Dimethylcarbamoyl Chloride → 3-(1-(4-(5,7-Dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)phenyl)piperidin-4-yl)-1,1-dimethylurea

HRID 591614Notes

Reaction equation

HRID 591614 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]3[NH:23][C:22](=[O:24])[C:21]4[C:16](=[CH:17][C:18]([O:27][CH3:28])=[CH:19][C:20]=4[O:25][CH3:26])[N:15]=3)=[CH:10][CH:9]=2)[CH2:4][CH2:3]1.[CH3:29][N:30]([CH3:34])[C:31](Cl)=[O:32].CCN(CC)CC.[OH-].[Na+]>C1COCC1>[CH3:26][O:25][C:20]1[CH:19]=[C:18]([O:27][CH3:28])[CH:17]=[C:16]2[C:21]=1[C:22](=[O:24])[NH:23][C:14]([C:11]1[CH:12]=[CH:13][C:8]([N:5]3[CH2:4][CH2:3][CH:2]([NH:1][C:31](=[O:32])[N:30]([CH3:34])[CH3:29])[CH2:7][CH2:6]3)=[CH:9][CH:10]=1)=[N:15]2

Participants

6

Reactant 4

HCID 6598Dimethylcarbamoyl ChlorideHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 1363480492-(4-(4-aminopiperidin-1-yl)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one

Product 1

HCID 1359390923-(1-(4-(5,7-Dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)phenyl)piperidin-4-yl)-1,1-dimethylureaYield 51.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 2-(4-(4-aminopiperidin-1-yl)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one (0.105 g, 0.28 mmol), dimethylcarbamic chloride (0.032 g, 0.30 mmol), and Et3N (0.085 g, 0.84 mmol) in THF (10 mL) was stirred at room temperature for 18 hours. The mixture was then heated at reflux for 24 hours, then cooled to room temperature. 2 M NaOH (20 mL) was added and the mixture was stirred for 30 minutes. The reaction mixture was adjusted to pH 8, extracted with CH2Cl2 (3×100 mL), dried over anhydrous MgSO4, filtered, and concentrated. The residue was dissolved in CHCl3/MeOH and concentrated, then CH3CN was added and concentrated to afford the title compound as a white solid (0.065 g, 51%): 1H NMR (300 MHz, CDCl3): δ 11.72 (s, 1H), 8.08 (d, J=9.0 Hz, 2H), 7.00 (d, J=9.0 Hz, 2H), 6.78 (d, J=2.2 Hz, 1H), 6.46 (d, J=2.2 Hz, 1H), 5.99 (d, J=7.8 Hz, 1H), 3.90-3.94 (m, 2H), 3.88 (s, 3H), 3.83 (s, 3H), 3.66-3.69 (m, 1H), 2.88-2.93 (m, 2H), 2.76 (s, 6H), 1.75-1.80 (m, 2H), 1.45-1.52 (m, 2H); ESI MS m/z 452 [M+H]+.

Workup

  1. temperatureThe mixture was then heated
  2. temperatureat reflux for 24 hours
  3. temperaturecooled to room temperature
  4. stirringthe mixture was stirred for 30 minutes
  5. extractionextracted with CH2Cl2 (3×100 mL)
  6. dry with materialdried over anhydrous MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. dissolutionThe residue was dissolved in CHCl3/MeOH
  10. concentrationconcentrated
  11. additionCH3CN was added
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-cface09e543b45c9a3ff4a389bb6c1ba
Source dataset
uspto-grants-2016_01
Patent number
US09238640B2

Reaction notes

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