p-Toluenesulfonic acid → 3-(5-(4-(Difluoromethoxy)phenyl)pyrimidin-2-ylamino)phenol

HRID 2067898Notes

Reaction equation

Cl[C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH:15]([F:17])[F:16])=[CH:10][CH:9]=2)=[CH:4][N:3]=1.[NH2:18][C:19]1[CH:20]=[C:21]([OH:25])[CH:22]=[CH:23][CH:24]=1.CC1C=CC(S(O)(=O)=O)=CC=1>O1CCOCC1.C([O-])([O-])=O.[Na+].[Na+]>[F:16][CH:15]([F:17])[O:14][C:11]1[CH:12]=[CH:13][C:8]([C:5]2[CH:4]=[N:3][C:2]([NH:18][C:19]3[CH:20]=[C:21]([OH:25])[CH:22]=[CH:23][CH:24]=3)=[N:7][CH:6]=2)=[CH:9][CH:10]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a mixture of 2-chloro-5-(4-(difluoromethoxy)phenyl)pyrimidine 30 (3.2 mmol) and 3-aminophenol (6.42 mmol) in 1,4-dioxane (5 mL) is added p-TSA (5.4 mmol). The reaction mixture is heated at 100° C. for 12 h. After this time, the reaction is diluted with a 2M solution of Na2CO3 and extracted with DCM (3×50 mL). The organic layer is washed with brine, dried over Na2SO4, and concentrated. Purification by short SiO2 chromatography using a DCM:EtOAc=7:3 as eluant affords (3-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)phenol 39. MS (m/z) (M+1)+: 330.1.

Workup

extractionextracted with DCM (3×50 mL)
washThe organic layer is washed with brine
dry with materialdried over Na2SO4
concentrationconcentrated
customPurification by short SiO2 chromatography

Sources & evidence

ORD record: ord-6a43c11cef454addb94ccd7738b48468
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08293757B2

Reaction notes

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