Diisopropylethylamine → 4-{5-[(4-Fluoro-phenyl)-isobutyl-sulfamoyl]-pyridin-2-ylamino}-piperidine-1-carboxylic acid tert-butyl ester

HRID 1049024Notes

Reaction equation

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

Participants

Conditions

Temperature: 160 °C

Procedure

To a solution of 6-chloro-pyridine-3-sulfonic acid (4-fluoro-phenyl)-isobutyl-amide (150 mg, 439 μmol) and 4-amino-1-boc piperidine (114 mg, 570 μmol) in acetonitrile (3 mL) was added DIPEA (115 μl, 658 μmol) and the reaction was heated at 160° C. in a microwave reactor for 2.5 hours. EtOAc and saturated aqueous NaHCO3 were added, extracted, washed with brine, dried with Na2SO4 then concentrated and purified by silica gel column chromatography (0-50% EtOAc in cyclohexane) to give 4-{5-[(4-fluoro-phenyl)-isobutyl-sulfamoyl]-pyridin-2-ylamino}-piperidine-1-carboxylic acid tert-butyl ester (69 mg, 31%). LCMS (m/z, Method A) ES− 506 [M−1]−.

Workup

extractionextracted
washwashed with brine
dry with materialdried with Na2SO4
concentrationthen concentrated
custompurified by silica gel column chromatography (0-50% EtOAc in cyclohexane)

Sources & evidence

ORD record: ord-9e998b1fde03419e8ab94903b300f7a4
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09382222B2

Reaction notes

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