Methyl iodide → 4-(Methylthio)-5,6-dihydrofuro[2,3-h]quinazolin-2-amine

HRID 1036377Notes

Reaction equation

HRID 1036377 reaction equation
[O:1]1[C:5]2[CH2:6][CH2:7][CH2:8][C:9](=O)[C:4]=2[CH:3]=[CH:2]1.[C:11](=[S:13])=S.IC.[H-].[Na+].[N+]([O-])(O)=O.[NH2:22][C:23]([NH2:25])=[NH:24].[O-][CH2:27]C.[Na+]>O1CCCC1.C(O)C.O>[CH3:27][S:13][C:11]1[C:8]2[CH2:7][CH2:6][C:5]3[O:1][CH:2]=[CH:3][C:4]=3[C:9]=2[N:22]=[C:23]([NH2:25])[N:24]=1

Participants

10

Reactant 6

HCID 6328Methyl iodideHCID 6348Carbon DisulfideHCID 10481Guanidine NitrateHCID 24758Sodium hydrideHCID 2723922Sodium ethoxideHCID 27335414,5,6,7-Tetrahydro-1-benzofuran-4-one

Product 1

HCID 685258504-(Methylthio)-5,6-dihydrofuro[2,3-h]quinazolin-2-amine

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 6,7-dihydro-4(5H)-benzofuranone (0.10 g, 0.73 mmol), carbon disulfide (0.048 mL, 0.80 mmol), and iodomethane (0.10 mL, 1.6 mmol) in tetrahydrofuran (1.8 mL) was treated with a 60% dispersion of sodium hydride in mineral oil (0.070 g, 1.8 mmol), stirred over night at ambient temperature and partitioned between saturated ammonium chloride and ethyl acetate. The organic layer was washed with brine, dried (magnesium sulfate), filtered and concentrated. The residue was treated with guanidine nitrate (0.36 g, 2.9 mmol), treated with 1.46 mL (2.2 mol) of 1.5 M sodium ethoxide in ethanol, heated to 80° C. overnight, cooled, diluted with water and extracted with dichloromethane (3×). The combined dichloromethane layers were dried (magnesium sulfate), filtered, concentrated and chromatographed using ethyl acetate in dichloromethane to provide the title compound: 1H NMR (300 MHz, CDCl3) δ 2.52 (s, 3H), 2.88-3.02 (m, 4H), 5.07 (br s, 2H), 6.87 (d, J=1.7 Hz, 1H), 7.37 (d, J=2.0 Hz, 1H); MS (DCI/NH3) m/z 234 (M+H)+.

Workup

  1. custompartitioned between saturated ammonium chloride and ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried (magnesium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. temperatureheated to 80° C. overnight
  7. temperaturecooled
  8. extractionextracted with dichloromethane (3×)
  9. dry with materialThe combined dichloromethane layers were dried (magnesium sulfate)
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customchromatographed

Sources & evidence

ORD record
ord-526b7dac4178448484a28c1fd12e6619
Source dataset
uspto-grants-2013_10
Patent number
US08546410B2

Reaction notes

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