Water → Ethyl 3-(5-(2-(((2-chloro-4'-fluoro-3'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)amino)methyl)-4,5-difluorophenyl)picolinamido)propanoate

HRID 405209Notes

Reaction equation

HRID 405209 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][CH2:10][C:11]2[CH:16]=[C:15]([F:17])[C:14]([F:18])=[CH:13][C:12]=2[C:19]2[CH:20]=[CH:21][C:22]([C:25]([NH:27][CH2:28][CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31])=[O:26])=[N:23][CH:24]=2)[CH:5]=[CH:6][C:7]=1I.[F:35][C:36]1[CH:41]=[CH:40][C:39](B(O)O)=[CH:38][C:37]=1[C:45]([F:48])([F:47])[F:46].C([O-])([O-])=O.[K+].[K+].O>O1CCOCC1.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:1][C:2]1[CH:3]=[C:4]([NH:9][CH2:10][C:11]2[CH:16]=[C:15]([F:17])[C:14]([F:18])=[CH:13][C:12]=2[C:19]2[CH:20]=[CH:21][C:22]([C:25]([NH:27][CH2:28][CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31])=[O:26])=[N:23][CH:24]=2)[CH:5]=[CH:6][C:7]=1[C:39]1[CH:40]=[CH:41][C:36]([F:35])=[C:37]([C:45]([F:48])([F:47])[F:46])[CH:38]=1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 177500514-Fluoro-3-(trifluoromethyl)benzeneboronic acidHCID 71060063Ethyl 3-(5-(2-(((3-chloro-4-iodophenyl)amino)methyl)-4,5-difluorophenyl)picolinamido)propanoate

Product 1

HCID 86674273Ethyl 3-(5-(2-(((2-chloro-4'-fluoro-3'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)amino)methyl)-4,5-difluorophenyl)picolinamido)propanoate

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Procedure

Ethyl 3-(5-(2-(((3-chloro-4-iodophenyl)amino)methyl)-4,5-difluorophenyl)picolinamido)propanoate (123 mg, 0.21 mmol), (4-fluoro-3-(trifluoromethyl)phenyl)boronic acid (85 mg, 0.41 mmol), Pd(dppf)Cl2 (23 mg, 0.03 mmol), and K2CO3 (85 mg, 0.62 mmol) were dissolved in 1,4-dioxane (1 mL) and water (0.3 mL) and the resulting mixture was heated to 70° C. After 1 h the resulting mixture directly purified via column chromatography to yield the title compound.

Workup

  1. customAfter 1 h the resulting mixture directly purified via column chromatography

Sources & evidence

ORD record
ord-cc6b286c5465413fb72300590747c43f
Source dataset
uspto-grants-2014_06
Patent number
US08748624B2

Reaction notes

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