Potassium Phosphate, Tribasic → HCID 59565213, compound

HRID 2067026Notes

Reaction equation

HRID 2067026 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].[Br:15][C:16]1[CH:22]=[CH:21][C:19]([NH2:20])=[C:18]([Cl:23])[CH:17]=1.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.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:20][C:19]1[CH:21]=[CH:22][C:16]([Br:15])=[CH:17][C:18]=1[Cl:23])=[O:4]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 6101694-Bromo-2-chloroanilineHCID 162179852-Dicyclohexylphosphino-2',6'-diisopropoxybiphenylHCID 59565199Methyl 8-chloroimidazo[1,5-a]pyridine-7-carboxylate

Product 1

HCID 59565213HCID 59565213, compoundYield 50%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A suspension of 8-chloro-imidazo[1,5-a]pyridine-7-carboxylic acid methyl ester (300 mg, 1.43 mmol), 4-bromo-2-chloroaniline (354 mg, 1.72 mmol), Pd2dba3 (65 mg, 0.07 mmol), 2-dicyclohexylphosphino-2′,6′-diisopropoxybiphenyl (131 mg, 0.28 mmol) and K3PO4 (424 mg, 2.00 mmol) in toluene (5 ml) was degassed and then heated at 110° 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 and brine, then 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. The resultant residue was subjected to flash chromatography (Si-PPC, gradient 0% to 100%, ethyl actetate in DCM) to afford the title compound as a yellow oil (271 mg, 50%). LCMS (method B): RT=3.65 min, [M+H]+=381/383.

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 and brine
  5. washwas eluted with methanol
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1af585ebf4b54b31aeb5f21a83039607
Source dataset
uspto-grants-2012_10
Patent number
US08293763B2

Reaction notes

Loading…