Potassium Carbonate → 5-(5-(3-Amino-4-fluoro-1-(2-(trifluoromethyl)pyridin-4-yl)-1H-isoindol-1-yl)-2-fluorophenyl)nicotinonitrile trifluoroacetate

HRID 1662246Notes

Reaction equation

HRID 1662246 reaction equation
[C:1]([C:3]1[CH:4]=[N:5][CH:6]=[C:7](B2OC(C)(C)C(C)(C)O2)[CH:8]=1)#[N:2].Br[C:19]1[CH:20]=[C:21]([C:26]2([C:37]3[CH:42]=[CH:41][N:40]=[C:39]([C:43]([F:46])([F:45])[F:44])[CH:38]=3)[C:34]3[C:29](=[C:30]([F:35])[CH:31]=[CH:32][CH:33]=3)[C:28]([NH2:36])=[N:27]2)[CH:22]=[CH:23][C:24]=1[F:25].[C:47](=[O:50])([O-])[O-:48].[K+].[K+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].CN(C=O)C>[F:44][C:43]([F:46])([F:45])[C:47]([OH:48])=[O:50].[NH2:36][C:28]1[C:29]2[C:34](=[CH:33][CH:32]=[CH:31][C:30]=2[F:35])[C:26]([C:21]2[CH:20]=[CH:19][C:24]([F:25])=[C:23]([C:7]3[CH:6]=[N:5][CH:4]=[C:3]([CH:8]=3)[C:1]#[N:2])[CH:22]=2)([C:37]2[CH:42]=[CH:41][N:40]=[C:39]([C:43]([F:46])([F:45])[F:44])[CH:38]=2)[N:27]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 164142165-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)nicotinonitrile4×HCID 585794921-(3-Bromo-4-fluorophenyl)-4-fluoro-1-(2-(trifluoromethyl)pyridin-4-yl)-1H-isoindol-3-amine

Product 1

HCID 866418175-(5-(3-Amino-4-fluoro-1-(2-(trifluoromethyl)pyridin-4-yl)-1H-isoindol-1-yl)-2-fluorophenyl)nicotinonitrile trifluoroacetateYield 15.1%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst4×HCID 6228DimethylformamideSolvent

Procedure

3-Cyanopyridine-5-boronic acid pinacol ester (85 mg, 0.37 mmol), 1-(3-bromo-4-fluorophenyl)-4-fluoro-1-(2-(trifluoromethyl)pyridin-4-yl)-1H-isoindol-3-amine (115.5 mg, 0.25 mmol), [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) chloride (10.07 mg, 0.01 mmol), 2 M aqueous potassium carbonate (0.370 mL, 0.74 mmol) and DMF (2.00 mL) were put in a microwave vial and irradiated in a microwave oven at 110° C. for 20 min. Additional 3-cyanopyridine-5-boronic acid pinacol ester (36.9 mg, 0.16 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) chloride (10.07 mg, 0.01 mmol) were added and the resulting mixture was irradiated at 110° C. for 20 min. Additional 3-cyanopyridine-5-boronic acid pinacol ester (36.9 mg, 0.16 mmol) and [1,1′-bis (diphenylphosphino)ferrocene]palladium(II) chloride (10.07 mg, 0.01 mmol) were added and the resulting mixture was irradiated at 110° C. for 30 min. Additional 3-cyanopyridine-5-boronic acid pinacol ester (36.9 mg, 0.16 mmol) and [1,1′-bis (diphenylphosphino)ferrocene]palladium(II) chloride (10.07 mg, 0.01 mmol) were added and the resulting mixture was irradiated for 30 min. The resulting product mixture was filtered and purified by preparative-HPLC to give the title compound 11.4 mg, (7.6% yield).

Workup

  1. customirradiated in a microwave oven at 110° C. for 20 min
  2. customthe resulting mixture was irradiated at 110° C. for 20 min
  3. customthe resulting mixture was irradiated at 110° C. for 30 min
  4. customthe resulting mixture was irradiated for 30 min
  5. filtrationThe resulting product mixture was filtered
  6. custompurified by preparative-HPLC

Sources & evidence

ORD record
ord-5dad8bd977404d2790d27b603c1e22cf
Source dataset
uspto-grants-2011_10
Patent number
US08030500B2

Reaction notes

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