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

HRID 2176645Notes

Reaction equation

HRID 2176645 reaction equation
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

Participants

8

Reactant 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

Product 1

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

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-1769c88a47284e98989938b9923e3e27
Source dataset
uspto-grants-2015_06
Patent number
US09066954B2

Reaction notes

Loading…