Methylamine → 10-[(2RS)-1-diethylamino-2-propyl]-N-methyl-2-phenothiazinecarbothioamide

HRID 704164Notes

Reaction equation

HRID 704164 reaction equation
CN.[CH2:3]([N:5]([CH2:26][CH3:27])[CH2:6][CH:7]([N:9]1[C:22]2[CH:21]=[C:20]([C:23](=[S:25])[NH2:24])[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])[CH3:4].[C:28](O)(=O)/C=C/C(O)=O>C(O)C>[CH2:26]([N:5]([CH2:3][CH3:4])[CH2:6][CH:7]([N:9]1[C:22]2[CH:21]=[C:20]([C:23](=[S:25])[NH:24][CH3:28])[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])[CH3:27]

Participants

5

Reactant 3

HCID 6329MethylamineHCID 444972Fumaric AcidHCID 1453651110-(1-Diethylamino-2-propyl)-2-phenothiazinecarbothioamide

Product 1

HCID 1592523610-[(2RS)-1-diethylamino-2-propyl]-N-methyl-2-phenothiazinecarbothioamideYield 88.8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent3×

Conditions

Temperature
60 °C

Procedure

A mixture of a 33% strength solution (10 cc) of methylamine in absolute ethanol and 10-[(2RS)-1-diethylamino-2-propyl]-2-phenothiazinecarbothioamide (2 g) in absolute ethanol (15 cc) is brought for 24 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 residue is taken up with ethyl acetate (100° C.), washed with distilled water (2×50 cc), dried over magnesium sulphate in the presence of charcoal 3S, filtered and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C. The residual orange oil (1.7 g) is purified by chromatography on a column (height: 25 cm; diameter: 2.5 cm) of silica gel (0.04-0.063 mm) with a slight excess pressure of nitrogen (40 kPa), eluting successively with ethyl acetate (750 cc) and with a mixture (90:10 by volume) (500 cc) cf ethyl acetate and ethanol and collecting 50-cc fractions. Fractions 2 to 7 are combined and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C. The residual brown oil (1.3 g) is dissolved at 50° C. in ethanol (3 cc) and the solution obtained is poured into a solution of fumaric acid (0.39 g) in ethanol (3 cc), with stirring and at a temperature in the region of 60° C. After 1 hour with stirring at a temperature in the region of 5° C., the solid formed is drained, washed with ethanol (3×1 cc) and dried in the air. This solid is redissolved in ethanol (20 cc) under reflux and then stored for 1 hour at a temperature in the region of 5° C. The solid formed is drained, washed with ethanol (3×1 cc) and dried under reduced pressure (5 mm Hg; 0.68 kPa) at 40° C. 10-[(2RS)-1-diethylamino-2-propyl]-N-methyl-2-phenothiazinecarbothioamide acid fumarate (1.15 g) is thereby obtained in the form of a yellow solid, m.p. 224° C.;

Workup

  1. temperatureAfter cooling
  2. concentrationthe mixture is concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C
  3. customis taken up with ethyl acetate (100° C.)
  4. washwashed with distilled water (2×50 cc)
  5. dry with materialdried over magnesium sulphate in the presence of charcoal 3S
  6. filtrationfiltered
  7. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C
  8. customThe residual orange oil (1.7 g) is purified by chromatography on a column (height: 25 cm; diameter: 2.5 cm) of silica gel (0.04-0.063 mm) with a slight excess pressure of nitrogen (40 kPa)
  9. washeluting successively with ethyl acetate (750 cc) and with a mixture (90:10 by volume) (500 cc) cf ethyl acetate and ethanol
  10. customcollecting 50-cc fractions
  11. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C
  12. dissolutionThe residual brown oil (1.3 g) is dissolved at 50° C. in ethanol (3 cc)
  13. customthe solution obtained
  14. stirringAfter 1 hour with stirring at a temperature in the region of 5° C.
  15. customthe solid formed
  16. washwashed with ethanol (3×1 cc)
  17. customdried in the air
  18. dissolutionThis solid is redissolved in ethanol (20 cc)
  19. temperatureunder reflux
  20. waitstored for 1 hour at a temperature in the region of 5° C
  21. customThe solid formed
  22. washwashed with ethanol (3×1 cc)
  23. customdried under reduced pressure (5 mm Hg; 0.68 kPa) at 40° C

Sources & evidence

ORD record
ord-d2b24ece64344d0d804374dc703cd92a
Source dataset
uspto-grants-1991_01
Patent number
US04985419

Reaction notes

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