2,5-Dimethylpyrrolidine → HCID 15925277, compound

HRID 704186Notes

Reaction equation

HRID 704186 reaction equation
CS(O[CH2:6][CH:7]([N:9]1[C:22]2[CH:21]=[C:20]([C:23]#[N:24])[CH:19]=[CH:18][C:17]=2[S:16][C:15]2[C:10]1=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH3:8])(=O)=O.[CH3:25][CH:26]1[CH2:30][CH2:29][CH:28]([CH3:31])[NH:27]1>C1(C)C=CC=CC=1.C(OCC)(=O)C>[CH3:25][CH:26]1[CH2:30][CH2:29][CH:28]([CH3:31])[N:27]1[CH2:6][CH:7]([N:9]1[C:22]2[CH:21]=[C:20]([C:23]#[N:24])[CH:19]=[CH:18][C:17]=2[S:16][C:15]2[C:10]1=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH3:8]

Participants

5

Reactant 2

HCID 960342,5-DimethylpyrrolidineHCID 145021392-(2-Cyano-10-phenothiazinyl)propyl mesylate

Product 1

HCID 15925277HCID 15925277, compoundYield 19.8%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 2-(2-cyano-10-phenothiazinyl)-1-propyl methanesulphonate (5 g) and (2RS,5RS)-2,5-dimethylpyrrolidine (5 g) in toluene (50 cc) is heated for 4 days to a temperature in the region of 100° C. After cooling, the reaction mixture is diluted with ethyl acetate (200 cc) and extracted successively with N aqueous hydrochloric acid solution (50 cc and 2×25 cc). The combined aqueous phases are alkalinized with 10N aqueous sodium hydroxide solution to pH 13, and extracted successively with ethyl ether (200 cc and 50 cc). The combined organic phases are dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C. The residual yellow gum (2.8 g) is purified by chromatography on a column (height: 30 cm; diameter: 2 cm) of silica gel (0.2-0.063 mm), eluting with a mixture (80:20 by volume) (500 cc) of cyclohexane and ethyl acetate and collecting 30-cc fractions. The combined fractions 5 to 11 are concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C. The viscous yellow residue (2.4 g) is dissolved in isopropyl ether (15 cc) under reflux. The solution is cooled and then kept for 2 hours at a temperature in the region of 5° C. The crystals formed are drained, washed with isopropyl ether (2 cc) and dried under reduced pressure (5 mm Hg; 0.68 kPa) at 40° C. 10-((2RS)-1-[(2RS,5RS)-2,5-dimethyl-1-pyrrolidinyl]-2-propyl}-2-phenothiazine carbonitrile (1 g) is thereby obtained in the form of pale yellow crystals, m.p. 105° C.

Workup

  1. temperatureAfter cooling
  2. extractionextracted successively with N aqueous hydrochloric acid solution (50 cc and 2×25 cc)
  3. extractionextracted successively with ethyl ether (200 cc and 50 cc)
  4. dry with materialThe combined organic phases are dried over magnesium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C
  7. customThe residual yellow gum (2.8 g) is purified by chromatography on a column (height: 30 cm; diameter: 2 cm) of silica gel (0.2-0.063 mm)
  8. washeluting with a mixture (80:20 by volume) (500 cc) of cyclohexane and ethyl acetate
  9. customcollecting 30-cc fractions
  10. concentrationThe combined fractions 5 to 11 are concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C
  11. dissolutionThe viscous yellow residue (2.4 g) is dissolved in isopropyl ether (15 cc)
  12. temperatureunder reflux
  13. temperatureThe solution is cooled
  14. customThe crystals formed
  15. washwashed with isopropyl ether (2 cc)
  16. customdried under reduced pressure (5 mm Hg; 0.68 kPa) at 40° C

Sources & evidence

ORD record
ord-4a7ee1bfb61941b794fb2f32d9eba35d
Source dataset
uspto-grants-1991_01
Patent number
US04985419

Reaction notes

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