Potassium Phosphate, Tribasic → 4-[3-(6-Amino-pyridin-3-ylethynyl)-2-ethyl-pyridin-4-yl]-2-fluoro-benzoic acid methyl ester

HRID 1529216Notes

Reaction equation

Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([CH2:8][CH3:9])[C:3]=1[C:10]#[C:11][C:12]1[CH:13]=[CH:14][C:15]([NH2:18])=[N:16][CH:17]=1.[F:19][C:20]1[CH:21]=[C:22](B(O)O)[CH:23]=[CH:24][C:25]=1[C:26]([O:28][CH3:29])=[O:27].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[Li+].[Cl-].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>COCCOC.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:29][O:28][C:26](=[O:27])[C:25]1[CH:24]=[CH:23][C:22]([C:2]2[CH:7]=[CH:6][N:5]=[C:4]([CH2:8][CH3:9])[C:3]=2[C:10]#[C:11][C:12]2[CH:17]=[N:16][C:15]([NH2:18])=[CH:14][CH:13]=2)=[CH:21][C:20]=1[F:19]

Participants

Conditions

Temperature: 95 °C

Procedure

The title compound is synthesized according to general procedure GP3 starting from 3.2 g (12.3 mmol) 5-(4-Chloro-2-ethyl-pyridin-3-ylethynyl)-pyridin-2-ylamine (A-30) using 3.6 g (18.4 mmol) 3-Fluoro-4-methoxycarbonylphenyl boronic acid, 561 mg (0.61 mmol) Pd2(dba)3, 877 mg (1.84 mmol) X-Phos, 519 mg (12.3 mmol) LiCl and 3.39 g (14.7 mmol) K3PO4 in a mixture of 60 mL 1,2-dimethoxyethane and 10 mL water. The reaction mixture is stirred for 16 h at 95° C. After completion of the reaction, the mixture is poured into water and the formed precipitate is collected by filtration. The product is purified by chromatography on silica gel using an DCM/MeOH-mixture (3% MeOH, flow 55 mL/min). Yield: 2.46 g (53%).

Workup

customAfter completion of the reaction
filtrationthe formed precipitate is collected by filtration
customThe product is purified by chromatography on silica gel using an DCM/MeOH-mixture (3% MeOH, flow 55 mL/min)

Sources & evidence

ORD record: ord-c5567166cb384475b823f68fc3780a42
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09090564B2

Reaction notes

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