p-Toluenesulfonic acid monohydrate → HCID 90041420, compound

HRID 530381Notes

Reaction equation

HRID 530381 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.S(O)(C1C=CC(C)=CC=1)(=O)=O.O.[N:24]1([C:30]2[CH:31]=[C:32]([NH2:42])[CH:33]=[C:34]([C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[CH:35]=2)[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1>O1CCOCC1.C(OCC)(=O)C>[N:24]1([C:30]2[CH:31]=[C:32]([NH:42][C:2]3[N:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][N:3]=3)[CH:33]=[C:34]([C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[CH:35]=2)[CH2:25][CH2:26][O:27][CH2:28][CH2:29]1

Participants

6

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 27739122-Chloro-4-(trifluoromethyl)pyrimidineHCID 90042217HCID 90042217, compound

Product 1

HCID 90041420HCID 90041420, compound

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

2-Chloro-4-(trifluoromethyl)pyrimidine (23 μL, 0.19 mmol) and TsOH—H2O (29.9 mg, 0.157 mmol) were added to a solution of 5-(morpholin-4-yl)biphenyl-3-amine (40 mg, 0.157 mmol) in dioxane (1.5 mL) and then the reaction mixture was heated to 100° C. for 14 hours. The reaction mixture was diluted with ethyl acetate and washed with saturated NaHCO3 (aq) followed by brine. The aqueous layers were extracted with ethyl acetate, then the combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography (ethyl acetate/hexanes) provided N-[5-(morpholin-4-yl)biphenyl-3-yl]-4-(trifluoromethyl)pyrimidin-2-amine as a light yellow solid. MS ESI calc'd. for C21H20F3N4O [M+H]+ 401, found 401. 1H NMR (400 MHz, CDCl3): δ 8.66 (d, J=4.9 Hz, 1H); 7.61 (d, J=7.6 Hz, 2H); 7.56 (s, 1H); 7.50-7.34 (m, 4H); 7.23 (s, 1H); 7.05 (d, J=4.9 Hz, 1H); 6.88 (s, 1H); 3.92 (t, J=4.5 Hz, 4H); 3.29 (t, J=4.5 Hz, 4H).

Workup

  1. washwashed with saturated NaHCO3 (aq)
  2. extractionThe aqueous layers were extracted with ethyl acetate
  3. dry with materialthe combined organic extracts were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-96f844f1ed04454db3dde4056b291c10
Source dataset
uspto-grants-2016_05
Patent number
US09353066B2

Reaction notes

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