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

HRID 405153노트

반응식

HRID 405153 반응식
[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

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

실험 절차

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.

후처리

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

출처 및 근거

ORD 기록
ord-c7f664f2f25947028353947e345fab61
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08748624B2

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