Methyl iodide → 6-bromo-2-(methylthio)-3-[(tetrahydro-2-furanyl)methyl]-4(3H)-quinazolinone

HRID 1108251Notes

Reaction equation

HRID 1108251 reaction equation
[C:1](=O)([O-])[O-].[K+].[K+].IC.[Br:9][C:10]1[CH:11]=[C:12]2[C:17](=[CH:18][CH:19]=1)[NH:16][C:15](=[S:20])[N:14]([CH2:21][CH:22]1[CH2:26][CH2:25][CH2:24][O:23]1)[C:13]2=[O:27]>CN(C)C=O>[Br:9][C:10]1[CH:11]=[C:12]2[C:17](=[CH:18][CH:19]=1)[N:16]=[C:15]([S:20][CH3:1])[N:14]([CH2:21][CH:22]1[CH2:26][CH2:25][CH2:24][O:23]1)[C:13]2=[O:27]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 4444271HCID 4444271, compound

Product 1

HCID 211962806-bromo-2-(methylthio)-3-[(tetrahydro-2-furanyl)methyl]-4(3H)-quinazolinone

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Potassium carbonate (6.0 g, 44 mmol), iodomethane (2.5 g, 1.1 mL, 17.6 mmol), and the title compound of Step A (3.0 g, 8.8 mmol) were combined in dimethylformamide (90 mL) and stirred for 2 h at room temperature. The reaction mixture was then concentrated to dryness under reduced pressure, and the ensuing residue was partitioned between 200 mL each of ethyl acetate and water. The phases were separated and the organic phase was subsequently washed with saturated aqueous NaCl and dried over Na2SO4 (anhydrous). Following solvent removal under reduced pressure and trituration of the resulting material with cold hexanes, 2.8 g of the title compound of Step B, a compound of the invention, was obtained as a solid melting at 68-72° C. 1H NMR (300 MHz, CDCl3):δ6 1.64-1.83 (m,1H), 1.80-2.18 (m,3H), 2.62 (s,3H), 3.78 (dd,1H), 3.96 (dd,1H), 4.17 (dd,1H), 4.21 (dd,1H), 4.38-4.50 (m,1H), 7.41 (d,1H), 7.73 (dd,1H), 8.36 (d,1H).

Workup

  1. concentrationThe reaction mixture was then concentrated to dryness under reduced pressure
  2. customthe ensuing residue was partitioned between 200 mL each of ethyl acetate and water
  3. customThe phases were separated
  4. washthe organic phase was subsequently washed with saturated aqueous NaCl
  5. dry with materialdried over Na2SO4 (anhydrous)
  6. customFollowing solvent removal under reduced pressure and trituration of the resulting material with cold hexanes, 2.8 g of the title compound of Step B

Sources & evidence

ORD record
ord-d75435b0ea2743389dd128c1bb00a1c3
Source dataset
uspto-grants-2000_05
Patent number
US06066638

Reaction notes

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