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

HRID 2067903Notes

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]([CH2:25][OH:26])[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]([CH2:25][OH:26])[CH:22]=[CH:23][CH:24]=3)=[N:7][CH:6]=2)=[CH:9][CH:10]=1

Participants

Conditions

Temperature: 105 °C

Procedure

To a mixture of 2-chloro-5-(4-(difluoromethoxy)phenyl)pyrimidine 30 (0.40 mmol) and (3-aminophenyl)methanol (0.40 mmol) in 1,4-dioxane (0.5 mL) is added p-TSA (0.4 mmol). The reaction mixture is heated at 105° C. for 2 days. After this time, the reaction mixture is diluted with a solution of 2M Na2CO3 (30 mL) and extracted with DCM (3×30 mL). The organic layer is washed with brine, dried over Na2SO4 and concentrated. Purification by short silica gel chromatography using a hexane:EtOAc=1:2 affords (3-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)phenyl)methanol 36. 1H NMR (400 MHz, d4-MeOH) δ 8.56 (s, 2H), 7.65 (m, 1H), 7.48-7.52 (m, 1H), 7.42-7.46 (m, 2H), 7.29 (t, J=8 Hz, 1H), 7.15-7.18 (m, 3H), 6.99-7.03 (m, 1H), 6.49 (t, J=73.6 Hz, 1H), 4.67 (s, 2H). MS (m/z) (M+1)+ 344.1.

Workup

extractionextracted with DCM (3×30 mL)
washThe organic layer is washed with brine
dry with materialdried over Na2SO4
concentrationconcentrated
customPurification by short silica gel chromatography

Sources & evidence

ORD record: ord-aeca2f6951a441dbb3cce054ea58a3ad
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08293757B2

Reaction notes

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