Triethylamine → 2,4,6-Trifluoro-N-ethyl-N-[6-(1-methyl-piperidin-4-yloxy)-pyridin-2-yl]-benzamide

HRID 1822056Notes

Reaction equation

[CH2:1]([NH:3][C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([O:10][CH:11]2[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]2)[N:5]=1)[CH3:2].C(N(CC)CC)C.[F:25][C:26]1[CH:34]=[C:33]([F:35])[CH:32]=[C:31]([F:36])[C:27]=1[C:28](Cl)=[O:29]>C1COCC1>[F:25][C:26]1[CH:34]=[C:33]([F:35])[CH:32]=[C:31]([F:36])[C:27]=1[C:28]([N:3]([CH2:1][CH3:2])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([O:10][CH:11]2[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]2)[N:5]=1)=[O:29]

Participants

Conditions

Temperature: 55 °C

Procedure

Dissolve ethyl-[6-(1-methyl-piperidin-4-yloxy)-pyridin-2-yl]-amine (preparation 74, 110 mg, 0.47 mmol) in THF (6 mL), add triethylamine (95 mg, 0.94 mmol) and 2,4,6-trifluorobenzoyl chloride (136 mg, 0.70 mmol) sequentially, heat at 55° C. overnight. Quench the reaction with 0.1N NaOH, extract with methylene dichloride three times. Combine the organic layers, dry over Na2SO4, filter and concentrate to give a residue. Chromatography (silica gel) eluting with 3.5% 2M NH3-methanol in methylene dichloride provides 151 mg (82%) of the title compound as an oil: mass spectrum (ion spray): m/z=394.1 (M+1); 1H NMR (CDCl3, ppm): 7.43 (t, 1H), 6.52 (m, 4H), 4.82 (m, 1H), 4.03 (q, 2H), 2.73 (m, 2H), 2.33 (s, 3H), 2.26 (m, 2H), 1.95 (m, 2H), 1.75 (m, 2H), 1.31 (t, 3H). Mono-hydrochloride salt: Anal calcd for C20H22F3N3O2.HCl.H2O: C, 53.63; H, 5.63; N, 9.38. Found: C, 53.66; H, 5.12; N, 9.29.

Workup

customQuench
customthe reaction with 0.1N NaOH
extractionextract with methylene dichloride three times
dry with materialCombine the organic layers, dry over Na2SO4
filtrationfilter
concentrationconcentrate
customto give a residue
washChromatography (silica gel) eluting with 3.5% 2M NH3-methanol in methylene dichloride

Sources & evidence

ORD record: ord-a16358d998d34967989b385a55cee543
Source dataset: uspto-grants-2009_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07608629B2

Reaction notes

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