Sodium hydride → 4-((4,4-Dimethylcyclohexyl)oxy)-8-nitroquinazoline

HRID 1469731

Reaction equation

HRID 1469731 reaction equation
[CH3:1][C:2]1([CH3:9])[CH2:7][CH2:6][CH:5]([OH:8])[CH2:4][CH2:3]1.[H-].[Na+].Cl[C:13]1[C:22]2[C:17](=[C:18]([N+:23]([O-:25])=[O:24])[CH:19]=[CH:20][CH:21]=2)[N:16]=[CH:15][N:14]=1>C1COCC1>[CH3:1][C:2]1([CH3:9])[CH2:7][CH2:6][CH:5]([O:8][C:13]2[C:22]3[C:17](=[C:18]([N+:23]([O-:25])=[O:24])[CH:19]=[CH:20][CH:21]=3)[N:16]=[CH:15][N:14]=2)[CH2:4][CH2:3]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 136735Cyclohexanol, 4,4-dimethyl-HCID 114584714-Chloro-8-nitroquinazoline

Product 1

HCID 866922314-((4,4-Dimethylcyclohexyl)oxy)-8-nitroquinazolineYield 48.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4,4-dimethylcyclohexanol (140 mg, 1.097 mmol) in THF (2 mL) was added NaH (43 mg, 1.097 mmol, 60% in mineral oil) at 0° C. Then the reaction mixture was stirred at that temperature for 20 min and 4-chloro-8-nitroquinazoline (Intermediate-7, step 2, 115 mg, 0.549 mmol) was added to the reaction mixture. Then the reaction mixture was stirred at 0-5° C. for 4 h and then at rt for 12 h. Then the reaction mixture was quenched with water and was extracted with chloroform. The organic layer was washed with brine, separated, dried, filtered and concentrated. The residue was purified by column chromatography using chloroform to afford 80 mg of the title product. 1H NMR (300 MHz, DMSO d6): δ 8.89 (s, 1H), 8.49-8.46 (d, J=7.8 Hz, 1H), 8.45-8.42 (d, J=7.8 Hz, 1H), 7.86-7.80 (t, J=8.4 Hz, 1H), 5.41 (m, 1H), 1.94 (m, 2H), 1.82-1.79 (m, 2H), 1.54 (m, 2H), 1.37-1.34 (m, 2H), 0.99 (s, 3H), 0.67 (s, 3H); MS (m/z): 301.93 (M+H)+.

Workup

  1. stirringThen the reaction mixture was stirred at 0-5° C. for 4 h
  2. waitat rt for 12 h
  3. customThen the reaction mixture was quenched with water
  4. extractionwas extracted with chloroform
  5. washThe organic layer was washed with brine
  6. customseparated
  7. customdried
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-ffd9f05d325c445a9bed5834db9e123b
Source dataset
uspto-grants-2015_04
Patent number
US09006257B2

Linked notes

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