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4-Bromoanisole → 1-(4-{4-[(4-Methoxyphenyl)ethynyl]-1,3-thiazol-2-yl}piperidin-1-yl)-2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethanone

HRID 549969
Notes
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Reaction equation

HRID 549969 reaction equation
C(N(CC)CC)C.[CH3:8][C:9]1[N:13]([CH2:14][C:15]([N:17]2[CH2:22][CH2:21][CH:20]([C:23]3[S:24][CH:25]=[C:26]([C:28]#[C:29][Si](C)(C)C)[N:27]=3)[CH2:19][CH2:18]2)=[O:16])[N:12]=[C:11]([C:34]([F:37])([F:36])[F:35])[CH:10]=1.Br[C:39]1[CH:44]=[CH:43][C:42]([O:45][CH3:46])=[CH:41][CH:40]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>CN(C)C=O.O.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.[Cu]I>[CH3:46][O:45][C:42]1[CH:43]=[CH:44][C:39]([C:29]#[C:28][C:26]2[N:27]=[C:23]([CH:20]3[CH2:21][CH2:22][N:17]([C:15](=[O:16])[CH2:14][N:13]4[C:9]([CH3:8])=[CH:10][C:11]([C:34]([F:36])([F:35])[F:37])=[N:12]4)[CH2:18][CH2:19]3)[S:24][CH:25]=2)=[CH:40][CH:41]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

9

Reactant 4

HCID 77304-BromoanisoleHCID 8471TriethylamineHCID 2724141Tetrabutylammonium FluorideHCID 671564122-[5-Methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]-1-(4-{4-[(trimethylsilyl)ethynyl]-1,3-thiazol-2-yl}piperidin-1-yl)ethanone

Product 1

HCID 671568341-(4-{4-[(4-Methoxyphenyl)ethynyl]-1,3-thiazol-2-yl}piperidin-1-yl)-2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethanone

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

Tetrakis(triphenylphosphine)palladium(0) (25 mg), copper(I) iodide (8 mg) and triethylamine (53 mg) are added to a solution of 2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]-1-(4-{4-[(trimethylsilyl)ethynyl]-1,3-thiazol-2-yl}piperidin-1-yl)ethanone (I-98, 200 mg) and 1-bromo-4-methoxybenzene (91 mg) in degassed N,N-dimethylformamide (2 ml). After warming to 85° C., tetra-n-butylammonium fluoride (1M in THF, 0.48 ml) is added dropwise. The reaction mixture is then diluted with water and extracted with ethyl acetate. The organic extracts are dried over sodium sulphate and concentrated under reduced pressure. After chromatographic purification, this gives 1-(4-{4-[(4-methoxyphenyl)ethynyl]-1,3-thiazol-2-yl}piperidin-1-yl)-2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethanone (84 mg).

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe organic extracts are dried over sodium sulphate
  3. concentrationconcentrated under reduced pressure
  4. customAfter chromatographic purification

Sources & evidence

ORD record
ord-57afe89b33f24e91a8be5564e352790f
Source dataset
uspto-grants-2011_05
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07943774B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes