Potassium Phosphate, Tribasic → 6-((6-(3,5-Difluorophenyl)-8-fluoro-[1,2,4]triazolo[4,3-a]pyridin-3-yl)difluoromethyl)-3-methoxyquinoline

HRID 2176645노트

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HRID 2176645 반응식
Cl[C:2]1[CH:3]=[C:4]([F:26])[C:5]2[N:6]([C:8]([C:11]([F:25])([F:24])[C:12]3[CH:13]=[C:14]4[C:19](=[CH:20][CH:21]=3)[N:18]=[CH:17][C:16]([O:22][CH3:23])=[CH:15]4)=[N:9][N:10]=2)[CH:7]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[F:35][C:36]1[CH:37]=[C:38](B(O)O)[CH:39]=[C:40]([F:42])[CH:41]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CO.C(Cl)Cl>[F:35][C:36]1[CH:37]=[C:38]([C:2]2[CH:3]=[C:4]([F:26])[C:5]3[N:6]([C:8]([C:11]([F:24])([F:25])[C:12]4[CH:13]=[C:14]5[C:19](=[CH:20][CH:21]=4)[N:18]=[CH:17][C:16]([O:22][CH3:23])=[CH:15]5)=[N:9][N:10]=3)[CH:7]=2)[CH:39]=[C:40]([F:42])[CH:41]=1

참가 물질

8

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 2734338(3,5-Difluorophenyl)boronic acidHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 576912676-((6-Chloro-8-fluoro-[1,2,4]triazolo[4,3-a]pyridin-3-yl)difluoromethyl)-3-methoxyquinoline

생성물 1

HCID 576910536-((6-(3,5-Difluorophenyl)-8-fluoro-[1,2,4]triazolo[4,3-a]pyridin-3-yl)difluoromethyl)-3-methoxyquinoline수율 17.5%

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 887Methanol용매2회HCID 6344Dichloromethane용매

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온도
100 °C

실험 절차

A sealable microwave vial was charged with 6-((6-chloro-8-fluoro-[1,2,4]triazolo[4,3-a]pyridin-3-yl)difluoromethyl)-3-methoxyquinoline (342.05 mg, 903 μmol), palladium(II) acetate (30 mg, 135 μmol), potassium phosphate (575 mg, 2709 μmol), 3,5-difluorophenylboronic acid (285 mg, 1806 μmol), and X-Phos (129 mg, 271 μmol). The tube was sealed, and flushed with N2. Dioxane (9 mL), then H2O (1 mL) were added and the mixture was sparged with N2 for 10 min, then heated at 100° C. for 24 h. The mixture was cooled to rt and concentrated absorbed onto a 5 g loading cartridge for MPLC purification using a 98:2 CH2Cl2: MeOH to 90:10 CH2Cl2:MeOH gradient to give 6-((6-(3,5-difluorophenyl)-8-fluoro-[1,2,4]triazolo[4,3-a]pyridin-3-yl)difluoromethyl)-3-methoxyquinoline (72 mg, 17% yield). LRMS (ESI) m/z calcd for C23H14F5N4O (M+H) 457.1. found 457.0.

후처리

  1. customThe tube was sealed
  2. customflushed with N2
  3. additionDioxane (9 mL), then H2O (1 mL) were added
  4. customthe mixture was sparged with N2 for 10 min
  5. temperatureThe mixture was cooled to rt
  6. concentrationconcentrated
  7. customabsorbed onto a 5 g loading cartridge for MPLC purification

출처 및 근거

ORD 기록
ord-1769c88a47284e98989938b9923e3e27
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09066954B2

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