Water → (RS)-1-[2-(4-Acetyl-1H-benzoimidazol-2-ylmethyl)-piperidin-1-yl]-1-[5-(4-fluorophenyl)-2-methylthiazol-4-yl]methanone

HRID 1367032Notes

Reaction equation

HRID 1367032 reaction equation
Br[C:2]1[C:10]2[N:9]=[C:8]([CH2:11][CH:12]3[CH2:17][CH2:16][CH2:15][CH2:14][N:13]3[C:18]([C:20]3[N:21]=[C:22]([CH3:32])[S:23][C:24]=3[C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)=[O:19])[NH:7][C:6]=2[CH:5]=[CH:4][CH:3]=1.C([Sn](CCCC)(CCCC)[C:38]([O:40]CC)=[CH2:39])CCC.O>O1CCOCC1.Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:38]([C:2]1[C:10]2[N:9]=[C:8]([CH2:11][CH:12]3[CH2:17][CH2:16][CH2:15][CH2:14][N:13]3[C:18]([C:20]3[N:21]=[C:22]([CH3:32])[S:23][C:24]=3[C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)=[O:19])[NH:7][C:6]=2[CH:5]=[CH:4][CH:3]=1)(=[O:40])[CH3:39]

Participants

7

Reactant 3

HCID 962Water2×HCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 17973675HCID 17973675, compound

Product 1

HCID 17973678(RS)-1-[2-(4-Acetyl-1H-benzoimidazol-2-ylmethyl)-piperidin-1-yl]-1-[5-(4-fluorophenyl)-2-methylthiazol-4-yl]methanoneYield 33%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidCatalystHCID 178418397HCID 178418397, compoundCatalyst2×HCID 312751,4-DioxaneSolvent

Procedure

To a deoxygenated solution of (RS)-1-[2-(4-bromo-1H-benzoimidazol-2-ylmethyl)-piperidin-1-yl]-1-[5-(4-fluorophenyl)-2-methylthiazol-4-yl]methanone, E66 (200 mg, 0.39 mmol) in anhydrous 1,4-dioxane (10 ml) was added tributyl(1-ethoxyvinyl)tin (155 mg, 0.43 mmol) and tetrakis(triphenylphosphine)palladium(0) (30 mg, 0.026 mmol). The resultant mixture was refluxed under argon for 20 h. Further tetrakis(triphenylphosphine)palladium(0) (60 mg, 0.052 mmol) was added and refluxing continued for a further 24 h. On cooling, water (15 ml) and 5N hydrochloric acid (10 drops) were added and the mixture stirred at room temperature for 2 h. The reaction mixture was poured into water and extracted with ethyl acetate (3×). The combined organics were dried (Na2SO4) and the solvent removed in vacuo. Chromatography (silica gel, 0-100% ethyl acetate-hexane then 2-5% methanol-ethyl acetate) afforded the title compound as a pale orange solid (62 mg, 33%).

Workup

  1. temperaturerefluxing
  2. temperatureOn cooling
  3. extractionextracted with ethyl acetate (3×)
  4. dry with materialThe combined organics were dried (Na2SO4)
  5. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-dbebaabbf6ae4beebd33351f0b8552ea
Source dataset
uspto-grants-2011_02
Patent number
US07893090B2

Reaction notes

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