Benzenesulfonamide → HCID 9549238, compound

HRID 1006291Notes

Reaction equation

HRID 1006291 reaction equation
[C:1]1([S:7]([NH2:10])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.CN(C)CCCN=C=NCC.[CH3:23][O:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]2[C:39]3[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=3)[N:33]([CH2:40][C:41]3[CH:46]=[CH:45][CH:44]=[C:43]([C:47]([F:50])([F:49])[F:48])[CH:42]=3)[C:32]=2[C:51](O)=[O:52])=[CH:27][CH:26]=1>CN(C)C1C=CN=CC=1.ClCCl>[CH3:23][O:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]2[C:39]3[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=3)[N:33]([CH2:40][C:41]3[CH:46]=[CH:45][CH:44]=[C:43]([C:47]([F:48])([F:49])[F:50])[CH:42]=3)[C:32]=2[C:51]([NH:10][S:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)(=[O:9])=[O:8])=[O:52])=[CH:27][CH:26]=1

Participants

6

Reactant 3

HCID 7370BenzenesulfonamideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 22676813HCID 22676813, compound

Product 1

HCID 9549238HCID 9549238, compoundYield 78%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

Benzenesulfonamide (155 mg, 1.0 mmol), 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride (96 mg, 0.50 mmol), and 4-(dimethylamino)pyridine (20 mg, 0.16 mmol) were added to a stirred solution of 3-(4-methoxyphenyl)-1-{[3-(trifluoromethyl)phenyl]methyl}indole-2-carboxylic acid (Lit: WO94/14434, 213 mg, 0.50 mmol in dichloromethane (5 mL). The resulting mixture was stirred for 18 h and then quenched with hydrochloric acid (1N). The mixture was extracted with ethyl acetate (2×20 mL) and the combined organic extracts was washed with brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was purified with silica gel flash chromatography using hexane/ethyl acetate (2/1) as the eluant to give a white solid. It was further purified by trituration with diethyl ether to afford (3-(4-methoxyphenyl)-1-{[3-(trifluoromethyl)phenyl]methyl}indol-2-yl)-N-(phenylsulfonyl) carboxamide as a white solid (220 mg, 78%): mp>250° C.; MS (electrospray, MH+) calcd for C30H24F3N2O4S 565.1, found 565.0; 1H NMR (DMSO-d6) δ 7.51-8.31 (m, 17 H), 7.03 (br s, 1H), 6.17 (s, 2H), 4.36 (s, 3H).

Workup

  1. customquenched with hydrochloric acid (1N)
  2. extractionThe mixture was extracted with ethyl acetate (2×20 mL)
  3. washthe combined organic extracts was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified with silica gel flash chromatography
  7. customto give a white solid
  8. customIt was further purified by trituration with diethyl ether

Sources & evidence

ORD record
ord-96012d9053b441a6a0f6b57024830ac3
Source dataset
uspto-grants-2004_09
Patent number
US06787651B2

Reaction notes

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