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

HRID 408843ノート

反応式

HRID 408843 の反応式
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

参加物

6

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 3

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

反応条件

温度
120 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-21e1480eea344b61b17a80c67ffda983
出典データセット
uspto-grants-2014_06
特許番号
US08759361B2

反応ノート

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