Hydrogen Sulfide → HCID 15925280, compound

HRID 704187Notes

Reaction equation

HRID 704187 reaction equation
[CH3:1][CH:2]1[CH2:7][CH2:6][CH2:5][N:4]([CH2:8][CH:9]([N:11]2[C:24]3[CH:23]=[C:22]([C:25](=[S:27])[NH2:26])[CH:21]=[CH:20][C:19]=3[S:18][C:17]3[C:12]2=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH3:10])[CH2:3]1.[CH2:28](N)[CH2:29][CH3:30].S>C(O)C>[CH3:1][CH:2]1[CH2:7][CH2:6][CH2:5][N:4]([CH2:8][CH:9]([N:11]2[C:24]3[CH:23]=[C:22]([C:25](=[S:27])[NH:26][CH2:28][CH2:29][CH3:30])[CH:21]=[CH:20][C:19]=3[S:18][C:17]3[C:12]2=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH3:10])[CH2:3]1

Participants

5

Reactant 3

HCID 402Hydrogen SulfideHCID 7852PropylamineHCID 15925278HCID 15925278, compound

Product 1

HCID 15925280HCID 15925280, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 10-{(2RS)-1-[(3RS)-3-methyl-1-piperidyl]-2-propyl}-2-phenothiazinecarbothioamide acid fumarate (1 g) and propylamine (2.5 cc) in absolute ethanol (20 cc) is saturated with hydrogen sulphide and heated for 16 hours to a temperature in the region of 100° C. After cooling, the mixture is concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C. The residual orange oil (1.5 g) is purified by chromatography on a column (height: 25 cm; diameter: 2 cm) of silica gel (0.04-0.063 mm) with a slight excess pressure of nitrogen (40 kPa), eluting with a mixture (80:20 by volume) (250 cc) of ethyl acetate and cyclohexane and collecting 40-cc fractions. The combined fractions 3 and 4 are concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C. The residual yellow oil (0.9 g) is dissolved in ethanol (3 cc) at 60° C., and this hot solution is poured, with stirring, into a solution of fumaric acid (0.23 g) in ethanol (3.5 cc) under reflux. After cooling, stirring is continued for 2 hours at a temperature in the region of 5° C. The solid formed is drained, washed with ethanol (2×1 cc) and dried under reduced pressure (5 mm Hg; 0.68 kPa) at 40° C. 10-{(2RS}-1-[(3RS)-3-Methyl-1-piperidyl]-2-propyl}-N-propyl-2-phenothiazinecarbothioamide neutral fumarate (0.53 g) is thereby obtained in the form of a yellow solid, m.p. 126° C.

Workup

  1. temperatureAfter cooling
  2. concentrationthe mixture is concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C
  3. customThe residual orange oil (1.5 g) is purified by chromatography on a column (height: 25 cm; diameter: 2 cm) of silica gel (0.04-0.063 mm) with a slight excess pressure of nitrogen (40 kPa)
  4. washeluting with a mixture (80:20 by volume) (250 cc) of ethyl acetate and cyclohexane
  5. customcollecting 40-cc fractions
  6. concentrationThe combined fractions 3 and 4 are concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C
  7. dissolutionThe residual yellow oil (0.9 g) is dissolved in ethanol (3 cc) at 60° C.
  8. additionthis hot solution is poured
  9. temperatureunder reflux
  10. temperatureAfter cooling
  11. stirringstirring
  12. customThe solid formed
  13. washwashed with ethanol (2×1 cc)
  14. customdried under reduced pressure (5 mm Hg; 0.68 kPa) at 40° C

Sources & evidence

ORD record
ord-013f83f1d3a94416b3f50bf859ded4d7
Source dataset
uspto-grants-1991_01
Patent number
US04985419

Reaction notes

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