Diisopropylethylamine → 1-Methanesulfonyl-piperidine-4-carboxylic acid {4-[isobutyl-(2-trifluoromethyl-phenyl)-sulfamoyl]-phenyl}-amide

HRID 1049047Notes

Reaction equation

HRID 1049047 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]([CH2:22][CH:23]([CH3:25])[CH3:24])[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[C:18]([F:21])([F:20])[F:19])(=[O:10])=[O:9])=[CH:4][CH:3]=1.[CH3:26][S:27]([N:30]1[CH2:35][CH2:34][CH:33]([C:36](Cl)=[O:37])[CH2:32][CH2:31]1)(=[O:29])=[O:28].CCN(C(C)C)C(C)C>C(Cl)Cl>[CH2:22]([N:11]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[C:18]([F:21])([F:19])[F:20])[S:8]([C:5]1[CH:6]=[CH:7][C:2]([NH:1][C:36]([CH:33]2[CH2:34][CH2:35][N:30]([S:27]([CH3:26])(=[O:29])=[O:28])[CH2:31][CH2:32]2)=[O:37])=[CH:3][CH:4]=1)(=[O:10])=[O:9])[CH:23]([CH3:25])[CH3:24]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 121159931-Methanesulfonylpiperidine-4-carbonyl chlorideHCID 867218914-amino-N-isobutyl-N-(2-trifluoromethyl-phenyl)-benzenesulfonamide

Product 1

HCID 867218921-Methanesulfonyl-piperidine-4-carboxylic acid {4-[isobutyl-(2-trifluoromethyl-phenyl)-sulfamoyl]-phenyl}-amideYield 65.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 4-amino-N-isobutyl-N-(2-trifluoromethyl-phenyl)-benzenesulfonamide (100 mg, 0.268 mmol), 1-(methylsulfonyl)-4-piperidinecarbonyl chloride (108 mg, 0.48 mmol) and DIPEA (138 μL, 0.804 mmol) in DCM (8 mL) was stirred at room temperature for 3 hours. The mixture was diluted with DCM, washed with 1 N aqueous HCl, saturated aqueous NaHCO3, water and brine, dried over Na2SO4 and concentrated under vacuum. Purification by silica gel column chromatography (0-100% EtOAc in cyclohexane) and triturating with Et2O/pentane gave the title compound (98 mg, 65%). 1H NMR (400 MHz, DMSO δ 10.42 (s, 1H), 7.85 (d, J=8.8 Hz, 2H), 7.82 (dd, J=7.7, 1.9 Hz, 1H), 7.62-7.63 (m, 1H), 7.58 (d, J=8.8 Hz, 2H), 6.99 (d, J=7.8 Hz, 1H), 3.63 (d, J=11.8 Hz, 2H), 3.38-3.39 (m, 1H), 3.11 (dd, J=13.4, 4.7 Hz, 1H), 2.90 (s, 3H), 2.76-2.78 (m, 2H), 1.95 (d, J=13.5 Hz, 2H), 1.63-1.68 (m, 2H), 1.44-1.48 (m, 1H), 1.09 (t, J=7.0 Hz, 1H), 0.88 (d, J=6.5 Hz, 3H), 0.71 (d, J=6.7 Hz, 3H). LCMS (m/z, Method B) ES+ 562.0 [M+1]+.

Workup

  1. washwashed with 1 N aqueous HCl, saturated aqueous NaHCO3, water and brine
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated under vacuum
  4. customPurification by silica gel column chromatography (0-100% EtOAc in cyclohexane)
  5. customtriturating with Et2O/pentane

Sources & evidence

ORD record
ord-ede15370735e40ebb67e5976d86d4d88
Source dataset
uspto-grants-2016_07
Patent number
US09382222B2

Reaction notes

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