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

HRID 405236Notes

Reaction equation

HRID 405236 reaction equation
Br[C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH:9]([NH:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)=[CH:14][CH:13]=1)[CH3:10].CC1(C)C(C)(C)OB([C:33]2[CH:34]=[CH:35][C:36]([C:39]([NH:41][CH2:42][CH2:43][C:44]([O:46][CH2:47][CH3:48])=[O:45])=[O:40])=[N:37][CH:38]=2)O1.C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C.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:8][C:6]1[CH:5]=[CH:4][C:3]([CH:9]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)=[CH:14][CH:13]=2)[CH3:10])=[C:2]([C:33]2[CH:34]=[CH:35][C:36]([C:39]([NH:41][CH2:42][CH2:43][C:44]([O:46][CH2:47][CH3:48])=[O:45])=[O:40])=[N:37][CH:38]=2)[CH:7]=1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 71059832Ethyl 3-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)picolinamido)propanoateHCID 71060075N-(1-(2-bromo-4-chlorophenyl)ethyl)-4'-fluoro-[1,1'-biphenyl]-4-amine

Product 1

HCID 71060007Ethyl 3-(5-(5-chloro-2-(1-((4'-fluoro-[1,1'-biphenyl]-4-yl)amino)ethyl)phenyl)picolinamido)propanoate

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolvent

Procedure

N-(1-(2-bromo-4-chlorophenyl)ethyl)-4′-fluoro-[1,1′-biphenyl]-4-amine (138 mg, 0.34 mmol), ethyl 3-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)picolinamido)propanoate (142 mg, 0.41 mmol), Pd(dppf)Cl2 (37 mg, 0.05 mmol), and K2CO3 (108 g, 0.78 mmol) were dissolved in wet DMF (3 mL) and water (4 mL) and heated to 90° C. After 16 h the resulting mixture was cooled to room temperature, filtered through CELITE and the filtrate was diluted with EtOAc, washed with water and sat. aqueous NaHCO3. The organic layer was dried (Na2SO4), concentrated and purified via column chromatography to yield the title compound.

Workup

  1. filtrationfiltered through CELITE
  2. additionthe filtrate was diluted with EtOAc
  3. washwashed with water and sat. aqueous NaHCO3
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. concentrationconcentrated
  6. custompurified via column chromatography

Sources & evidence

ORD record
ord-2acd82919088448981d50d61705f75cd
Source dataset
uspto-grants-2014_06
Patent number
US08748624B2

Reaction notes

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