1-Piperazinecarboxaldehyde → 2-Cyclopropyl-7,8-dihydro-4-(1-piperazinyl)-6H-thiopyrano[3,2-d]pyrimidine dihydrochloride hemihydrate

HRID 982134Notes

Reaction equation

HRID 982134 reaction equation
[CH:1]1([C:4]2[N:5]=[C:6]([Cl:14])[C:7]3[S:13][CH2:12][CH2:11][CH2:10][C:8]=3[N:9]=2)[CH2:3][CH2:2]1.[N:15]1([CH:21]=[O:22])[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1>C(#N)C>[OH2:22].[ClH:14].[ClH:14].[CH:1]1([C:4]2[N:5]=[C:6]([N:15]3[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]3)[C:7]3[S:13][CH2:12][CH2:11][CH2:10][C:8]=3[N:9]=2)[CH2:3][CH2:2]1.[CH:1]1([C:4]2[N:5]=[C:21]([N:15]3[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]3)[C:7]3[S:13][CH2:12][CH2:11][CH2:10][C:8]=3[N:9]=2)[CH2:2][CH2:3]1.[ClH:14].[ClH:14]

Participants

4

Reactant 2

HCID 821911-PiperazinecarboxaldehydeHCID 148788032-Cyclopropyl-4-chloro-7,8-dihydro-6H-thiopyrano[3,2-d]pyrimidine

Product 1

HCID 678372692-Cyclopropyl-7,8-dihydro-4-(1-piperazinyl)-6H-thiopyrano[3,2-d]pyrimidine dihydrochloride hemihydrate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
95 °C

Procedure

A solution of product from Step B (12.1 g), and 1-piperazinecarboxaldehyde (11 ml) in acetonitrile (15 ml) was heated at reflux for 16 hours. The acetonitrile was distilled at reduced pressure and the gummy residue treated with H2O (280ml) and concentrated hydrochloric acid (70 ml) and heated at 95° C. for 1 hour. The solvent was distilled at reduced pressure, the residue treated with ammonium hydroxide, extracted with CH2Cl2 washed with water, brine and dried over K2CO3. The CH2Cl2 was distilled at reduced pressure and the residue chromatographed on silica gel (320 g) eluting with CHCl3.CH3OH (9:1). The pertinent fractions were combined and evaporated, the product dissolved in ethanol (60 ml), treated with 10N sthanolic HCl (10 ml) and ether (60 ml) to give 12.5 g of title compound which melted at 205°-207° C. after recrystallization from ethanol-ether.

Workup

  1. temperatureat reflux for 16 hours
  2. distillationThe acetonitrile was distilled at reduced pressure
  3. additionthe gummy residue treated with H2O (280ml) and concentrated hydrochloric acid (70 ml)
  4. distillationThe solvent was distilled at reduced pressure
  5. additionthe residue treated with ammonium hydroxide
  6. extractionextracted with CH2Cl2
  7. washwashed with water, brine
  8. dry with materialdried over K2CO3
  9. distillationThe CH2Cl2 was distilled at reduced pressure
  10. customthe residue chromatographed on silica gel (320 g)
  11. washeluting with CHCl3
  12. customevaporated
  13. dissolutionthe product dissolved in ethanol (60 ml)
  14. additiontreated with 10N sthanolic HCl (10 ml) and ether (60 ml)

Sources & evidence

ORD record
ord-c2b10121b5904e09af155f0cd5132136
Source dataset
uspto-grants-1991_02
Patent number
US04994464

Reaction notes

Loading…