Acetic Acid → 2,4,6-Trifluoro-N-[6-(1-propyl-piperidin-4-yloxy)-pyridin-2-yl]-benzamide

HRID 1822038Notes

Reaction equation

HRID 1822038 reaction equation
[F:1][C:2]1[CH:23]=[C:22]([F:24])[CH:21]=[C:20]([F:25])[C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([O:13][CH:14]2[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)[N:8]=1)=[O:5].[CH:26](=O)[CH2:27][CH3:28].C(O)(=O)C>C1COCC1>[F:25][C:20]1[CH:21]=[C:22]([F:24])[CH:23]=[C:2]([F:1])[C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([O:13][CH:14]2[CH2:15][CH2:16][N:17]([CH2:26][CH2:27][CH3:28])[CH2:18][CH2:19]2)[N:8]=1)=[O:5]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 527PropanalHCID 578937702,4,6-Trifluoro-N-[6-(piperidin-4-yloxy)pyridin-2-yl]-benzamide

Product 1

HCID 578936712,4,6-Trifluoro-N-[6-(1-propyl-piperidin-4-yloxy)-pyridin-2-yl]-benzamideYield 69%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Combine 2,4,6-trifluoro-N-[6-(piperidin-4-yloxy)pyridin-2-yl]-benzamide (example 84, 250 mg, 0.71 mmol), propionaldehyde (124 mg, 2.14 mmol), acetic acid (85 mg, 1.42 mmol), molecular sieve 4 Å (0.4 g) and THF (6 mL), stir for 15 min. Then add NaBH(tri-acetate) portionwise and stir for 3 hr. 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 5% 2M NH3-methanol in methylene dichloride provides 192 mg (69%) of the title compound: mass spectrum (ion spray): m/z=394.1 (M+1); 1H NMR (CDCl3, ppm): 8.00 (s, br, 1H), 7.84 (d, br, 1H), 7.64 (t, 1H), 6.78 (m, 2H), 6.52 (d, 1H), 4.94 (m, 1H), 2.75 (m, 2H), 2.32 (m, 4H), 2.04 (m, 2H), 1.85 (m, 2H), 1.55 (m, 2H), 0.92 (t, 3H). Mono-hydrochloride salt: Anal calcd for C20H22F3N3O2.HCl.0.25H2O: C, 55.30; H, 5.45; N, 9.67. Found: C, 55.13; H, 5.36; N, 9.61.

Workup

  1. customQuench
  2. customthe reaction with 0.1N NaOH
  3. extractionextract with methylene dichloride three times
  4. dry with materialCombine the organic layers, dry over Na2SO4
  5. filtrationfilter
  6. concentrationconcentrate
  7. customto give a residue
  8. washChromatography (silica gel) eluting with 5% 2M NH3-methanol in methylene dichloride

Sources & evidence

ORD record
ord-1a2733d0f3454470897c8ed32b5bb889
Source dataset
uspto-grants-2009_10
Patent number
US07608629B2

Reaction notes

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