2-Chloro-N,N-dimethylpyrimidin-4-amine → 4-Amino-6,7-dimethoxy-2-[4-(4-dimethylaminopyrimidin-2-yl)piperazin-1-yl]quinoline dihydrochloride dihydrate

HRID 1788986Notes

Reaction equation

HRID 1788986 reaction equation
[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[C:4]([N:16]2[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]2)[CH:3]=1.[Cl:22][C:23]1[N:28]=[C:27]([N:29]([CH3:31])[CH3:30])[CH:26]=[CH:25][N:24]=1>C(O)CCC>[OH2:12].[OH2:12].[ClH:22].[ClH:22].[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[C:4]([N:16]2[CH2:17][CH2:18][N:19]([C:23]3[N:28]=[C:27]([N:29]([CH3:31])[CH3:30])[CH:26]=[CH:25][N:24]=3)[CH2:20][CH2:21]2)[CH:3]=1

Participants

4

Reactant 2

HCID 959752-Chloro-N,N-dimethylpyrimidin-4-amineHCID 140689984-Amino-6,7-dimethoxy-2-(piperazin-1-yl)quinoline

Product 1

HCID 201311224-Amino-6,7-dimethoxy-2-[4-(4-dimethylaminopyrimidin-2-yl)piperazin-1-yl]quinoline dihydrochloride dihydrateYield 25.2%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

4-Amino-6,7-dimethoxy-2-(piperazin-1-yl)quinoline (1.26 g) and 2-chloro-4-dimethylaminopyrimidine (0.76 g) in n-butanol (60 ml) were heated under reflux for 16 hours. The mixture was then evaporated in vacuo, the residue partitioned between chloroform and sodium carbonate solution (10%) and the aqueous phase extracted with chloroform. The combined extracts were washed with water, dried (Na2SO4), evaporated in vacuo and the residue chromatographed on silica gel (Merck 9385). Elution with chloroform-methanol (100:0→95.5) followed by treatment of the product with ethereal hydrogen chloride and recrystallisation from methanol gave 4-amino-6,7-dimethoxy-2-[4-(4-dimethylaminopyrimidin-2-yl)piperazin-1-yl]quinoline dihydrochloride dihydrate (0.19 g), m.p. 260°-263°.

Workup

  1. temperatureunder reflux for 16 hours
  2. customThe mixture was then evaporated in vacuo
  3. customthe residue partitioned between chloroform and sodium carbonate solution (10%)
  4. extractionthe aqueous phase extracted with chloroform
  5. washThe combined extracts were washed with water
  6. dry with materialdried (Na2SO4)
  7. customevaporated in vacuo
  8. customthe residue chromatographed on silica gel (Merck 9385)
  9. washElution with chloroform-methanol (100:0→95.5)
  10. customfollowed by treatment of the product with ethereal hydrogen chloride and recrystallisation from methanol

Sources & evidence

ORD record
ord-8d642450138948b08e61b7cdec6f0498
Source dataset
uspto-grants-1987_08
Patent number
US04686228

Reaction notes

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