Triethylamine → 4-Amino-2-[4-(1,4-benzodioxan-2-carbonyl)piperazin-1-yl]-6,7-dimethoxyquinoline hydrochloride hydrate

HRID 542205

Reaction equation

HRID 542205 reaction equation
[O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][CH2:3][CH:2]1[C:11]([Cl:13])=[O:12].[NH2:14][C:15]1[C:24]2[C:19](=[CH:20][C:21]([O:27][CH3:28])=[C:22]([O:25][CH3:26])[CH:23]=2)[N:18]=[C:17]([N:29]2[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]2)[CH:16]=1.C(N(CC)CC)C>C(Cl)(Cl)Cl>[OH2:1].[ClH:13].[NH2:14][C:15]1[C:24]2[C:19](=[CH:20][C:21]([O:27][CH3:28])=[C:22]([O:25][CH3:26])[CH:23]=2)[N:18]=[C:17]([N:29]2[CH2:30][CH2:31][N:32]([C:11]([CH:2]3[O:1][C:6]4[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=4[O:4][CH2:3]3)=[O:12])[CH2:33][CH2:34]2)[CH:16]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 27354472,3-Dihydro-1,4-benzodioxin-2-carbonyl chlorideHCID 140689984-Amino-6,7-dimethoxy-2-(piperazin-1-yl)quinoline

Product 1

HCID 201311304-Amino-2-[4-(1,4-benzodioxan-2-carbonyl)piperazin-1-yl]-6,7-dimethoxyquinoline hydrochloride hydrateYield 29.4%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Procedure

A solution of 1,4-benzodioxan-2-carbonyl chloride (0.75 g) in chloroform (10 ml) was added dropwise to a stirred solution of 4-amino-6,7-dimethoxy-2-(piperazin-1-yl)quinoline (1.0 g) in chloroform (50 ml) with triethylamine (1.06 g) at 5°-10°. The reaction was stirred at 5°-10° for one hour, then allowed to attain room temperature and stirred overnight. The mixture was then evaporated in vacuo and the residue partitioned between chloroform (50 ml) and sodium carbonate solution (10%, 50 ml). The chloroform layer was separated, the aqueous phase extracted with chloroform (2×50 ml), the extracts combined, washed with brine, dried (Na2SO4) and evaporated in vacuo. The residue was then taken up in chloroform and chromatographed on silica (Merck 9385, 60 g) eluting with chloroform/methanol (100:0→97:3). A solution of the purified product in chloroform was treated with ethereal hydrogen chloride, evaporated in vacuo and the residue recrystallised from isopropanol to give 4-amino-2-[ 4-(1,4-benzodioxan-2-carbonyl)piperazin-1-yl]-6,7-dimethoxyquinoline hydrochloride hydrate (0.28 g), m.p. 201°.

Workup

  1. customto attain room temperature
  2. stirringstirred overnight
  3. customThe mixture was then evaporated in vacuo
  4. customthe residue partitioned between chloroform (50 ml) and sodium carbonate solution (10%, 50 ml)
  5. customThe chloroform layer was separated
  6. extractionthe aqueous phase extracted with chloroform (2×50 ml)
  7. washwashed with brine
  8. dry with materialdried (Na2SO4)
  9. customevaporated in vacuo
  10. customchromatographed on silica (Merck 9385, 60 g)
  11. washeluting with chloroform/methanol (100:0→97:3)
  12. additionA solution of the purified product in chloroform was treated with ethereal hydrogen chloride
  13. customevaporated in vacuo
  14. customthe residue recrystallised from isopropanol

Sources & evidence

ORD record
ord-92c931bc07db44f19c3486c407731037
Source dataset
uspto-grants-1987_04
Patent number
US04656174

Linked notes

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