Acetonitrile → HCID 21527056, compound

HRID 1659137Notes

Reaction equation

HRID 1659137 reaction equation
[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([N:12]3[CH:16]([OH:17])[C:15]4[S:18][CH2:19][CH2:20][S:21][C:14]=4[C:13]3=[O:22])=[N:9]2)=[CH:4][CH:3]=1.[H-].[Na+].Cl[C:26]([N:28]1[CH2:33][CH2:32][N:31]([CH3:34])[CH2:30][CH2:29]1)=[O:27].C(#N)C>O1CCCC1.CN(C)C=O>[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([N:12]3[CH:13]([O:22][C:26]([N:28]4[CH2:33][CH2:32][N:31]([CH3:34])[CH2:30][CH2:29]4)=[O:27])[C:14]4[S:21][CH2:20][CH2:19][S:18][C:15]=4[C:16]3=[O:17])=[N:9]2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 24758Sodium hydrideHCID 30169354-Methyl-1-piperazinecarbonyl chlorideHCID 21527025HCID 21527025, compound2×

Product 1

HCID 21527056HCID 21527056, compoundYield 56.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
5 °C

Procedure

6-(7-Chloroquinol-2-yl)-5-hydroxy-7-oxo-2,3,6,7-tetrahydro-1,4-dithiino[2,3-c]pyrrole (9.0 g.) is added over the course of half an hour, at 15°-20°C, to a suspension of sodium hydride (1.35 g.) in anhydrous tetrahydrofuran (250 cc.). The reaction mixture is diluted with anhydrous dimethylformamide (50 cc.). 6-(7-Chloroquinol-2-yl)5-hydroxy-7-oxo-2,3,6,7-tetrahydro-1,4-dithiino[2,3-c]pyrrole (a further 9.0 g.) is added over the course of half an hour, at 15°C, and then 1-chlorocarbonyl-4-methylpiperazine (25.0 g.) dissolved in anhydrous tetrahydrofuran (150 cc.) is added at 5°C. The reaction mixture is stirred for 4 hours at 5°C. After evaporating the tetrahydrofuran under reduced pressure (20 mm.Hg), the reaction mixture is treated with water (500 cc.). The gummy precipitate which has appeared is filtered off and taken up in an ice-cold 2N aqueous solution of methanesulphonic acid (350 cc.). The ice-cold aqueous acid solution is filtered and then rendered alkaline by adding 10N sodium hydroxide solution. The oil which separates out is extracted three times with methylene chloride (total 600 cc.). The organic solution is washed three times with distilled water (total 450 cc.), dried over anhydrous sodium sulphate, treated with decolourising charcoal (1.0 g.) and evaporated. The partially crystalline residue obtained (13.3 g.) is dissolved in boiling acetonitrile (170 cc.). After cooling for 2 hours at 2°C, the crystals which have appeared are filtered off, washed twice with ice-cold acetonitrile (total 40 cc.) and dried under reduced pressure (20 mm.Hg). 6-(7-Chloroquinol-2-yl)-5-(4-methylpiperazin-1-yl)carbonyloxy-7-oxo-2,3,6,7-tetrahydro-1,4-dithiino[2,3-c]pyrrole (6.9 g.), melting at 192°C, is thus obtained.

Workup

  1. addition) is added over the course of half an hour, at 15°C
  2. additionis added at 5°C
  3. customAfter evaporating the tetrahydrofuran under reduced pressure (20 mm.Hg)
  4. additionthe reaction mixture is treated with water (500 cc.)
  5. filtrationThe gummy precipitate which has appeared is filtered off
  6. filtrationThe ice-cold aqueous acid solution is filtered
  7. additionby adding 10N sodium hydroxide solution
  8. extractionThe oil which separates out is extracted three times with methylene chloride (total 600 cc.)
  9. washThe organic solution is washed three times with distilled water (total 450 cc.)
  10. dry with materialdried over anhydrous sodium sulphate
  11. additiontreated with decolourising charcoal (1.0 g.)
  12. customevaporated
  13. customThe partially crystalline residue obtained (13.3 g.)
  14. dissolutionis dissolved
  15. temperatureAfter cooling for 2 hours at 2°C
  16. filtrationthe crystals which have appeared are filtered off
  17. washwashed twice with ice-cold acetonitrile (total 40 cc.)
  18. customdried under reduced pressure (20 mm.Hg)

Sources & evidence

ORD record
ord-5e8af1c5ee054b8aacdee84fff2111a7
Source dataset
uspto-grants-1976_06
Patent number
US03966931

Reaction notes

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