1-((4-Methoxyphenyl)sulfonyl)piperazine → 6-Methanesulfonyl-2-{1-[4-(4-methoxy-benzenesulfonyl)-piperazin-1-yl]-ethyl}-3-methyl-3H-quinazolin-4-one

HRID 238208Notes

Reaction equation

HRID 238208 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]([S:16]([CH3:19])(=[O:18])=[O:17])[CH:10]=2)[N:5]=1)[CH3:3].[CH3:20][O:21][C:22]1[CH:27]=[CH:26][C:25]([S:28]([N:31]2[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]2)(=[O:30])=[O:29])=[CH:24][CH:23]=1>C(#N)C>[CH3:19][S:16]([C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[N:5]=[C:4]([CH:2]([N:34]1[CH2:33][CH2:32][N:31]([S:28]([C:25]3[CH:24]=[CH:23][C:22]([O:21][CH3:20])=[CH:27][CH:26]=3)(=[O:30])=[O:29])[CH2:36][CH2:35]1)[CH3:3])[N:13]([CH3:14])[C:12]2=[O:15])(=[O:18])=[O:17]

Participants

4

Reactant 2

HCID 7975601-((4-Methoxyphenyl)sulfonyl)piperazineHCID 599932062-(1-Bromo-ethyl)-6-methanesulfonyl-3-methyl-3H-quinazolin-4-one

Product 1

HCID 599932796-Methanesulfonyl-2-{1-[4-(4-methoxy-benzenesulfonyl)-piperazin-1-yl]-ethyl}-3-methyl-3H-quinazolin-4-oneYield 55.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

In a test tube containing of 2-(1-Bromo-ethyl)-6-methanesulfonyl-3-methyl-3H-quinazolin-4-one (40.0 mg, 0.12 mmol) in acetonitrile (2 ml) was added KI (28.0 mg, 0.18 mmol), and (1-(4-Methoxy-benzenesulfonyl)-piperazine (39.6 mg, 0.18 mmol). The reaction was heated at 80° C. 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 6-Methanesulfonyl-2-{1-[4-(4-methoxy-benzenesulfonyl)-piperazin-1-yl]-ethyl}-3-methyl-3H-quinazolin-4-one (Yield 32.4 mg, 55.2%). 1H NMR (400 MHz, CDCl3): δ 1.82 (d, 3H, J=7.07 Hz), 3.12 (s, 3H), 3.64-3.40 (m, 4H), 3.70 (s, 3H), 4.00-3.86 (m, 7H), 4.89 (q, 1H, J=14.40, 6.03 Hz), 7.05 (d, 2H, J=9.09 Hz), 7.68 (d, 2H, J=9.09, Hz), 7.84 (d, 1H, J=8.84 Hz), 8.25 (dd, 1H J=8.84, 2.02 Hz), 8.82 (d, 1H, J=2.02 Hz). MS m/z calc. 490.1, found (ESI); 491.2 (M+1)+. Retention time 2.17 minutes.

Workup

  1. additionwas added KI (28.0 mg, 0.18 mmol)
  2. concentrationThe solution was concentrated under reduced pressure
  3. customThe residue was partitioned between water (2 ml) and dichloromethane (5 ml)
  4. dry with materialThe organic layer was dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe solvent was removed under vacuum
  8. dissolutionThe resulting residue was dissolvent in DMSO (2 ml)
  9. custompurified by HPLC (Gilson-215, 0.035% TFA in acetonitrile and 0.05% water as mobile phase)
  10. customThe product was collected
  11. customdried under reduced pressure

Sources & evidence

ORD record
ord-81328c0b7a2b4173bce32707b3b7bcea
Source dataset
uspto-grants-2014_02
Patent number
US08642609B2

Reaction notes

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