2,2,2-Trifluoroethyl trifluoromethanesulfonate → 2-(4-(4-(2,2,2-Trifluoroethyl)piperazin-1-yl)phenyl)quinazolin-4(3H)-one

HRID 591634Notes

Reaction equation

HRID 591634 reaction equation
[N:1]1([C:7]2[CH:12]=[CH:11][C:10]([C:13]3[NH:22][C:21](=[O:23])[C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[N:14]=3)=[CH:9][CH:8]=2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.CCN(C(C)C)C(C)C.FC(F)(F)S(O[CH2:39][C:40]([F:43])([F:42])[F:41])(=O)=O>C1COCC1>[F:41][C:40]([F:43])([F:42])[CH2:39][N:4]1[CH2:5][CH2:6][N:1]([C:7]2[CH:8]=[CH:9][C:10]([C:13]3[NH:22][C:21](=[O:23])[C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[N:14]=3)=[CH:11][CH:12]=2)[CH2:2][CH2:3]1

Participants

5

Reactant 3

HCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonateHCID 81531DiisopropylethylamineHCID 1363480052-(4-(piperazin-1-yl)phenyl)quinazolin-4(3H)-one

Product 1

HCID 1359391102-(4-(4-(2,2,2-Trifluoroethyl)piperazin-1-yl)phenyl)quinazolin-4(3H)-oneYield 94%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 2-(4-(piperazin-1-yl)phenyl)quinazolin-4(3H)-one (0.325 g, 1.06 mmol) in THF (50 mL) was added Hünig's base (0.192 g, 1.48 mmol), followed by 2,2,2-trifluoroethyl trifluoromethanesulfonate (0.295 g, 1.3 mmol). The reaction mixture was heated at reflux for 15 hours, concentrated, and purified by flash chromatography on silica gel, eluting with 100% CH2Cl2 to 100% ethyl acetate, to afford the title compound as an off-white solid (0.385 g, 94%). 1H NMR (300 MHz, DMSO-d6): δ 12.27 (br s, 1H), 8.10-8.14 (m, 3H), 7.76-7.82 (m, 1H), 7.67 (d, J=7.8 Hz, 1H), 7.42-7.47 (m, 1H), 7.05 (d, J=9.1 Hz, 2H), 3.21-3.34 (m, 6H), 2.73-2.78 (m, 4H). APCI MS m/z 389 [M+H]+.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 15 hours
  3. concentrationconcentrated
  4. custompurified by flash chromatography on silica gel
  5. washeluting with 100% CH2Cl2 to 100% ethyl acetate

Sources & evidence

ORD record
ord-83423579c79943ffa1498ebb87cb6911
Source dataset
uspto-grants-2016_01
Patent number
US09238640B2

Reaction notes

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