p-Toluenesulfonic acid monohydrate → HCID 90041903, compound

HRID 530384Notes

Reaction equation

HRID 530384 reaction equation
O.C1(C)C=CC(S(O)(=O)=O)=CC=1.Cl[C:14]1[N:19]=[C:18]([C:20]([F:23])([F:22])[F:21])[CH:17]=[CH:16][N:15]=1.[N:24]1([CH2:30][C:31]2[CH:32]=[C:33]([NH2:43])[CH:34]=[C:35]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[CH:36]=2)[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1>O1CCOCC1.C(OCC)(=O)C>[N:24]1([CH2:30][C:31]2[CH:32]=[C:33]([NH:43][C:14]3[N:19]=[C:18]([C:20]([F:23])([F:22])[F:21])[CH:17]=[CH:16][N:15]=3)[CH:34]=[C:35]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[CH:36]=2)[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1

Participants

6

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 27739122-Chloro-4-(trifluoromethyl)pyrimidineHCID 90041742HCID 90041742, compound

Product 1

HCID 90041903HCID 90041903, compound

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

p-Toluenesulfonic acid monohydrate (75 mg, 0.395 mmol) was added to a solution of 2-chloro-4-(trifluoromethyl)pyrimidine (36 mg, 0.198 mmol) and 5-(morpholin-4-ylmethyl)biphenyl-3-amine (53 mg, 0.198 mmol) in dioxane (1.98 mL) and heated to 80° C. for 14 hours, then allowed to cool to room temperature. The mixture was diluted with ethyl acetate (30 mL) and washed with saturate aqueous NaHCO3 (30 mL) and 1:1 water: brine (2×30 mL). The organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography (thyl acetate/hexanes) provided N-[5-(morpholin-4-ylmethyl)biphenyl-3-yl]-4-(trifluoromethyl)pyrimidin-2-amine. MS ESI calc'd. for C22H22F3N4O [M+H]+ 415, found 415. 1H NMR (400 MHz, CDCl3): δ 8.67 (d, J=4.9 Hz, 1H); 7.90 (s, 1H); 7.66 (d, J=7.7 Hz, 2H); 7.58 (s, 1H); 7.51-7.42 (m, 3H); 7.39 (t, J=7.4 Hz, 1H); 7.33 (s, 1H); 7.06 (d, J=4.9 Hz, 1H); 3.76 (t, J=4.5 Hz, 4H); 3.61 (s, 2H); 2.54 (t, J=4.2 Hz, 4H).

Workup

  1. temperatureto cool to room temperature
  2. washwashed with saturate aqueous NaHCO3 (30 mL) and 1:1 water
  3. dry with materialThe organic extracts were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel column chromatography (thyl acetate/hexanes)

Sources & evidence

ORD record
ord-31b356c01b694f0aa3855a2f291a26d2
Source dataset
uspto-grants-2016_05
Patent number
US09353066B2

Reaction notes

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