Trifluoroacetic acid → 6-(Piperidin-4-ylamino)-pyridine-3-sulfonic acid (4-fluoro-phenyl)-isobutyl-amide

HRID 1049025Notes

Reaction equation

HRID 1049025 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:35])(=[O:34])[N:22]([C:27]3[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=3)[CH2:23][CH:24]([CH3:26])[CH3:25])=[CH:17][N:16]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:33][C:30]1[CH:31]=[CH:32][C:27]([N:22]([CH2:23][CH:24]([CH3:26])[CH3:25])[S:21]([C:18]2[CH:17]=[N: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:35])=[O:34])=[CH:28][CH:29]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 867218764-{5-[(4-Fluoro-phenyl)-isobutyl-sulfamoyl]-pyridin-2-ylamino}-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 867218776-(Piperidin-4-ylamino)-pyridine-3-sulfonic acid (4-fluoro-phenyl)-isobutyl-amideYield 77.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-{5-[(4-fluoro-phenyl)-isobutyl-sulfamoyl]-pyridin-2-ylamino}-piperidine-1-carboxylic acid tert-butyl ester (66 mg, 130 μmol) in DCM (8 mL) was added TFA (2 mL) and the reaction was stirred at room temperature for 30 minutes. The reaction was concentrated and purified by SCX column eluting with 2M NH3 in MeOH to give 6-(piperidin-4-ylamino)-pyridine-3-sulfonic acid (4-fluoro-phenyl)-isobutyl-amide (41 mg, 101 μmol). To a solution of 6-(piperidin-4-ylamino)-pyridine-3-sulfonic acid (4-fluoro-phenyl)-isobutyl-amide (41 mg, 101 μmol) in DCM (5 mL) was added DIPEA (35 μL, 202 μmol) followed by methane sulfonylchloride (1 mL of a 78 μL, 1 mmol solution in 10 mL of DCM) and the reaction stirred at room temperature for 30 minutes. Water and saturated NaHCO3 were then added, extracted, filtered through a phase separator, concentrated and purified by silica gel column chromatography (0-50% EtOAc in cyclohexane) to give the title compound (49 mg). 1H NMR (400 MHz, DMSO): δ 8.03 (d, J=2.52 Hz, 1H), 7.54 (d, J=7.47 Hz, 1H), 7.35 (dd, J=8.95, 2.54 Hz, 1H), 7.17 (t, J=8.01 Hz, 4H), 6.51 (d, J=8.98 Hz, 1H), 3.91 (br s, 1H), 3.51 (d, J=11.88 Hz, 2H), 3.25 (d, J=7.31 Hz, 2H), 2.86 (m, 5H), 1.97 (d, J=12.65 Hz, 2H), 1.44-1.49 (m, 2H), 0.82 (d, J=6.63 Hz, 6H). LCMS (m/z, Method B) ES+ 485.0 [M+1]+.

Workup

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

Sources & evidence

ORD record
ord-4552b048f79a4d3faa4cb436dec18dee
Source dataset
uspto-grants-2016_07
Patent number
US09382222B2

Reaction notes

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