Potassium Phosphate, Tribasic → 8-(4-Cyclobutyl-2-fluoro-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid methyl ester

HRID 2067031Notes

Reaction equation

HRID 2067031 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].[CH:15]1([C:19]2[CH:25]=[CH:24][C:22]([NH2:23])=[C:21]([F:26])[CH:20]=2)[CH2:18][CH2:17][CH2:16]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)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:23][C:22]1[CH:24]=[CH:25][C:19]([CH:15]2[CH2:18][CH2:17][CH2:16]2)=[CH:20][C:21]=1[F:26])=[O:4]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 595651864-Cyclobutyl-2-fluoroanilineHCID 59565199Methyl 8-chloroimidazo[1,5-a]pyridine-7-carboxylate

Product 1

HCID 595652108-(4-Cyclobutyl-2-fluoro-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid methyl esterYield 38%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of 8-chloro-imidazo[1,5-a]pyridine-7-carboxylic acid methyl ester (250 mg, 1.2 mmol), 4-cyclobutyl-2-fluoroaniline (230 mg, 1.4 mmol), Pd2dba3 (43 mg, 0.047 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (80 mg, 0.19 mmol) and K3PO4 (350 mg, 1.7 mmol) in toluene (5 ml) was degassed with argon for 10 minutes and then heated at 100° C. for 18 hours. The reaction mixture was then cooled to room temperature and filtered through hyflo®. The filtrate was concentrated in vacuo, and the resultant gum was subjected to flash chromatography (Si-PPC, eluting with 5% ethyl acetate in DCM) to afford the title compound as a yellow oil (150 mg, 38%). 1H NMR (CDC13): 7.95 (1H, s), 7.73 (1H, d, J=7.4 Hz), 7.23 (1H, t, J=8.6 Hz), 7.07 (1H, d, J=7.3 Hz), 7.01 (2H, m), 6.50 (1H, s), 3.90 (3H, s), 3.59 (1H, m), 2.39 (2H, m), 2.17 (2H, m), 2.06 (1H, m), 1.93 (1H, m).

Workup

  1. customwas degassed with argon for 10 minutes
  2. temperatureThe reaction mixture was then cooled to room temperature
  3. filtrationfiltered through hyflo®
  4. concentrationThe filtrate was concentrated in vacuo
  5. washthe resultant gum was subjected to flash chromatography (Si-PPC, eluting with 5% ethyl acetate in DCM)

Sources & evidence

ORD record
ord-567958cf69e44a039af485404e019c52
Source dataset
uspto-grants-2012_10
Patent number
US08293763B2

Reaction notes

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