Trifluoroacetic acid → HCID 86721867, compound

HRID 1049007Notes

Reaction equation

HRID 1049007 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([S:21](=[O:36])(=[O:35])[N:22]([CH2:27][C:28]3[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=3)[CH2:23][CH:24]([CH3:26])[CH3:25])=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:34][C:31]1[CH:30]=[CH:29][C:28]([CH2:27][N:22]([CH2:23][CH:24]([CH3:25])[CH3:26])[S:21]([C:18]2[CH:17]=[CH:16][C:15]([NH:14][CH:11]3[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]3)=[CH:20][CH:19]=2)(=[O:36])=[O:35])=[CH:33][CH:32]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86721866HCID 86721866, compound

Product 1

HCID 86721867HCID 86721867, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-{4-[(4-fluoro-benzyl)-isobutyl-sulfamoyl]-phenylamino}-piperidine-1-carboxylic acid tert-butyl ester (208 mg) in DCM (9 mL) was added TFA (1 mL) and the reaction was stirred at room temperature for 30 minutes. The reaction was concentrated and purified by SCX column eluting with 2 M NH3 in MeOH to give N-(4-fluoro-benzyl)-N-isobutyl-4-(piperidin-4-ylamino)-benzenesulfonamide. A solution of the crude product (149 mg) in DCM (5 mL) was added DIPEA (124 μL, 711 μmol) followed by methane sulfonylchloride (28 μL, 356 μmol) and the reaction stirred at room temperature for 30 minutes. Water was then added, passed through a phase separator, extracted once more through a phase separator, concentrated and purified by silica gel column chromatography (0-75% EtOAc in cyclohexane) to give the title compound (139 mg). 1H NMR (400 MHz, DMSO): δ 7.51 (d, J=8.7 Hz, 2H), 7.4 (dd, J=8.5, 5.6 Hz, 2H), 7.15 (t, J=8.8 Hz, 2H), 6.71 (d, J=8.7 Hz, 2H), 6.55 (d, J=7.8 Hz, 1H), 4.15 (s, 2H), 3.48-3.53 (m, 3H), 2.93 (d, J=11.6 Hz, 2H), 2.89 (s, 3H), 2.76 (d, J=7.4 Hz, 2H), 1.99 (m, 2H), 1.44-1.49 (m, 3H), 0.65 (d, J=6.6 Hz, 6H). LCMS (m/z, Method B) ES+ 498.0 [M+1]+.

Workup

  1. concentrationThe reaction was concentrated
  2. custompurified by SCX column
  3. washeluting with 2 M NH3 in MeOH

Sources & evidence

ORD record
ord-a5cf7e5dbf244102912810aa79f4e838
Source dataset
uspto-grants-2016_07
Patent number
US09382222B2

Reaction notes

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