Hydrogen Sulfide → HCID 54252607, compound

HRID 704202Notes

Reaction equation

HRID 704202 reaction equation
[CH3:1][CH:2]([CH3:6])[CH2:3][CH2:4]N.[OH:7][CH2:8][C@H:9]1[CH2:13][CH2:12][CH2:11][N:10]1[CH2:14][CH:15]([N:17]1[C:30]2[CH:29]=[C:28]([C:31](=[S:33])[NH2:32])[CH:27]=[CH:26][C:25]=2[S:24][C:23]2[C:18]1=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH3:16].S>C(O)C.C(OC(C)C)(C)C>[OH:7][CH2:8][C@H:9]1[CH2:13][CH2:12][CH2:11][N:10]1[CH2:14][CH:15]([N:17]1[C:30]2[CH:29]=[C:28]([C:31](=[S:33])[NH:32][CH2:4][CH2:3][CH:2]([CH3:6])[CH3:1])[CH:27]=[CH:26][C:25]=2[S:24][C:23]2[C:18]1=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH3:16]

Participants

6

Reactant 3

HCID 402Hydrogen SulfideHCID 7894IsoamylamineHCID 54075963HCID 54075963, compound

Product 1

HCID 54252607HCID 54252607, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 7914Diisopropyl EtherSolvent

Conditions

Temperature
25 °C

Procedure

3-Methylbutylamine (8.5 cc) is added to a solution of 10-{1-[(2R)-2-hydroxymethyl-1-pyrrolidinyl]-2-propyl}-2-phenothiazinecarbothioamide, L series (5.86 g) in absolute ethanol (135 cc). The mixture is saturated with hydrogen sulphide and then brought to 150° C. for 16 hours. The reaction mixture is concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 50° C. The residue is diluted with ethyl acetate (150 cc), washed with distilled water (3×100 cc) and with saturated sodium chloride solution (100 cc), dried over magnesium sulphate and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 50° C. before being purified by chromatography on a column (height: 32 cm; diameter: 4 cm) of silica gel (0.06-0.2 mm), eluting with pure ethyl acetate (1000 cc), collecting 60-cc fractions. Fractions 6 to 12 are combined and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) to give a residue which is dissolved in isopropyl ether (80 cc). Crystallization is primed by scratching, and the mixture is stirred for 12 hours at 25° C. The crystals are filtered off to give 10-{1-[(2R)-2-hydroxymethyl-1-pyrrolidinyl]-2-propyl}-N-(3-methylbutyl)-2-phenothiazinecarbothioamide, L series (4.3 g) in the form of yellow crystals, m.p. 140° C.

Workup

  1. concentrationThe reaction mixture is concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 50° C
  2. additionThe residue is diluted with ethyl acetate (150 cc)
  3. washwashed with distilled water (3×100 cc) and with saturated sodium chloride solution (100 cc)
  4. dry with materialdried over magnesium sulphate
  5. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 50° C.
  6. custombefore being purified by chromatography on a column (height: 32 cm; diameter: 4 cm) of silica gel (0.06-0.2 mm)
  7. washeluting with pure ethyl acetate (1000 cc)
  8. customcollecting 60-cc fractions
  9. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa)
  10. customto give a residue which
  11. customCrystallization
  12. filtrationThe crystals are filtered off

Sources & evidence

ORD record
ord-76cde137c25d4d9298e03fb4b27471d7
Source dataset
uspto-grants-1991_01
Patent number
US04985419

Reaction notes

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