Dichloromethane → 7-(4-chlorophenyl)-8-(2-methoxypyrimidin-5-yl)-2-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

HRID 2101310

反応式

HRID 2101310 の反応式
Br[C:2]1[C:3]2[N:4]([C:15](=[O:30])[N:16]([CH2:18][C:19]3[C:20]([CH3:29])=[N:21][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:23][CH:24]=3)[N:17]=2)[CH:5]=[CH:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=1.[CH3:31][O:32][C:33]1[N:38]=[C:37](B(O)O)[CH:36]=[CH:35][N:34]=1.C(Cl)Cl.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1COCC1.CCOC(C)=O.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]>[Cl:14][C:11]1[CH:12]=[CH:13][C:8]([C:7]2[CH:6]=[CH:5][N:4]3[C:15](=[O:30])[N:16]([CH2:18][C:19]4[C:20]([CH3:29])=[N:21][C:22]([C:25]([F:27])([F:28])[F:26])=[CH:23][CH:24]=4)[N:17]=[C:3]3[C:2]=2[C:36]2[CH:35]=[N:34][C:33]([O:32][CH3:31])=[N:38][CH:37]=2)=[CH:9][CH:10]=1

参加物

8

反応物 4

HCID 6344DichloromethaneHCID 62657Potassium Phosphate, TribasicHCID 45785507(2-Methoxypyrimidin-4-YL)boronic acidHCID 577994058-bromo-7-(4-chlorophenyl)-2-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

生成物 1

HCID 577993597-(4-chlorophenyl)-8-(2-methoxypyrimidin-5-yl)-2-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

試薬・触媒・溶媒 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
90 °C

実験手順

To a stirring solution of 8-bromo-7-(4-chlorophenyl)-2-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (125 mg, 0.25 mmol) in THF (4 mL) at room temperature under argon was added 2-methoxy-4-pyrimidinylboronic acid (116.0 mg, 0.75 mmol), Pd(dppf)Cl2.CH2Cl2 (23 mg, 0.025 mmol), and K3PO4 (160 mg, 0.75 mmol). The resulting suspension was purged of oxygen by bubbling with argon for 15 min, sealed in a vial under argon, heated at 90° C. for 12 h, and then cooled to room temperature. Analysis by HPLC/MS indicated that starting material was absent and one major new product had formed. The reaction mixture was diluted with EtOAc and washed once with brine. The organic layer was dried (MgSO4), filtered, and concentrated under reduced pressure. The crude product was purified by automated silica gel chromatography (eluted with EtOAc/hexanes). Pooling of the desired fractions, washing with saturated aq. NaHCO3 solution to eliminate any possible boronic acid contaminant, drying the organic phase (MgSO4), filtering and evaporation provided the title compound as a yellow solid, 147 mg, 80%. HPLC/MS: retention time=3.89 min, [M+H]+=527. 1H NMR (CDCl3): δ 8.43 (s, 2H), 7.86 (d, J=7.2 Hz, 1H), 7.72 (d, J=7.7 Hz, 1H), 7.50 (d, J=7.7 Hz, 2H), 7.13 (d, J=7.7 Hz, 2H), 6.66 (d, J=7.7 Hz, 1H), 5.25 (s, 2H), 4.01 (s, 3H), 2.76 (s, 3H).

後処理

  1. customThe resulting suspension was purged of oxygen
  2. customby bubbling with argon for 15 min
  3. customsealed in a vial under argon
  4. temperaturecooled to room temperature
  5. customone major new product had formed
  6. washwashed once with brine
  7. dry with materialThe organic layer was dried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe crude product was purified by automated silica gel chromatography (eluted with EtOAc/hexanes)
  11. washPooling of the desired fractions, washing with saturated aq. NaHCO3 solution
  12. dry with materialdrying the organic phase (MgSO4)
  13. filtrationfiltering
  14. customevaporation

出典と根拠

ORDレコード
ord-c418d1de9cd9441f93df047fae569a59
出典データセット
uspto-grants-2009_08
特許番号
US07572808B2

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