Thionyl Chloride → HCID 20351340, compound

HRID 1448963Notes

Reaction equation

HRID 1448963 reaction equation
[CH3:1][O:2][C:3]1[CH:15]=[CH:14][C:6]2[O:7][CH:8]([C:11]([Cl:13])=[O:12])[CH2:9][O:10][C:5]=2[CH:4]=1.S(Cl)(Cl)=O.[NH2:20][C:21]1[C:30]2[C:25](=[CH:26][C:27]([O:33][CH3:34])=[C:28]([O:31][CH3:32])[CH:29]=2)[N:24]=[C:23]([N:35]2[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]2)[N:22]=1>ClCCl>[OH2:2].[ClH:13].[NH2:20][C:21]1[C:30]2[C:25](=[CH:26][C:27]([O:33][CH3:34])=[C:28]([O:31][CH3:32])[CH:29]=2)[N:24]=[C:23]([N:35]2[CH2:40][CH2:39][N:38]([C:11]([CH:8]3[O:7][C:6]4[CH:14]=[CH:15][C:3]([O:2][CH3:1])=[CH:4][C:5]=4[O:10][CH2:9]3)=[O:12])[CH2:37][CH2:36]2)[N:22]=1

Participants

5

Reactant 3

HCID 24386Thionyl ChlorideHCID 6162672-(1-Piperazinyl)-4-amino-6,7-dimethoxyquinazolineHCID 15591649HCID 15591649, compound

Product 1

HCID 20351340HCID 20351340, compoundYield 37.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 6-methoxy-1,4-benzodioxan-2-carbonyl chloride (2.17 g.) (prepared from the acid and thionyl chloride) in dichloromethane (25 ml.) was added dropwise to a stirred suspension of 4-amino-2-piperazin-1-yl-6,7-dimethoxy-quinazoline (2.48 g.) in methylene chloride (50 ml.) at room temperature. After the addition was complete, the mixture was stirred at room temperature for 4 hours, then filtered and the solid suspended in aqueous potassium carbonate solution and extracted with chloroform. The combined extracts were washed with water, dried (Na2SO4) and evaporated in vacuo to leave a solid residue (4.15 g.) which was chromatographed on silica (160 g.) and eluted with chloroform then chloroform-methanol (2.5%). Similar fractions (t.l.c.) were combined, evaporated in vacuo then the residue taken up in ethyl acetate-methanol and treated with ethereal hydrogen chloride. Addition of further ether followed by cooling yielded a solid which was collected and recrystallized from methanol to give 4-amino-2-[4-(6-methoxy-1,4-benzodioxan-2-carbonyl)piperazin-1-yl-]-6,7-dimethoxyquinazoline hydrochloride hydrate (0.95 g.), m.p. 220°-222° C.

Workup

  1. additionAfter the addition
  2. filtrationfiltered
  3. extractionextracted with chloroform
  4. washThe combined extracts were washed with water
  5. dry with materialdried (Na2SO4)
  6. customevaporated in vacuo
  7. customto leave a solid residue (4.15 g.) which
  8. customwas chromatographed on silica (160 g.)
  9. washeluted with chloroform
  10. customevaporated in vacuo
  11. additiontreated with ethereal hydrogen chloride
  12. additionAddition of further ether
  13. temperatureby cooling
  14. customyielded a solid which
  15. customwas collected
  16. customrecrystallized from methanol

Sources & evidence

ORD record
ord-81cf95504f244ba8b2cbe8ad8cfdced6
Source dataset
uspto-grants-1980_02
Patent number
US04188390

Reaction notes

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