Potassium Carbonate → 1-(2-Methyl-pentanoyl)-piperidine-3-carboxylic acid [2-(5-fluoro-pyridin-3-yl)-4-methyl-thiazol-5-yl]-methyl-amide

HRID 533332Notes

Reaction equation

HRID 533332 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[S:9][C:10]([N:14]([CH3:23])[C:15]([CH:17]3[CH2:22][CH2:21][CH2:20][NH:19][CH2:18]3)=[O:16])=[C:11]([CH3:13])[N:12]=2)[CH:5]=[N:6][CH:7]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:30][CH:31]([CH2:35][CH2:36][CH3:37])[C:32](Cl)=[O:33]>CN(C1C=CN=CC=1)C.ClCCCl.O.ClCCl>[F:1][C:2]1[CH:3]=[C:4]([C:8]2[S:9][C:10]([N:14]([CH3:23])[C:15]([CH:17]3[CH2:22][CH2:21][CH2:20][N:19]([C:32](=[O:33])[CH:31]([CH3:30])[CH2:35][CH2:36][CH3:37])[CH2:18]3)=[O:16])=[C:11]([CH3:13])[N:12]=2)[CH:5]=[N:6][CH:7]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 1073852-Methylvaleryl chlorideHCID 59580768N-(2-(5-fluoropyridin-3-yl)-4-methylthiazol-5-yl)-N-methylpiperidine-3-carboxamide

Product 1

HCID 595806541-(2-Methyl-pentanoyl)-piperidine-3-carboxylic acid [2-(5-fluoro-pyridin-3-yl)-4-methyl-thiazol-5-yl]-methyl-amideYield 64%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 111,2-DichloroethaneSolventHCID 21908982Water methylene chlorideSolvent

Procedure

A solution of N-(2-(5-fluoropyridin-3-yl)-4-methylthiazol-5-yl)-N-methylpiperidine-3-carboxamide (250 mg, 0.75 mmol), DMAP (91 mg, 0.75 mmol), potassium carbonate (310 mg, 2.243 mmol), and 2-methylpentanoyl chloride (201 mg, 1.495 mmol) in DCE (10 mL) was heated at 80° C. for 6 h. The cooled contents were diluted with water:dichloromethane (1:1, 20 mL) and the organic layer was collected and concentrated. The residue was purified via reversed phase chromatography (0 to 100% acetonitrile/water) to furnish the title compound as a clear oil (207 mg, 64%): 1H NMR (400 MHz, CDCl3) δ 8.89 (s, 1H), 8.54 (d, J=2.2 Hz, 1H), 7.96 (dt, J=9.0, 2.2 Hz, 1H), 4.63-4.59 (m, 1H), 3.92-3.78 (m, 1H), 3.42 (s, 3H), 2.66-2.48 (m, 4H), 2.38 (s, 3H), 1.89-1.73 (m, 2H), 1.71-1.68 (m, 2H), 1.38-1.17 (m, 4H), 1.08-1.01 (m, 3H), 0.97-0.86 (m, 3H); ESIMS m/z 433 (M+1).

Workup

  1. customthe organic layer was collected
  2. concentrationconcentrated
  3. customThe residue was purified

Sources & evidence

ORD record
ord-f96aa5c386e241b7a0804ed8f5a95c7a
Source dataset
uspto-grants-2014_10
Patent number
US08853246B2

Reaction notes

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