p-Toluenesulfonic acid monohydrate → HCID 86658233, compound

HRID 1039871Notes

Reaction equation

HRID 1039871 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][N:3]=1.[Br:12][C:13]1[CH:14]=[C:15]([CH:17]=[C:18]([C:20]([F:23])([F:22])[F:21])[CH:19]=1)[NH2:16].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>O1CCOCC1.C(OCC)(=O)C.C(OCC)C>[Br:12][C:13]1[CH:14]=[C:15]([NH:16][C:2]2[N:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][N:3]=2)[CH:17]=[C:18]([C:20]([F:22])([F:23])[F:21])[CH:19]=1

Participants

7

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 27358803-Bromo-5-(trifluoromethyl)anilineHCID 27739122-Chloro-4-(trifluoromethyl)pyrimidine

Product 1

HCID 86658233HCID 86658233, compoundYield 100%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 2-chloro-4-trifluoromethylpyrimidine (1.224 g, 6.71 mmol) and 3-bromo-5-(trifluoromethyl)aniline (1.4 g, 5.83 mmol) in dioxane (20 ml) was added p-toluene-sulfonic acid monohydrate (1.220 g, 6.42 mmol). An immediate white suspension formed. The tube was sealed and the slurry was stirred and heated at 100° C. for 24 h. The now clear solution was diluted with ethyl acetate and diethyl ether and washed with saturated NaHCO3 (aq.). The organic fraction was dried over MgSO4 and concentrated in vacuo. Product was further purified by column chromatography on silica gel, eluting with ethyl acetate/hexane with a gradient 0-30% to afford N-[3-bromo-5-(trifluoromethyl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (2.252 g, 87%) as a light beige solid. MS APCI: [M+H]+ m/z 386.0. 1H NMR (400 MHz, CDCl3): δ 8.75 (d, J=4.9 Hz, 1H); 8.09 (s, 1H); 7.94 (s, 1H); 7.52-7.43 (m, 2H); 7.17 (d, J=4.9 Hz, 1H). rhSYK activity=+.

Workup

  1. customAn immediate white suspension formed
  2. customThe tube was sealed
  3. washwashed with saturated NaHCO3 (aq.)
  4. dry with materialThe organic fraction was dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customProduct was further purified by column chromatography on silica gel
  7. washeluting with ethyl acetate/hexane with a gradient 0-30%

Sources & evidence

ORD record
ord-8f02650903ea4ec2a08cf599be209164
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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