Dimethylformamide → 4-Chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazoline

HRID 1357720Notes

Reaction equation

HRID 1357720 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1)[N:9]=[CH:8][NH:7][C:6]2=O.CN(C)C=O.S(Cl)([Cl:31])=O>>[Cl:31][C:6]1[C:5]2[C:10](=[CH:11][C:12]([O:13][CH2:14][CH2:15][CH2:16][N:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[C:3]([O:2][CH3:1])[CH:4]=2)[N:9]=[CH:8][N:7]=1

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 1354371166-Methoxy-7-(3-morpholinopropoxy)-3,4-dihydroquinazolin-4-one

Product 1

HCID 118239414-Chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazoline

Procedure

6-Methoxy-7-(3-morpholinopropoxy)-3,4-dihydroquinazolin-4-one (1.22 g) was stirred in thionyl chloride (10 ml) with dimethylformamide (0.1 ml) at 85° C. for 1 hour. The reaction was evaporated to dryness, and then azeotroped with toluene. The residue was partitioned between methylene chloride and saturated sodium bicarbonate. The organic phase was separated and evaporated to dryness. The saturated sodium bicarbonate phase was basified with 2M sodium hydroxide and was extracted with methylene chloride. The two organic phases were combined and dried over sodium sulphate, filtered and the filtrate evaporated to dryness. This residue was purified by eluting through a silica column with 5% methanol in methylene chloride to yield 4-chloro-6-methoxy-7-(3-morpholinopropoxy)quinazoline as a solid, (0.5 g, 39%); NMR: 1.95 (m, 2H), 2.4 (broad m, 6H), 3.55 (m, 4H), 3.98 (s, 3H), 4.26 (t, 2H), 7.36 (s, 1H), 7.41 (s, 1H), 8.83 (s, 1H); m/s: M+H+ 338, 340.

Workup

  1. customThe reaction was evaporated to dryness
  2. customazeotroped with toluene
  3. customThe residue was partitioned between methylene chloride and saturated sodium bicarbonate
  4. customThe organic phase was separated
  5. customevaporated to dryness
  6. extractionwas extracted with methylene chloride
  7. dry with materialdried over sodium sulphate
  8. filtrationfiltered
  9. customthe filtrate evaporated to dryness
  10. customThis residue was purified
  11. washby eluting through a silica column with 5% methanol in methylene chloride

Sources & evidence

ORD record
ord-c4d3b281863e44bcb5cd56f88eb36dad
Source dataset
uspto-grants-2003_07
Patent number
US06593333B1

Reaction notes

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