Triethylamine → 3-(2,2-Difluoro-benzo[1,3]dioxol-5-ylmethyl)-piperidine-1-carboxylic acid pyridin-3-ylamide

HRID 1909082Notes

Reaction equation

Cl.[F:2][C:3]1([F:19])[O:7][C:6]2[CH:8]=[CH:9][C:10]([CH2:12][CH:13]3[CH2:18][CH2:17][CH2:16][NH:15][CH2:14]3)=[CH:11][C:5]=2[O:4]1.CCN(CC)CC.C1([O:33][C:34](=O)[NH:35][C:36]2[CH:37]=[N:38][CH:39]=[CH:40][CH:41]=2)C=CC=CC=1>CC#N>[N:38]1[CH:39]=[CH:40][CH:41]=[C:36]([NH:35][C:34]([N:15]2[CH2:16][CH2:17][CH2:18][CH:13]([CH2:12][C:10]3[CH:9]=[CH:8][C:6]4[O:7][C:3]([F:2])([F:19])[O:4][C:5]=4[CH:11]=3)[CH2:14]2)=[O:33])[CH:37]=1

Participants

Conditions

Temperature: 35 °C

Procedure

To a solution of 3-[(2,2-difluoro-1,3-benzodioxol-5-yl)methyl]-piperidine hydrochloride (100 mg, 0.34 mmol) in CH3CN (2 mL) was added Et3N (0.07 mL, 0.52 mmol). To this reaction mixture, pyridin-3-yl-carbamic acid phenyl ester (77.0 mg, 1.05 mmol) was added and the reaction mixture was heated overnight at 35° C. The reaction mixture was then concentrated and the crude residue was purified (FCC, 2 N NH3 in MeOH/DCM) to give 3-(2,2-difluoro-benzo[1,3]dioxol-5-ylmethyl)-piperidine-1-carboxylic acid pyridin-3-ylamide (120 mg, 93%). MS (ESI+): calcd for C19H19F2N3O3 m/z 375.14, found 376.2 (M+H)+. 1H NMR (d4-methanol): 8.54 (d, J=2.3, 1H), 8.17-8.13 (m, 1H), 7.86 (ddd, J=8.4, 2.6, 1.4, 1H), 7.34-7.30 (m, 1H), 7.10-7.06 (m, 2H), 6.99 (dd, J=8.2, 1.5, 1H), 4.05-3.95 (m, 2H), 3.04-2.98 (m, 1H), 2.74-2.64 (m, 2H), 2.58-2.53 (m, 1H), 1.86-1.74 (m, 3H), 1.56-1.47 (m, 1H), 1.30-1.22 (m, 1H).

Workup

concentrationThe reaction mixture was then concentrated
customthe crude residue was purified (FCC, 2 N NH3 in MeOH/DCM)

Sources & evidence

ORD record: ord-e0d7780d7aad464ba902fbe8fecc705f
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08598356B2

Reaction notes

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