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

HRID 2176645ノート

反応式

HRID 2176645 の反応式
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

参加物

8

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 887Methanol溶媒2 回HCID 6344Dichloromethane溶媒

反応条件

温度
100 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-1769c88a47284e98989938b9923e3e27
出典データセット
uspto-grants-2015_06
特許番号
US09066954B2

反応ノート

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