Dimethylformamide → HCID 17974607, compound

HRID 1372987Notes

Reaction equation

HRID 1372987 reaction equation
[C:1]([O:4][CH:5]([CH2:21][N:22]1[CH2:27][CH2:26][N:25]([CH3:28])[CH2:24][CH2:23]1)[CH2:6][O:7][C:8]1[CH:17]=[C:16]2[C:11]([C:12](=O)[NH:13][CH:14]=[N:15]2)=[CH:10][C:9]=1[O:19][CH3:20])(=[O:3])[CH3:2].CN(C=O)C.S(Cl)([Cl:36])=O>>[C:1]([O:4][CH:5]([CH2:21][N:22]1[CH2:27][CH2:26][N:25]([CH3:28])[CH2:24][CH2:23]1)[CH2:6][O:7][C:8]1[CH:17]=[C:16]2[C:11]([C:12]([Cl:36])=[N:13][CH:14]=[N:15]2)=[CH:10][C:9]=1[O:19][CH3:20])(=[O:3])[CH3:2]

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 135788039HCID 135788039, compound

Product 1

HCID 17974607HCID 17974607, compoundYield 88%

Conditions

Temperature
80 °C

Procedure

A solution of 7-[2-acetoxy-3-(4-methylpiperazin-1-yl) propoxy]-6-methoxyquinazolin-4-one (930 mg, 2.4 mmol) in thionyl chloride (10 ml) containing DMF (150 μl) was heated at 80° C. for 5 hours. The volatiles were removed under vacuum and the residue azeotroped with toluene. The solid was partitioned between methylene chloride and water and the pH of the aqueous layer was adjusted to 7 with solid sodium bicarbonate. The organic layer was separated, washed with brine, dried (MgSO4) and evaporated. The residue was purified by column chromatography eluting with methylene chloride/methanol saturated with ammonia (95/5). The fractions containing the expected product were combined and the volatiles were removed under vacuum to give 7-[2-acetoxy-3-(4-methylpiperazin-1-yl)propoxy]-6-methoxy-4-chloroquinazoline (859 mg, 88%).

Workup

  1. customThe volatiles were removed under vacuum
  2. customthe residue azeotroped with toluene
  3. customThe solid was partitioned between methylene chloride and water
  4. customThe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried (MgSO4)
  7. customevaporated
  8. customThe residue was purified by column chromatography
  9. washeluting with methylene chloride/methanol saturated with ammonia (95/5)
  10. additionThe fractions containing the expected product
  11. customthe volatiles were removed under vacuum

Sources & evidence

ORD record
ord-d8a62535d27d4c0681c152632b3a79f4
Source dataset
uspto-grants-2007_01
Patent number
US07160889B2

Reaction notes

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