Water → 3-(5-(2-(((2-Chloro-4'-fluoro-3'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)amino)methyl)-5-(trifluoromethyl)phenyl)picolinamido)propanoic acid

HRID 405153Notes

Reaction equation

HRID 405153 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][C:12]=2[C:21]2[CH:22]=[CH:23][C:24]([C:27]([NH:29][CH2:30][CH2:31][C:32]([O:34]CC)=[O:33])=[O:28])=[N:25][CH:26]=2)[CH:5]=[CH:6][C:7]=1I.[F:37][C:38]1[CH:43]=[CH:42][C:41](B(O)O)=[CH:40][C:39]=1[C:47]([F:50])([F:49])[F:48].C([O-])([O-])=O.[K+].[K+].O>O1CCOCC1.CCOC(C)=O.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]=[CH:15][C:14]([C:17]([F:20])([F:18])[F:19])=[CH:13][C:12]=2[C:21]2[CH:22]=[CH:23][C:24]([C:27]([NH:29][CH2:30][CH2:31][C:32]([OH:34])=[O:33])=[O:28])=[N:25][CH:26]=2)[CH:5]=[CH:6][C:7]=1[C:41]1[CH:42]=[CH:43][C:38]([F:37])=[C:39]([C:47]([F:50])([F:49])[F:48])[CH:40]=1

Participants

8

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 177500514-Fluoro-3-(trifluoromethyl)benzeneboronic acidHCID 71059989Ethyl 3-(5-(2-(((3-chloro-4-iodophenyl)amino)methyl)-5-(trifluoromethyl)phenyl)picolinamido)propanoate

Product 1

HCID 866742513-(5-(2-(((2-Chloro-4'-fluoro-3'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)amino)methyl)-5-(trifluoromethyl)phenyl)picolinamido)propanoic acid

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

Ethyl 3-(5-(2-(((3-chloro-4-iodophenyl)amino)methyl)-5-(trifluoromethyl)phenyl)picolinamido)propanoate (300 mg, 0.48 mmol), (4-fluoro-3-(trifluoromethyl)phenyl)boronic acid (138 mg, 0.67 mmol), Pd(dppf)Cl2 (39 mg, 0.05 mmol), and K2CO3 (131 mg, 0.95 mmol) were dissolved in 1,4-dioxane (1.6 mL) and water (0.4 mL) and the resulting mixture was heated to 80° C. After 16 h the resulting mixture was cooled to room temperature, diluted with EtOAc, washed with water and brine, dried (Na2SO4), and dry packed onto silica gel. Column chromatography yielded the title compound.

Workup

  1. washwashed with water and brine
  2. dry with materialdried (Na2SO4)
  3. customdry

Sources & evidence

ORD record
ord-c7f664f2f25947028353947e345fab61
Source dataset
uspto-grants-2014_06
Patent number
US08748624B2

Reaction notes

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