Potassium Carbonate → 3-Isobutyl-2-{1-[4-(4-methoxy-benzenesulfonyl)-piperazin-1-yl]-ethyl}-3H-quinazolin-4-one

HRID 238212Notes

Reaction equation

HRID 238212 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([S:9]([N:12]2[CH2:17][CH2:16][N:15]([CH:18]([C:20]3[NH:29][C:28](=[O:30])[C:27]4[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=4)[N:21]=3)[CH3:19])[CH2:14][CH2:13]2)(=[O:11])=[O:10])=[CH:5][CH:4]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[CH2:26]([N:29]1[C:28](=[O:30])[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[N:21]=[C:20]1[CH:18]([N:15]1[CH2:14][CH2:13][N:12]([S:9]([C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)(=[O:10])=[O:11])[CH2:17][CH2:16]1)[CH3:19])[CH:27]([CH3:28])[CH3:22]

Participants

4

Reactant 2

HCID 11430Potassium CarbonateHCID 1358460552-{1-[4-(4-Methoxy-benzenesulfonyl)-piperazin-1-yl]-ethyl}-3H-quinazolin-4-one

Product 1

HCID 599934883-Isobutyl-2-{1-[4-(4-methoxy-benzenesulfonyl)-piperazin-1-yl]-ethyl}-3H-quinazolin-4-oneYield 72.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

In a flask containing of 2-{1-[4-(4-Methoxy-benzenesulfonyl)-piperazin-1-yl]-ethyl}-3H-quinazolin-4-one (50.0 mg, 0.12 mmol) in DMF was added I-Iodo-2-methylpropane (42.0 mg, 0.24 mmol), K2CO3 (80.0 mg, 0.6 mmol). The mixture was heated at 90° C. for 2 hours with stirring. After cooling down to room temperature, the excess K2CO3 was filtrated; the solution was treated with TFA (0.5 ml) and water (0.1 ml) with stirring at 90° C. for 2 hrs. Purification by HPLC (Gilson-215, 0.035% TFA in acetonitrile and 0.05% water as mobile phase) yielded 3-Isobutyl-2-{1-[4-(4-methoxy-benzenesulfonyl)-piperazin-1-yl]-ethyl}-3H-quinazolin-4-one (Yield 21.0 mg, 37.0%) that was dried under reduced pressure. 1H NMR (400 MHz, DMSO-6): δ 0.98 (d, 3H, J=6.82 Hz), 1.01 (d, 3H, J=6.82 Hz), 1.76 (d, 3H, J=6.82 Hz), 2.08-1.99 (m, 1H), 3.51-3.19 (m, 6H), 3.86-3.75 (m, 2H), 3.93 (s. 3H), 4.16-3.93 (m, 2H), 4.84 (q, 1H, J=12.88, 7.07 Hz), 7.03 (dd, 2H, J=6.82, 2.27 Hz), 7.57 (dt, 1H, J=8.08, 1.01 Hz), 7.67 (dd, 2H, J=6.82, 2.27 Hz), 7.71 (d, 1H, J=8.08, Hz), 7.82 (dt, 1H, 8.59, 1.52 Hz), 8.39 (dd, 1H, J=8.08, 1.52 Hz). MS m/z calc. 484.21, found (ESI); 485.3 (M+1)+. Retention time 2.83 minutes.

Workup

  1. temperatureAfter cooling down to room temperature
  2. filtrationthe excess K2CO3 was filtrated
  3. additionthe solution was treated with TFA (0.5 ml) and water (0.1 ml)
  4. stirringwith stirring at 90° C. for 2 hrs
  5. customPurification by HPLC (Gilson-215, 0.035% TFA in acetonitrile and 0.05% water as mobile phase)

Sources & evidence

ORD record
ord-66d97395244c4e109ce9736c5dd40729
Source dataset
uspto-grants-2014_02
Patent number
US08642609B2

Reaction notes

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