Potassium Phosphate, Tribasic → HCID 59565225, compound

HRID 2067014Notes

Reaction equation

HRID 2067014 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][N:8]2[CH:11]=[N:12][CH:13]=[C:7]2[C:6]=1Cl)=[O:4].[F:15][C:16]1[CH:21]=[C:20]([S:22][CH3:23])[CH:19]=[CH:18][C:17]=1[NH2:24].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC(C)C)=CC=CC=2OC(C)C)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.ClCCl.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[CH:10]=[CH:9][N:8]2[CH:11]=[N:12][CH:13]=[C:7]2[C:6]=1[NH:24][C:17]1[CH:18]=[CH:19][C:20]([S:22][CH3:23])=[CH:21][C:16]=1[F:15])=[O:4]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 162179852-Dicyclohexylphosphino-2',6'-diisopropoxybiphenylHCID 220256172-Fluoro-4-(methylsulfanyl)anilineHCID 59565199Methyl 8-chloroimidazo[1,5-a]pyridine-7-carboxylate

Product 1

HCID 59565225HCID 59565225, compoundYield 39%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of 8-chloro-imidazo[1,5-a]pyridine-7-carboxylic acid methyl ester (223 mg, 1.06 mmol), 2-fluoro-4-methylsulfanyl-phenylamine (200 mg, 1.27 mmol), Pd2dba3 (39 mg, 0.04 mmol), 2-dicyclohexylphosphino-2′,6′-diisopropoxybiphenyl (79 mg, 0.17 mmol) and K3PO4 (315 mg, 1.48 mmol) in toluene (4 mL) was degassed and then heated at 100° C. for 18 hours. The reaction mixture was then cooled to room temperature and diluted with ethyl acetate. The resultant mixture was washed with water followed by brine, before being loaded onto a 10 g Isolute® SCX-2 cartridge which was eluted with methanol, and then a 2M solution of ammonia in methanol. The appropriate fractions were combined and concentrated in vacuo to give a residue. The residue was subjected to flash chromatography (Si-PPC, gradient 0% to 10%, ethyl actetate in dichloromethane) to afford the title compound as a yellow oil (136 mg, 39%). LCMS (method B): RT=3.26 min, [M+H]+=332.

Workup

  1. customwas degassed
  2. temperatureThe reaction mixture was then cooled to room temperature
  3. additiondiluted with ethyl acetate
  4. washThe resultant mixture was washed with water
  5. washwas eluted with methanol
  6. concentrationconcentrated in vacuo
  7. customto give a residue

Sources & evidence

ORD record
ord-39ce8e7a203246159a04b80be43208df
Source dataset
uspto-grants-2012_10
Patent number
US08293763B2

Reaction notes

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