Picolinic acid → 3-(4-(3-(1,1-Difluoroethyl)phenoxy)phenyl)-5-methylpyridin-2-amine

HRID 1748043Notes

Reaction equation

N1C=CC=C[C:2]=1C(O)=O.[NH2:10][C:11]1[C:16]([C:17]2[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][CH:18]=2)=[CH:15][CH:14]=[CH:13][N:12]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[C:33]1[CH:38]=[CH:37][CH:36]=[C:35]([C:39]([F:42])([F:41])[CH3:40])[CH:34]=1>[Cu]I.CS(C)=O>[F:41][C:39]([C:35]1[CH:34]=[C:33]([CH:38]=[CH:37][CH:36]=1)[O:23][C:20]1[CH:21]=[CH:22][C:17]([C:16]2[C:11]([NH2:10])=[N:12][CH:13]=[C:14]([CH3:2])[CH:15]=2)=[CH:18][CH:19]=1)([F:42])[CH3:40]

Participants

Conditions

Temperature: 130 °C

Procedure

Copper(I) iodide (39.2 mg) was added to a mixture of picolinic acid (25.4 mg), 4-(2-aminopyridin-3-yl)phenol (206 mg), tripotassium phosphate (656 mg), 1-bromo-3-(1,1-difluoroethyl)benzene (239 mg) and DMSO (3 mL). The mixture was stirred at 130° C. under nitrogen for 10 hr. The insoluble solid was removed by filtration through silica gel/Celite pad (eluted with EtOAc). Silica-gel was added to the filtrate and the volatiles were removed in vacuo. The mixture supported on silica-gel was purified by column chromatography (NH-silica gel, eluted with EtOAc in hexane) to give the title compound (165 mg) as a yellow amorphous solid.

Workup

customThe insoluble solid was removed by filtration through silica gel/Celite pad (eluted with EtOAc)
additionSilica-gel was added to the filtrate
customthe volatiles were removed in vacuo
customwas purified by column chromatography (NH-silica gel, eluted with EtOAc in hexane)

Sources & evidence

ORD record: ord-14ddbb078973402bb89272201a5bfda0
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09150591B2

Reaction notes

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