p-Toluenesulfonic acid → HCID 90041712, compound

HRID 530391Notes

Reaction equation

HRID 530391 reaction equation
C1(C)C=CC(S(O)(=O)=O)=CC=1.Cl[C:13]1[N:18]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:16]=[CH:15][N:14]=1.[CH3:23][S:24]([N:27]1[CH2:32][CH2:31][N:30]([C:33]2[CH:34]=[C:35]([NH2:45])[CH:36]=[C:37]([C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)[CH:38]=2)[CH2:29][CH2:28]1)(=[O:26])=[O:25]>O1CCOCC1.C(OCC)(=O)C>[CH3:23][S:24]([N:27]1[CH2:28][CH2:29][N:30]([C:33]2[CH:34]=[C:35]([NH:45][C:13]3[N:18]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:16]=[CH:15][N:14]=3)[CH:36]=[C:37]([C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)[CH:38]=2)[CH2:31][CH2:32]1)(=[O:25])=[O:26]

Participants

6

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 27739122-Chloro-4-(trifluoromethyl)pyrimidineHCID 90041415HCID 90041415, compound

Product 1

HCID 90041712HCID 90041712, compound

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

p-Toluenesulfonic acid (21.46 mg, 0.113 mmol) and 2-chloro-4-(trifluoromethyl)pyrimidine (22.5 mg, 0.123 mmol) were added to a solution of 5-[4-(methylsulfonyl)piperazin-1-yl]biphenyl-3-amine (34 mg, 0.103 mmol) in dioxane (1 mL) and the reaction mixture was stirred for 14 hours at 100° C., then allowed to cool to room temperature. The reaction mixture was diluted with ethyl acetate (30 mL), then washed with saturated aqueous NaHCO3 (30 mL) followed by brine (30 mL). The aqueous layers were extracted with ethyl acetate (30 mL), then the combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography (ethyl acetate/hexanes) provided N-{5-[4-(methylsulfonyl)piperazin-1-yl]biphenyl-3-yl}-4-(trifluoromethyl)pyrimidin-2-amine MS ESI calc'd. for C22H23F3N5O2S [M+H]+ 478, found 478. 1H NMR (400 MHz, Acetone): δ 9.18 (s, 1H); 8.82 (d, J=4.9 Hz, 1H); 7.71-7.66 (m, 4H); 7.47 (t, J=7.5 Hz, 2H); 7.37 (t, J=7.3 Hz, 1H); 7.23 (d, J=4.9 Hz, 1H); 7.02 (s, 1H); 3.43 (d, J=10.6 Hz, 8H); 2.91 (s, 3H).

Workup

  1. temperatureto cool to room temperature
  2. washwashed with saturated aqueous NaHCO3 (30 mL)
  3. extractionThe aqueous layers were extracted with ethyl acetate (30 mL)
  4. dry with materialthe combined organic layers were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-630559ab47e94e00b74a26797afeedab
Source dataset
uspto-grants-2016_05
Patent number
US09353066B2

Reaction notes

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