continued for 24 hr. The mixture was partitioned between ethyl acetate and dilute HCl. The ethyl acetate layer was washed with water followed by brine and dried over Na2SO4. The extract was concentrated to dryness to leave the title product as a pale yellow friable foam, (2.0 g, 74%, >90% purity, estimated from NMR). 1H NMR (300 MHz, DMSO-D6) δ ppm 1.28-1.49 (m, 3H) 1.59-2.04 (m, 7H) 2.74-2.82 (m, 1H) 2.88 (s, 6H) 7.57 (dd, J=8.42, 1.46 Hz, 1H) 7.74 (d, J=8.78 Hz, 1H) 7.91 (s, 1H) 11.71 (s, 1H) 12.08 (s, 1H).

Workup

temperaturecooled to 22° C
customThe mixture was partitioned between ethyl acetate and dilute HCl
washThe ethyl acetate layer was washed with water
dry with materialdried over Na2SO4
concentrationThe extract was concentrated to dryness

Sources & evidence

ORD record: ord-d67abb54365e4a50be6b136ef930999c
Source dataset: uspto-grants-2009_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07485633B2

Reaction notes

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