Acetic Acid → HCID 67218510, compound

HRID 2189498Notes

Reaction equation

HRID 2189498 reaction equation
[CH:1]1([NH:4][C:5](=[O:18])[C:6]2[CH:11]=[CH:10][CH:9]=[C:8]([C:12]3[CH2:13][CH2:14][NH:15][CH2:16][CH:17]=3)[N:7]=2)[CH2:3][CH2:2]1.[F:19][C:20]([F:29])([F:28])[C:21]1[CH:25]=[C:24]([CH:26]=O)[O:23][N:22]=1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[ClH:48]>O1CCCC1.C(OCC)(=O)C>[ClH:48].[CH:1]1([NH:4][C:5](=[O:18])[C:6]2[CH:11]=[CH:10][CH:9]=[C:8]([C:12]3[CH2:13][CH2:14][N:15]([CH2:26][C:24]4[O:23][N:22]=[C:21]([C:20]([F:29])([F:28])[F:19])[CH:25]=4)[CH2:16][CH:17]=3)[N:7]=2)[CH2:3][CH2:2]1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 5049666Sodium triacetoxyborohydrideHCID 14880837HCID 14880837, compoundHCID 58296110HCID 58296110, compound

Product 1

HCID 67218510HCID 67218510, compoundYield 14%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of N-cyclopropyl-6-(1,2,3,6-tetrahydropyridin-4-yl)picolinamide free base (5b) (133 mg, 0.545 mmol), 3-(trifluoromethyl)isoxazole-5-carbaldehyde (75) (270 mg, 0.818 mmol) and acetic acid (0.037 ml, 0.654 mmol) in tetrahydrofuran (5 ml) was stirred at room temperature for 1 hour. Sodium triacetoxyborohydride (347 mg, 1.636 mmol) was added to the reaction mixture and stirred at room temperature for 15 hours. The reaction was quenched with saturated NaHCO3 solution (10 ml), extracted with ethyl acetate (50 ml×3), washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by column chromatography (ethyl acetate/hexane: 75/25 to 85/15) to give the desired free base. This was diluted with ethyl acetate and HCl solution (4 N in 1,4-dioxane) was added to the solution. The resulted solid was triturated with hexane to give N-cyclopropyl-6-(1-((3-(trifluoromethyl)isoxazol-5-yl)methyl)-1,2,3,6-tetrahydropyridin-4-yl)picolinamide hydrochloride (76) (33 mg, yield 14%) as a pale yellow solid. 1H NMR (DMSO-d6): δ 8.52 (brs, 1H), 8.00 (m, 1H), 7.92 (m, 1H), 7.77 (m, 1H), 7.47 (m, 1H), 6.93 (s, 1H), 4.77 (m, 2H), 3.93 (m, 2H), 2.83-3.20 (m, 5H), 0.72 (m, 2H), 0.64 (m, 2H); MS: 393 (M+H+).

Workup

  1. stirringstirred at room temperature for 15 hours
  2. customThe reaction was quenched with saturated NaHCO3 solution (10 ml)
  3. extractionextracted with ethyl acetate (50 ml×3)
  4. washwashed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography (ethyl acetate/hexane: 75/25 to 85/15)
  9. customto give the desired free base
  10. additionwas added to the solution
  11. customThe resulted solid was triturated with hexane

Sources & evidence

ORD record
ord-79e49e1aa4a84caf89148d82ac5665ae
Source dataset
uspto-grants-2012_12
Patent number
US08324249B2

Reaction notes

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