2-Vinylpyridine → 1-[4-[4-(4,5-dihydro-5-(2-pyridinyl)-3-isoxazolyl)-2-thiazolyl]-1-piperidinyl]-2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethanone

HRID 1528535Notes

Reaction equation

HRID 1528535 reaction equation
[CH3:1][C:2]1[N:6]([CH2:7][C:8]([N:10]2[CH2:15][CH2:14][CH:13]([C:16](=[S:18])[NH2:17])[CH2:12][CH2:11]2)=[O:9])[N:5]=[C:4]([C:19]([F:22])([F:21])[F:20])[CH:3]=1.Cl[CH2:24][C:25](=O)[C:26](Cl)=[N:27][OH:28].C(=O)(O)[O-].[Na+].[CH:36]([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][N:39]=1)=[CH2:37]>O1CCCC1.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C(#N)C>[N:39]1[CH:40]=[CH:41][CH:42]=[CH:43][C:38]=1[CH:36]1[O:28][N:27]=[C:26]([C:25]2[N:17]=[C:16]([CH:13]3[CH2:14][CH2:15][N:10]([C:8](=[O:9])[CH2:7][N:6]4[C:2]([CH3:1])=[CH:3][C:4]([C:19]([F:22])([F:20])[F:21])=[N:5]4)[CH2:11][CH2:12]3)[S:18][CH:24]=2)[CH2:37]1

Participants

8

Reactant 4

HCID 75212-VinylpyridineHCID 516892Sodium BicarbonateHCID 68330913-chloro-N-hydroxy-2-oxopropanimidoyl chloride2×HCID 580788971-[2-[5-Methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]-4-piperidinecarbothioamide2×

Product 1

HCID 687440581-[4-[4-(4,5-dihydro-5-(2-pyridinyl)-3-isoxazolyl)-2-thiazolyl]-1-piperidinyl]-2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethanone

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]-4-piperidinecarbothioamide (i.e. the product of Example 8, Step C) (200 mg, 0.6 mmol) in tetrahydrofuran (8 mL) was added 3-chloro-N-hydroxy-2-oxopropanimidoyl chloride (i.e. the product of Example 7, Step B) (93 mg, 0.6 mmol), followed by tetrabutylammonium bromide (15 mg, 0.05 mmol). The reaction mixture was heated at 50° C. for 4 h. The reaction mixture was cooled and concentrated under reduced pressure. To the resulting residue, acetonitrile (8 mL) and finely powdered sodium bicarbonate (151 mg, 1.0 mmol) were added followed by 2-ethenylpyridine (63 mg, 0.6 mmol), and the resulting mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure and purified by flash chromatography on a silica gel (20 g), Varian Bond Elute SI® column using 0 to 75% ethyl acetate in hexanes as eluant to give 80 mg of the title product, a compound of the present invention, as a yellow semi-solid.

Workup

  1. temperatureThe reaction mixture was cooled
  2. concentrationconcentrated under reduced pressure
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. custompurified by flash chromatography on a silica gel (20 g), Varian Bond
  5. washElute SI® column

Sources & evidence

ORD record
ord-c1174805974348bda7a8510920aaf825
Source dataset
uspto-grants-2015_07
Patent number
US09090604B2

Reaction notes

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