Potassium Iodide → 4-[[(1R,2S)-(2-Carbamoyl-cyclohexyl)-(4-chlorobenzenesulfonyl)-amino]-methyl]-N-ethyl benzamide

HRID 7052

Reaction equation

HRID 7052 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([S:14]([NH:17][C@H:18]2[CH2:23][CH2:22][CH2:21][CH2:20][C@H:19]2[C:24]([NH2:26])=[O:25])(=[O:16])=[O:15])=[CH:10][CH:9]=1.Cl[CH2:28][C:29]1[CH:39]=[CH:38][C:32]([C:33]([NH:35][CH2:36][CH3:37])=[O:34])=[CH:31][CH:30]=1.[I-].[K+]>CN(C=O)C.C(OCC)(=O)C>[C:24]([C@H:19]1[CH2:20][CH2:21][CH2:22][CH2:23][C@H:18]1[N:17]([CH2:28][C:29]1[CH:39]=[CH:38][C:32]([C:33]([NH:35][CH2:36][CH3:37])=[O:34])=[CH:31][CH:30]=1)[S:14]([C:11]1[CH:12]=[CH:13][C:8]([Cl:7])=[CH:9][CH:10]=1)(=[O:15])=[O:16])(=[O:25])[NH2:26]

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 10796Cesium carbonateHCID 220197154-(Chloromethyl)-N-ethylbenzamideHCID 69655699cis-2-(4-Chlorobenzenesulfonylamino)-cyclohexanecarboxylic acid amide

Product 1

HCID 112137374-[[(1R,2S)-(2-Carbamoyl-cyclohexyl)-(4-chlorobenzenesulfonyl)-amino]-methyl]-N-ethyl benzamideYield 40.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Cesium carbonate (1.4 mmol) was added to a solution of (1R,2S)-2-(4-Chlorobenzenesulfonylamino)-cyclohexanecarboxylic acid amide (0.62 mmol) in DMF (7 mL). 4-Chloromethyl-N-ethylbenzamide (0.76 mmol) was added to the mixture followed by potassium iodide (0.75 mmol). Reaction was stirred at room temperature overnight. Reaction mixture was diluted with ethyl acetate (20 mL) then was washed with water (2×15 mL). Organic layer was concentrated in vacuo. Residue was purified by preparatory HPLC (acetonitrile/water/trifluoroacetic acid). Proper fractions were combined. Acetonitrile was removed from the mixture in vacuo. Remaining aqueous was frozen and lyophilized to yield 4-[[(1R,2S)-(2-Carbamoyl-cyclohexyl)-(4-chlorobenzenesulfonyl)-amino]-methyl]-N-ethyl benzamide (120 mg) as a white solid in 40% yield.: 1H NMR (300 Mz, DMSO-d6) δ 8.40 (t, 1 H), 7.79 (d, 2 H, J=8.4), 7.70 (d, 2 H, J=8.4), 7.64 (d, 2 H, J=8.4 ), 7.32 (d, 2 H, J=8.1), 6.66 (s, 1 H), 4.68 (d, 1 H, J=17.2), 4.54 (d, 1 H, J=17.2), 3.85 (m, 1 H), 3.28 (m, 2 H), 2.78 (s, 1 H), 2.40 (m, 1 H), 1.78 (m, 1 H), 1.63 (m, 2 H), 1.42–1.17 (m, 3 H), 1.12 (t, 3 H), 0.92 (m, 1 H); MS m/e 500 (M+Na)+.

Workup

  1. customReaction
  2. customReaction mixture
  3. washthen was washed with water (2×15 mL)
  4. concentrationOrganic layer was concentrated in vacuo
  5. customResidue was purified by preparatory HPLC (acetonitrile/water/trifluoroacetic acid)
  6. customAcetonitrile was removed from the mixture in vacuo
  7. temperatureRemaining aqueous was frozen

Sources & evidence

ORD record
ord-7ccb572f47204e98991b3ed20fabe162
Source dataset
uspto-grants-2006_08
Patent number
US07084178B2

Linked notes

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