Dimethylformamide → 5-(9-Methyl-6-oxo-2-(3,4,5-trifluorophenoxy)-6H-purin-1(9H)-yl)picolinonitrile

HRID 408843Notes

Reaction equation

HRID 408843 reaction equation
Cl[C:2]1[N: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]=[C:24]([F:26])[C:23]([F:27])=[C:22]([F:28])[CH:21]=2)=[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].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.[Fe+2]>[CH3:18][N:12]1[CH:13]=[N:14][C:15]2[C:16](=[O:17])[N:8]([C:5]3[CH:4]=[CH:3][C:2]([C:29]#[N:30])=[N:7][CH:6]=3)[C:9]([O:19][C:20]3[CH:25]=[C:24]([F:26])[C:23]([F:27])=[C:22]([F:28])[CH:21]=3)=[N:10][C:11]1=2

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 249578951-(6-chloropyridin-3-yl)-9-methyl-2-(3,4,5-trifluorophenoxy)-1H-purin-6(9H)-one

Product 1

HCID 249597355-(9-Methyl-6-oxo-2-(3,4,5-trifluorophenoxy)-6H-purin-1(9H)-yl)picolinonitrile

Reagents, catalysts & solvents 3

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

Conditions

Temperature
120 °C

Procedure

1-(6-chloropyridin-3-yl)-9-methyl-2-(3,4,5-trifluorophenoxy)-1,9-dihydro-6H-purin-6-one (0.3 g, 0.73 mmol), Zn(CN)2 (0.43 mg, 3.65 mmol), Pd2(dba)3 (0.07 g, 0.073 mmol) and DPPF (0.04 g, 0.073 mmol) are added to DMF (3 mL). The mixture is purged with N2 for 3 min and then heated at 120° C. for 18 h. Water (20 mL) is added and the resulting mixture is extracted with DCM (2×20 mL). The organic layer is passed through celite and Na2SO4 and the solvent is removed in vacuo. The crude product is purified by column chromatography on silica gel (MeOH:CH2Cl2=2:98) to afford the title compound as a white solid. 1H NMR (300 MHz, CDCl3) δ 8.71 (s, 1H), 7.90 (s, 2H), 7.68 (s, 1H), 7.25 (s, 2H), 6.85-6.89 (m, 2H), 3.65 (s, 3H, s). MS (M+1): 399.07; RT=1.41 min. The IC50 determined as described in Example 6 is 100 nanomolar or less.

Workup

  1. customThe mixture is purged with N2 for 3 min
  2. additionWater (20 mL) is added
  3. extractionthe resulting mixture is extracted with DCM (2×20 mL)
  4. customthe solvent is removed in vacuo
  5. customThe crude product is purified by column chromatography on silica gel (MeOH:CH2Cl2=2:98)

Sources & evidence

ORD record
ord-21e1480eea344b61b17a80c67ffda983
Source dataset
uspto-grants-2014_06
Patent number
US08759361B2

Reaction notes

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