Water → Tert-butyl 3-(5-(5-chloro-2-(((3'-(trifluoromethoxy)-[1,1'-biphenyl]-4-yl)amino)methyl)phenyl)picolinamido)propanoate

HRID 405215Notes

Reaction equation

HRID 405215 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:26][NH:27][C:28]2[CH:33]=[CH:32][C:31](Br)=[CH:30][CH:29]=2)=[C:6]([C:8]2[CH:9]=[CH:10][C:11]([C:14]([NH:16][CH2:17][CH2:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=[O:15])=[N:12][CH:13]=2)[CH:7]=1.[F:35][C:36]([F:48])([F:47])[O:37][C:38]1[CH:39]=[C:40](B(O)O)[CH:41]=[CH:42][CH:43]=1.C([O-])([O-])=O.[K+].[K+].O>O1CCOCC1.C(Cl)Cl.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]=[CH:4][C:5]([CH2:26][NH:27][C:28]2[CH:33]=[CH:32][C:31]([C:40]3[CH:41]=[CH:42][CH:43]=[C:38]([O:37][C:36]([F:35])([F:47])[F:48])[CH:39]=3)=[CH:30][CH:29]=2)=[C:6]([C:8]2[CH:9]=[CH:10][C:11]([C:14]([NH:16][CH2:17][CH2:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=[O:15])=[N:12][CH:13]=2)[CH:7]=1

Participants

8

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 27343853-(Trifluoromethoxy)phenylboronic Acid (contains varying amounts of Anhydride)HCID 71059988Tert-butyl 3-(5-(2-(((4-bromophenyl)amino)methyl)-5-chlorophenyl)picolinamido)propanoate

Product 1

HCID 71060116Tert-butyl 3-(5-(5-chloro-2-(((3'-(trifluoromethoxy)-[1,1'-biphenyl]-4-yl)amino)methyl)phenyl)picolinamido)propanoate

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

tert-Butyl 3-(5-(5-chloro-2-(((4-bromophenyl)amino)methyl)phenyl)picolinamido)propanoate (82 mg, 0.15 mmol), (3-(trifluoromethoxy)phenyl)boronic acid (41 mg, 0.20 mmol), Pd(dppf)Cl2 (18 mg, 0.02 mmol), and K2CO3 (55 mg, 0.40 mmol) were dissolved in 1,4-dioxane (1.5 mL) and water (0.5 mL) and heated to 120° C. in the microwave. After 1 h the resulting mixture was diluted with DCM, dried (Na2SO4), filtered through CELITE, and purified via column chromatography to yield the title compound.

Workup

  1. dry with materialdried (Na2SO4)
  2. filtrationfiltered through CELITE
  3. custompurified via column chromatography

Sources & evidence

ORD record
ord-f96f4fdae4324b858c9d4f83bd8f18ce
Source dataset
uspto-grants-2014_06
Patent number
US08748624B2

Reaction notes

Loading…