Pyridine → HCID 13017837, compound

HRID 2286215Notes

Reaction equation

HRID 2286215 reaction equation
C(N(CC)CC)C.[OH:8][CH:9]1[N:13]([C:14]2[CH:23]=[CH:22][C:21]3[C:16](=[N:17][C:18]([CH3:24])=[CH:19][CH:20]=3)[N:15]=2)[C:12](=[O:25])[C:11]2[S:26][CH2:27][CH:28]([O:31][CH3:32])[CH2:29][S:30][C:10]1=2.Cl.Cl[C:35]([N:37]1[CH2:42][CH2:41][N:40]([CH3:43])[CH2:39][CH2:38]1)=[O:36].N1C=CC=CC=1>C(Cl)Cl>[CH3:32][O:31][CH:28]1[CH2:29][S:30][C:10]2[C:9](=[O:8])[N:13]([C:14]3[CH:23]=[CH:22][C:21]4[C:16](=[N:17][C:18]([CH3:24])=[CH:19][CH:20]=4)[N:15]=3)[CH:12]([O:25][C:35]([N:37]3[CH2:42][CH2:41][N:40]([CH3:43])[CH2:39][CH2:38]3)=[O:36])[C:11]=2[S:26][CH2:27]1

Participants

6

Reactant 4

HCID 1049PyridineHCID 8471TriethylamineHCID 30169344-Methylpiperazine-1-carbonyl chloride monohydrochloride2×HCID 13017828HCID 13017828, compound

Product 1

HCID 13017837HCID 13017837, compoundYield 43.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
45 °C

Procedure

Triethylamine (24.5 cc) is added, at about 15° C., to a suspension of 6-hydroxy-3-methoxy-7-(7-methyl-1,8-naphthyridin-2-yl)-8-oxo-3,4,7,8-tetrahydro-2H,6H-1,4-dithiepino[2,3-c]pyrrole (7.3 g) and 1-chlorocarbonyl-4-methylpiperazine hydrochloride (11.7 g) in anhydrous methylene chloride (300 cc), and anhydrous pyridine (130 cc) is then added to the resulting mixture. The mixture is heated at 45° C. for 3 hours. 1-Chlorocarbonyl-4-methylpiperazine hydrochloride (6.0 g) is then added and the mixture is heated for a further 1/2 hour at 45° C. After cooling, the mixture is diluted by adding methylene chloride (300 cc). The organic phase is washed three times with distilled water (total 600 cc), dried over sodium sulphate and evaporated. The resulting residue (25.0 g) is dissolved in boiling acetonitrile (70 cc). After cooling the solution for 48 hours at 2° C., the resulting crystals are filtered off, washed twice with ice-cooled acetonitrile (total 20 cc) and dried under reduced pressure (20 mm Hg) at 20° C. The resulting product (5.25 g; m.p. 220° C.) is dissolved in methylene chloride (100 cc) and the solution is filtered through silica (0.2-0.5 mm; 200 g) contained in a column of diameter 2.1 cm. Elution is carried out with methylene chloride (400 cc); the eluate is discarded. Elution is continued with a mixture of methylene chloride (784 cc) and methanol (16 cc); this eluate is evaporated under reduced pressure (20 mm Hg) at a temperature below 60° C. The residue is dried under reduced pressure (0.2 mm Hg) at 50° C. 3-Methoxy-7-(7-methyl-1,8-naphthyridin-2-yl)-6-(4-methylpiperazin-1-yl)carbonyloxy-8-oxo-3,4,7,8-tetrahydro-2H,6H-1,4-dithiepino[2,3-c]pyrrole (4.2 g), melting at 225° C., is obtained.

Workup

  1. additionis then added to the resulting mixture
  2. temperaturethe mixture is heated for a further 1/2 hour at 45° C
  3. temperatureAfter cooling
  4. additionthe mixture is diluted
  5. washThe organic phase is washed three times with distilled water (total 600 cc)
  6. dry with materialdried over sodium sulphate
  7. customevaporated
  8. dissolutionThe resulting residue (25.0 g) is dissolved
  9. temperatureAfter cooling the solution for 48 hours at 2° C.
  10. filtrationthe resulting crystals are filtered off
  11. washwashed twice with ice-
  12. temperaturecooled acetonitrile (total 20 cc)
  13. customdried under reduced pressure (20 mm Hg) at 20° C
  14. dissolutionThe resulting product (5.25 g; m.p. 220° C.) is dissolved in methylene chloride (100 cc)
  15. filtrationthe solution is filtered through silica (0.2-0.5 mm; 200 g)
  16. washElution
  17. washElution
  18. additionis continued with a mixture of methylene chloride (784 cc) and methanol (16 cc)
  19. customthis eluate is evaporated under reduced pressure (20 mm Hg) at a temperature below 60° C
  20. customThe residue is dried under reduced pressure (0.2 mm Hg) at 50° C

Sources & evidence

ORD record
ord-f4c7374f9337489eb6f512fd407f4908
Source dataset
uspto-grants-1982_04
Patent number
US04327095

Reaction notes

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