Water → N-propyl-10-[1-(1-pyrrolidinyl)-2-propyl]-2-phenothiazinecarboxamide

HRID 1109528Notes

Reaction equation

HRID 1109528 reaction equation
[C:1](O)(=O)/[CH:2]=[CH:3]/[C:4](O)=O.[CH:9]1[C:22]2[NH:21][C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[S:14][C:13]=2[CH:12]=[CH:11][C:10]=1[C:23](=S)[NH2:24].[OH2:26]>C(O)C>[CH2:10]([NH:24][C:23]([C:10]1[CH:11]=[CH:12][C:13]2[S:14][C:15]3[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=3)[N:21]([CH:19]([CH3:18])[CH2:20][N:21]3[CH2:4][CH2:3][CH2:2][CH2:1]3)[C:22]=2[CH:9]=1)=[O:26])[CH2:9][CH3:22]

Participants

5

Reactant 3

HCID 962WaterHCID 444972Fumaric AcidHCID 2271158710H-phenothiazine-2-carbothioamide

Product 1

HCID 9800851N-propyl-10-[1-(1-pyrrolidinyl)-2-propyl]-2-phenothiazinecarboxamide

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
20 °C

Procedure

Fumaric acid (2.7 g) is added to a solution of N-propyl-10-[1-pyrrolidinyl)-2-propyl]-2-phenothiazinecarbothioamide, L series (9.5 g), in ethanol (100 cc). The solution obtained is concentrated to dryness under reduced pressure (300 mm Hg; 4 kPa) at 40° C. The meringue-like yellow residue is taken up with acetic acid (200 cc). Mercuric acetate (7.3 g) is added to the solution obtained and the mixture is stirred for 16 hours at a temperature in the region of 20° C. The black suspension obtained is diluted with distilled water (200 cc) and filtered. The yellow filtrate is concentrated under reduced pressure (30 mm Hg; 4 kPa) at 40° C. The residue is taken up with ethyl acetate (250 cc) and distilled water (50 cc) and then treated with sodium hydroxide (d=1.33) to pH 13. The aqueous phase is separated after settling has taken place and extracted with ethyl acetate (250 cc). The organic phases are combined, washed successively with distilled water (2×100 cc) and with a saturated aqueous sodium chloride solution (100 cc) and dried over magnesium sulphate. After filtration, the yellow filtrate is concentrated under reduced pressure (30 mm Hg; 4 kPa) at 40° C. and a crude yellow oil (9.2 g) is thereby obtained. This residue is purified by chromatography on a column (height: 22 cm; diameter: 4 cm) of silica gel (0.2-0.063 mm), eluting with a mixture of methylene chloride and methanol (95:5 by volume). The first 1500 cc are discarded and the next 1500 cc are concentrated under reduced pressure (30 mm Hg; 4 kPa) at 40° C. to give N-propyl-10-[1-(pyrrolidinyl)-2-propyl]-2-phenothiazinecarboxamide, L series (7.3 g), in the form of a yellow gum.

Workup

  1. customThe solution obtained
  2. concentrationis concentrated to dryness under reduced pressure (300 mm Hg; 4 kPa) at 40° C
  3. additionMercuric acetate (7.3 g) is added to the solution
  4. customobtained
  5. customThe black suspension obtained
  6. filtrationfiltered
  7. concentrationThe yellow filtrate is concentrated under reduced pressure (30 mm Hg; 4 kPa) at 40° C
  8. distillationdistilled water (50 cc)
  9. additiontreated with sodium hydroxide (d=1.33) to pH 13
  10. customThe aqueous phase is separated after settling
  11. extractionextracted with ethyl acetate (250 cc)
  12. washwashed successively with distilled water (2×100 cc) and with a saturated aqueous sodium chloride solution (100 cc)
  13. dry with materialdried over magnesium sulphate
  14. filtrationAfter filtration
  15. concentrationthe yellow filtrate is concentrated under reduced pressure (30 mm Hg; 4 kPa) at 40° C.
  16. customa crude yellow oil (9.2 g) is thereby obtained
  17. customThis residue is purified by chromatography on a column (height: 22 cm; diameter: 4 cm) of silica gel (0.2-0.063 mm)
  18. washeluting with a mixture of methylene chloride and methanol (95:5 by volume)
  19. concentrationthe next 1500 cc are concentrated under reduced pressure (30 mm Hg; 4 kPa) at 40° C.

Sources & evidence

ORD record
ord-d5a2101ab8d44965ab2e56755ef3c442
Source dataset
uspto-grants-1994_06
Patent number
US05321026

Reaction notes

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