Triethylamine → HCID 44628251, compound

HRID 2189493Notes

Reaction equation

HRID 2189493 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:35])([F:34])[C:21]([C:23]1[CH:28]=[CH:27][C:26]([O:29][C:30]([F:33])([F:32])[F:31])=[CH:25][CH:24]=1)=O.C(N(CC)CC)C.C([BH3-])#N.[Na+]>C(Cl)Cl.CO.[Ti](Cl)(Cl)(Cl)Cl>[CH:1]1([NH:4][C:5]([C:6]2[N:7]=[C:8]([C:12]3[CH2:13][CH2:14][N:15]([CH:21]([C:23]4[CH:24]=[CH:25][C:26]([O:29][C:30]([F:31])([F:32])[F:33])=[CH:27][CH:28]=4)[C:20]([F:35])([F:34])[F:19])[CH2:16][CH:17]=3)[CH:9]=[CH:10][CH:11]=2)=[O:18])[CH2:3][CH2:2]1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 5003444Sodium cyanoborohydrideHCID 13880754HCID 13880754, compoundHCID 58296110HCID 58296110, compound

Product 1

HCID 44628251HCID 44628251, compoundYield 26.3%

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

Titanium (IV) chloride (0.098 ml, 0.887 mmol) was added to a solution of N-cyclopropyl-6-(1,2,3,6-tetrahydropyridin-4-yl)picolinamide free base (5b) (432 mg, 1.77 mmol), 2,2,2-trifluoro-1-(4-trifluoromethoxyphenyl)ethanone (63) (458 mg, 1.77 mmol) and triethylamine (0.492 ml, 3.55 mmol) in CH2Cl2 (12 ml) and stirred at room temperature for 18 hours. Sodium cyanoborohydride (334 mg, 5.32 mmol) in methanol (4 ml) was added to the reaction mixture and stirred for 19 hours. The reaction was quenched with aqueous NaOH solution (2 N), extracted with CH2Cl2, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography (ethyl acetate/hexane: 67/33) to give 1′-[2,2,2-trifluoro-1-(4-trifluoromethoxyphenyl)ethyl]-1′,2′,3′,6′-tetrahydro-[2,4′]bipyridinyl-6-carboxylic acid cyclopropylamide (64) (226 mg, yield 26%) as a pale orange oil. 1H NMR (400 MHz, CDCl1): S 8.04 (m, 1H), 8.00 (brs, 1H), 7.77 (t, J=7.8 Hz, 1H), 7.47 (m, 3H), 7.26 (m, 2H), 6.58 (m, 1H), 4.21 (q, J=7.9 Hz, 1H), 3.45 (m, 2H), 2.97 (m, 1H), 2.90 (m, 1H), 2.80 (m, 1H), 2.66 (m, 2H), 0.88 (m, 2H), 0.65 (m, 2H); MS: 486 (M+H+).

Workup

  1. stirringstirred for 19 hours
  2. customThe reaction was quenched with aqueous NaOH solution (2 N)
  3. extractionextracted with CH2Cl2
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography (ethyl acetate/hexane: 67/33)

Sources & evidence

ORD record
ord-28f5b7a9c75f4e7e93bffe8b51101680
Source dataset
uspto-grants-2012_12
Patent number
US08324249B2

Reaction notes

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