Water → 2-{5-[5-(4-Difluoromethoxy-phenyl)-pyrimidin-2-ylamino]-2-methyl-phenyl}-ethanol

HRID 2067911Notes

Reaction equation

HRID 2067911 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]=[CH:21][C:22]([CH3:28])=[C:23]([CH2:25][CH2:26][OH:27])[CH:24]=1.CC1C=CC(S(O)(=O)=O)=CC=1.O>O1CCOCC1>[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]=[CH:21][C:22]([CH3:28])=[C:23]([CH2:25][CH2:26][OH:27])[CH:24]=3)=[N:7][CH:6]=2)=[CH:9][CH:10]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6101p-Toluenesulfonic acidHCID 581719302-Chloro-5-(4-(difluoromethoxy)phenyl)pyrimidineHCID 585422572-(5-Amino-2-methylphenyl)ethanol

Product 1

HCID 687289402-{5-[5-(4-Difluoromethoxy-phenyl)-pyrimidin-2-ylamino]-2-methyl-phenyl}-ethanol

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A solution of 2-chloro-5-(4-difluoromethoxy-phenyl)-pyrimidine 30 (1.3 mmol), 2-(5-Amino-2-methyl-phenyl)-ethanol 50 (1.3 mmol) and p-TSA (0.24 g, 1.3 mmol) in dioxane (10 mL) is heated at 100° C. for 12 h then cooled to rt. The reaction mixture is slowly added to water (100 mL) with stirring. The resulting precipitate is collected by filtration, washed with water and air dried. The crude precipitate is purified by column chromatography on silica with hexanes:EtOAc=1:1 as eluant to yield 2-{5-[5-(4-difluoromethoxy-phenyl)-pyrimidin-2-ylamino]-2-methyl-phenyl}-ethanol 51a as solid. MS (m/z) (M+1)+: 372.3.

Workup

  1. filtrationThe resulting precipitate is collected by filtration
  2. washwashed with water and air
  3. customdried
  4. customThe crude precipitate is purified by column chromatography on silica with hexanes

Sources & evidence

ORD record
ord-ff8af9f02dc0467f90acbe319ff47f01
Source dataset
uspto-grants-2012_10
Patent number
US08293757B2

Reaction notes

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