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

HRID 408843노트

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HRID 408843 반응식
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

참가 물질

6

반응물 2

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

생성물 1

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

시약·촉매·용매 3

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

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온도
120 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-21e1480eea344b61b17a80c67ffda983
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08759361B2

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