1-((4-Methoxyphenyl)sulfonyl)piperazine → 2-{1-[4-(4-Methoxy-benzenesulfonyl)-piperazin-1-yl]-ethyl}-3-methyl-4-oxo-3,4-dihydro-quinazoline-6-carbonitrile

HRID 238205Notes

Reaction equation

HRID 238205 reaction equation
Br[CH:2]([C:4]1[N:13]([CH3:14])[C:12](=[O:15])[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:16]#[N:17])[CH:10]=2)[N:5]=1)[CH3:3].[CH3:18][O:19][C:20]1[CH:25]=[CH:24][C:23]([S:26]([N:29]2[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]2)(=[O:28])=[O:27])=[CH:22][CH:21]=1>C(#N)C>[CH3:18][O:19][C:20]1[CH:25]=[CH:24][C:23]([S:26]([N:29]2[CH2:34][CH2:33][N:32]([CH:2]([C:4]3[N:13]([CH3:14])[C:12](=[O:15])[C:11]4[C:6](=[CH:7][CH:8]=[C:9]([C:16]#[N:17])[CH:10]=4)[N:5]=3)[CH3:3])[CH2:31][CH2:30]2)(=[O:28])=[O:27])=[CH:22][CH:21]=1

Participants

4

Reactant 2

HCID 7975601-((4-Methoxyphenyl)sulfonyl)piperazineHCID 599934582-(1-Bromo-ethyl)-3-methyl-4-oxo-3,4-dihydro-quinazoline-6-carbonitrile

Product 1

HCID 599931892-{1-[4-(4-Methoxy-benzenesulfonyl)-piperazin-1-yl]-ethyl}-3-methyl-4-oxo-3,4-dihydro-quinazoline-6-carbonitrileYield 8.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

In a test tube containing of 2-(1-bromo-ethyl)-3-methyl-4-oxo-3,4-dihydro-quinazoline-6-carbonitrile (40.0 mg, 0.14 mmol) in acetonitrile (2 ml) was added KI (34.0 mg, 0.21 mmol), and (1-(4-Methoxy-benzenesulfonyl)-piperazine (46.4 mg, 0.21 mmol). The reaction was heated for 18 hours. The solution was concentrated under reduced pressure. The residue was partitioned between water (2 ml) and dichloromethane (5 ml). The organic layer was dried over magnesium sulfate, filtered and concentrated under reduced pressure. The solvent was removed under vacuum. The resulting residue was dissolvent in DMSO (2 ml) and purified by HPLC (Gilson-215, 0.035% TFA in acetonitrile and 0.05% water as mobile phase). The product was collected and dried under reduced pressure to give the 2-{1-[4-(4-Methoxy-benzenesulfonyl)-piperazin-1-yl]-ethyl}-3-methyl-4-oxo-3,4-dihydro-quinazoline-6-carbonitrile compound (Yield 5.52 mg, 8.2%). 1H NMR (400 MHz, CDCl3): δ 1.64 (d, 3H, J=6.57 Hz), 3.29-3.10 (m, 6H), 3.48-3.37 (m, 2H), 3.68 (s, 3H), 3.90 (s, 3H), 4.53 (q, 1H, J=13.14, 5.81 Hz), 6.97 (d, 2H, J=2.02 Hz), 7.66 (d, 2H, J=8.84, Hz), 7.76 (d, 1H, J=8.59 Hz), 7.94 (dd, 1H J=8.59, 2.02 Hz), 8.57 (d, 1H, J=2.02 Hz). MS m/z calc. 467.16, found (ESI); 468.4 (M+1)+. Retention time 2.75 minutes.

Workup

  1. additionwas added KI (34.0 mg, 0.21 mmol)
  2. temperatureThe reaction was heated for 18 hours
  3. concentrationThe solution was concentrated under reduced pressure
  4. customThe residue was partitioned between water (2 ml) and dichloromethane (5 ml)
  5. dry with materialThe organic layer was dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe solvent was removed under vacuum
  9. dissolutionThe resulting residue was dissolvent in DMSO (2 ml)
  10. custompurified by HPLC (Gilson-215, 0.035% TFA in acetonitrile and 0.05% water as mobile phase)
  11. customThe product was collected
  12. customdried under reduced pressure

Sources & evidence

ORD record
ord-0b4ad67b86e742b0ba9d69e8bac8e6b4
Source dataset
uspto-grants-2014_02
Patent number
US08642609B2

Reaction notes

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