Potassium Phosphate, Tribasic → 4-(2-Fluoro-4-trimethylsilanylphenylamino)-1-(toluene-4-sulfonyl)-1H-indazole-5-carboxylic acid methyl ester

HRID 79015Notes

Reaction equation

HRID 79015 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:6](Cl)=[C:7]2[C:11](=[CH:12][CH:13]=1)[N:10]([S:14]([C:17]1[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=1)(=[O:16])=[O:15])[N:9]=[CH:8]2)=[O:4].COC(=O)/C(=C(\Cl)/C1C(C)=NN(S(C2C=CC(C)=CC=2)(=O)=O)C=1)/C=C.[F:50][C:51]1[CH:56]=[C:55]([Si:57]([CH3:60])([CH3:59])[CH3:58])[CH:54]=[CH:53][C:52]=1[NH2:61].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:1][O:2][C:3]([C:5]1[C:6]([NH:61][C:52]2[CH:53]=[CH:54][C:55]([Si:57]([CH3:59])([CH3:58])[CH3:60])=[CH:56][C:51]=2[F:50])=[C:7]2[C:11](=[CH:12][CH:13]=1)[N:10]([S:14]([C:17]1[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=1)(=[O:16])=[O:15])[N:9]=[CH:8]2)=[O:4]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 595965992-Fluoro-4-(trimethylsilyl)anilineHCID 670841244-Chloro-1-(toluene-4-sulfonyl)-1H-indazole-5-carboxylic acid methyl esterHCID 872622922-[1-chloro-1-[3-methyl-1-(toluene-4-sulfonyl)-1H-pyrazol-4-yl]-meth-(Z)-ylidene]-but-3-enoic acid methyl ester

Product 1

HCID 670839874-(2-Fluoro-4-trimethylsilanylphenylamino)-1-(toluene-4-sulfonyl)-1H-indazole-5-carboxylic acid methyl esterYield 50%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
105 °C

Procedure

4-Chloro-1-(toluene-4-sulfonyl)-1H-indazole-5-carboxylic acid methyl ester and 2-[1-chloro-1-[3-methyl-1-(toluene-4-sulfonyl)-1H-pyrazol-4-yl]-meth-(Z)-ylidene]-but-3-enoic acid methyl ester (1.1 g, 3.0 mmol), 2-fluoro-4-trimethylsilanylphenylamine (0.61 g, 3.3 mmol), 2-dicyclohexylphosphino-2′-6′-diisopropyl biphenyl (0.28 g, 0.60 mmol), potassium phosphate (0.70 g, 3.3 mmol) and tris(dibenzylideneacetone)dipalladium (0) (87 mg, 0.15 mmol) were suspended in toluene (5 mL) and the resultant mixture degassed. The reaction mixture was heated at 105° C. for 3 hours. The reaction was quenched by the addition of hydrochloric acid (1M, 5 mL) and the resultant mixture extracted with ethyl acetate (3×20 mL). The combined organic extracts were washed with brine (20 mL), dried (MgSO4) and concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si—SPE, gradient 0-100% DCM in cyclohexane) to yield the title compound as a pale brown solid (0.78 g, 50%). 1H NMR showed the product to be a single isomer. LCMS (Method B): RT=5.22 min, [M+H]+=512.

Workup

  1. customthe resultant mixture degassed
  2. customThe reaction was quenched by the addition of hydrochloric acid (1M, 5 mL)
  3. extractionthe resultant mixture extracted with ethyl acetate (3×20 mL)
  4. washThe combined organic extracts were washed with brine (20 mL)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-304e2d60bf064880b12e7a6abdcfbff8
Source dataset
uspto-grants-2014_09
Patent number
US08841462B2

Reaction notes

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