Dichloromethane → 2-(4-(7-(4-Chlorophenyl)-2-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-3-oxo-2,3-dihydro-[1,2,4]triazolo[4,3-a]pyridin-8-yl)phenyl)acetonitrile

HRID 2101313노트

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HRID 2101313 반응식
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.CC1(C)C(C)(C)OB([C:39]2[CH:44]=[CH:43][C:42]([CH2:45][C:46]#[N:47])=[CH:41][CH:40]=2)O1.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:39]2[CH:44]=[CH:43][C:42]([CH2:45][C:46]#[N:47])=[CH:41][CH:40]=2)=[CH:9][CH:10]=1

참가 물질

8

반응물 4

HCID 6344DichloromethaneHCID 62657Potassium Phosphate, TribasicHCID 38429222-(4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetonitrileHCID 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

생성물 1

HCID 160052022-(4-(7-(4-Chlorophenyl)-2-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-3-oxo-2,3-dihydro-[1,2,4]triazolo[4,3-a]pyridin-8-yl)phenyl)acetonitrile

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

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온도
90 °C

실험 절차

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 (60 mg, 0.12 mmol) in THF (2 mL) at room temperature under argon was added 2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetonitrile (87.9 mg, 0.36 mmol), Pd(dppf)Cl2.CH2Cl2 (9.8 mg, 0.011 mmol), and K3PO4 (77 mg, 0.36 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 48 h, and then cooled to room temperature. Analysis by HPLC/MS indicated that starting material was still present 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, 38 mg, 59%. HPLC/MS: retention time=3.94 min, [M+H]+=534. 1H NMR (CDCl3): δ 7.84 (d, J=7.8 Hz, 1H), 7.66 (d, J=7.9 Hz, 1H), 7.49 (d, J=7.9 Hz, 1H), 7.25 (m, 6H), 7.05 (d, J=8.4 Hz, 2H), 6.66 (d, J=7.1 Hz, 1H), 5.24 (s, 2H), 3.75 (s, 2H), 2.74 (s, 3H).

후처리

  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

출처 및 근거

ORD 기록
ord-08e24022d2fa4350a56a3211c3e54536
출처 데이터셋
uspto-grants-2009_08
특허 번호
US07572808B2

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