Dimethylformamide → 4-[9-Methyl-6-oxo-2-(2,3,4-trifluorophenoxy)-6,9-dihydro-1H-purin-1-yl]benzonitrile

HRID 1674715Notes

Reaction equation

HRID 1674715 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16](=[O:17])[C:15]3[N:14]=[CH:13][N:12]([CH3:18])[C:11]=3[N:10]=[C:9]2[O:19][C:20]2[CH:25]=[CH:24][C:23]([F:26])=[C:22]([F:27])[C:21]=2[F:28])=[CH:4][CH:3]=1.[CH3:29][N:30](C=O)C>[C-]#N.[C-]#N.[Zn+2].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].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].O>[CH3:18][N:12]1[CH:13]=[N:14][C:15]2[C:16](=[O:17])[N:8]([C:5]3[CH:6]=[CH:7][C:2]([C:29]#[N:30])=[CH:3][CH:4]=3)[C:9]([O:19][C:20]3[CH:25]=[CH:24][C:23]([F:26])=[C:22]([F:27])[C:21]=3[F:28])=[N:10][C:11]1=2

Participants

7

Reactant 2

HCID 6228DimethylformamideHCID 247440321-(4-Bromophenyl)-9-methyl-2-(2,3,4-trifluorophenoxy)-1,9-dihydro-6H-purin-6-one

Product 1

HCID 576141454-[9-Methyl-6-oxo-2-(2,3,4-trifluorophenoxy)-6,9-dihydro-1H-purin-1-yl]benzonitrile

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

1-(4-Bromophenyl)-9-methyl-2-(2,3,4-trifluorophenoxy)-1,9-dihydro-6H-purin-6-one (68 mg, 0.1507 mmol), Zn(CN)2 (10.6 mg, 0.0904 mmol), Pd2(dba)3 (4.1 mg, 0.0045 mmol) and 1,1′-bis(diphenylphosphino)ferrocene (5.0 mg, 0.0090 mmol) are added to DMF (1.2 mL) and H2O (0.012 mL). The mixture is purged with N2 for 3 min and then heated at 120° C. for 18 h. The mixture is passed through celite. Water (30 mL) is added and the resulting mixture is extracted with CH2Cl2 (50 mL×4). After drying the CH2Cl2 over MgSO4, the solvent is removed in vacuo. The crude product is purified by column chromatography (MeOH:CH2Cl2=2:98) to afford the title compound as a brown solid. 1H NMR (400 MHz, CDCl3) 7.86 (2H, d, J 8), 7.65 (1H, s), 7.53 (2 h, d, J 8), 6.95 (2H, m), 3.59 (3H, s). MS (M+1): 398.03; RT=1.22 min.

Workup

  1. customThe mixture is purged with N2 for 3 min
  2. additionWater (30 mL) is added
  3. extractionthe resulting mixture is extracted with CH2Cl2 (50 mL×4)
  4. dry with materialAfter drying the CH2Cl2 over MgSO4
  5. customthe solvent is removed in vacuo
  6. customThe crude product is purified by column chromatography (MeOH:CH2Cl2=2:98)

Sources & evidence

ORD record
ord-8ea6785b39ab4e8594fda3ef475be87d
Source dataset
uspto-grants-2011_08
Patent number
US08003656B2

Reaction notes

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