Dimethylacetamide → (R)-4-((1-cyclobutylethyl)amino)-3-(4-(trifluoromethyl)benzyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile

HRID 81083

Reaction equation

HRID 81083 reaction equation
C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.Cl[C:36]1[N:41]=[C:40]([NH:42][C@@H:43]([CH:45]2[CH2:48][CH2:47][CH2:46]2)[CH3:44])[C:39]2[N:49]([CH2:52][C:53]3[CH:58]=[CH:57][C:56]([C:59]([F:62])([F:61])[F:60])=[CH:55][CH:54]=3)[CH:50]=[N:51][C:38]=2[CH:37]=1.C[C:64]([N:66](C)C)=O>[CH2-]C=C.[CH2-]C=C.Cl[Pd+].Cl[Pd+].[C-]#N.[Zn+2].[C-]#N>[CH:45]1([C@H:43]([NH:42][C:40]2[C:39]3[N:49]([CH2:52][C:53]4[CH:54]=[CH:55][C:56]([C:59]([F:61])([F:60])[F:62])=[CH:57][CH:58]=4)[CH:50]=[N:51][C:38]=3[CH:37]=[C:36]([C:64]#[N:66])[N:41]=2)[CH3:44])[CH2:48][CH2:47][CH2:46]1

Participants

6

Reactant 3

HCID 31374Dimethylacetamide2×HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 86724459(R)-6-chloro-N-(1-cyclobutylethyl)-3-(4-(trifluoromethyl)benzyl)-3H-imidazo[4,5-c]pyridin-4-amine

Product 1

HCID 86724463(R)-4-((1-cyclobutylethyl)amino)-3-(4-(trifluoromethyl)benzyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 61538Palladium, di-mu-chlorobis(eta3-2-propenyl)di-Catalyst

Conditions

Temperature
70 °C

Procedure

A vial containing 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (67.6 mg, 0.142 mmol) and allylpalladium(II) chloride dimer (26 mg, 0.071 mmol) in DMA (400 ul) was evacuated and refilled with Ar (3×). The resulting solution was warmed to 70° C. for 20 minutes. In a separate vial was added zinc cyanide (92 mg, 0.78 mmol), (R)-6-chloro-N-(1-cyclobutylethyl)-3-(4-(trifluoromethyl)benzyl)-3H-imidazo[4,5-c]pyridin-4-amine (290 mg, 0.71 mmol) and DMA (500 uL). The mixture was degassed with Ar for 15 minutes, and the catalyst solution was added to the mixture. The resulting mixture was stirred at 120° C. overnight. The mixture was cooled to room temperature and concentrated. The residue was dissolved in DCM purified by silica gel chromatography (0-100% ethyl acetate/hexanes, linear gradient) to give (R)-4-((1-cyclobutylethyl)amino)-3-(4-(trifluoromethyl)benzyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile. MS ESI calc'd for C21H20F3N5 [M+H]+ 400. found 400.

Workup

  1. customwas evacuated
  2. additionrefilled with Ar (3×)
  3. customThe mixture was degassed with Ar for 15 minutes
  4. additionthe catalyst solution was added to the mixture
  5. temperatureThe mixture was cooled to room temperature
  6. concentrationconcentrated
  7. dissolutionThe residue was dissolved in DCM
  8. custompurified by silica gel chromatography (0-100% ethyl acetate/hexanes, linear gradient)

Sources & evidence

ORD record
ord-138033f8ee2c457084e3eec78bd2a47b
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Linked notes

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