Hydrogen Sulfide → HCID 54318968, compound

HRID 704230Notes

Reaction equation

HRID 704230 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][CH2:5][CH2:4][CH:3]1[NH2:8].S.[OH:10][CH2:11][C@H:12]1[CH2:16][CH2:15][CH2:14][N:13]1[CH2:17][CH:18]([N:20]1[C:33]2[CH:32]=[C:31]([C:34](=S)N)[CH:30]=[CH:29][C:28]=2[S:27][C:26]2[C:21]1=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH3:19].C(OC(C)C)(C)C>C(OCC)(=O)C>[NH:1]1[CH:2]2[CH2:7][CH2:6][CH2:5][CH2:4][CH:3]2[N:8]=[C:34]1[C:31]1[CH:30]=[CH:29][C:28]2[S:27][C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[N:20]([CH:18]([CH3:19])[CH2:17][N:13]3[CH2:14][CH2:15][CH2:16][C@@H:12]3[CH2:11][OH:10])[C:33]=2[CH:32]=1

Participants

6

Reactant 4

HCID 402Hydrogen SulfideHCID 46101,2-DiaminocyclohexaneHCID 7914Diisopropyl EtherHCID 54075963HCID 54075963, compound

Product 1

HCID 54318968HCID 54318968, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

1,2-Diaminocyclohexane (7.98 g) is added to an ethanolic solution (30 cc), saturated with hydrogen sulphide, of 10-{1-[(2R)-2-hydroxymethyl-1-pyrrolidinyl]-2-propyl}-2-phenothiazinecarbothioamide, L series (2.79 g). The mixture is heated in an autoclave at 150° C. for 17 hours, then diluted with ethyl acetate (250 cc) and washed with distilled water (4×200 cc). The organic phase is separated after settling has taken place, dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C. The residue is stirred with boiling acetonitrile (6×30 cc), and the oil obtained is solidified by stirring with isopropyl ether (100 cc). The residue is chromatographed on a column (height: 52 cm; diameter: 2.5 cm) of silica gel (0.2-0.06 mm), eluting with a 60:40 (by volume) mixture (2 liters) of 1,2-dichloroethane and methanol and collecting 120-cc fractions. The first liter is discarded, and fractions 4 to 7 containing the pure product are combined and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C. to give 2-(3a,4,5,6,7,7a-hexahydro-1H-benzimidazol-2-yl)-10-{1-[(2R)-2-hydroxymethyl-1-pyrrolidinyl]-2-propyl}phenothiazine, L series (1.8 g) in the form of a yellow solid.

Workup

  1. washwashed with distilled water (4×200 cc)
  2. customThe organic phase is separated after settling
  3. dry with materialdried over magnesium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C
  6. customthe oil obtained
  7. customThe residue is chromatographed on a column (height: 52 cm; diameter: 2.5 cm) of silica gel (0.2-0.06 mm)
  8. washeluting with a 60:40 (by volume) mixture (2 liters) of 1,2-dichloroethane and methanol
  9. customcollecting 120-cc fractions
  10. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C.

Sources & evidence

ORD record
ord-1aa663edb88346ccb6b4b293a559d169
Source dataset
uspto-grants-1991_01
Patent number
US04985419

Reaction notes

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