1,2-Diaminocyclohexane → 7-chloro-2-(3a, 4, 5, 6, 7, 7a-hexahydro-1H-benzimidazol-2-yl)-10-[(2RS)-1-(1-pyrrolidinyl)-2-propyl]phenothiazine

HRID 704222Notes

Reaction equation

HRID 704222 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][CH2:5][CH2:4][CH:3]1[NH2:8].[Cl:9][C:10]1[CH:11]=[C:12]2[C:21](=[CH:22][CH:23]=1)[N:20]([CH:24]([CH3:31])[CH2:25][N:26]1[CH2:30][CH2:29][CH2:28][CH2:27]1)[C:19]1[CH:18]=[C:17]([C:32](=S)N)[CH:16]=[CH:15][C:14]=1[S:13]2>C(OCC)(=O)C>[Cl:9][C:10]1[CH:11]=[C:12]2[C:21](=[CH:22][CH:23]=1)[N:20]([CH:24]([CH3:31])[CH2:25][N:26]1[CH2:27][CH2:28][CH2:29][CH2:30]1)[C:19]1[CH:18]=[C:17]([C:32]3[NH:8][CH:3]4[CH2:4][CH2:5][CH2:6][CH2:7][CH:2]4[N:1]=3)[CH:16]=[CH:15][C:14]=1[S:13]2

Participants

4

Reactant 2

HCID 46101,2-DiaminocyclohexaneHCID 159253647-chloro-10-[(2RS)-1-(1-pyrrolidinyl)-2-propyl]-2-phenothiazinecarbothioamide

Product 1

HCID 159253657-chloro-2-(3a, 4, 5, 6, 7, 7a-hexahydro-1H-benzimidazol-2-yl)-10-[(2RS)-1-(1-pyrrolidinyl)-2-propyl]phenothiazine

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

1,2-Diaminocyclohexane (15.78 cc) is added to an ethanolic solution (70 cc) of 7-chloro-10-[(2RS)-1-(1-pyrrolidinyl)-2-propyl]-2-phenothiazinecarbothioamide (5.20 g). The mixture is heated in an autoclave to 150° C. for 17 hours. After cooling, the reaction mixture is diluted with ethyl acetate (250 cc) and washed with j distilled water (5×250 cc). The organic phase is extracted with normal hydrochloric acid solution (300 cc). After separation of the organic phase when settling has taken place, the acidic aqueous phase is alkalinized with concentrated caustic soda and extracted with ethyl acetate (200 cc). The organic phase is separated after settling has taken place, dried over magnesium sulpate, filtered and evaporated under reduced pressure (30 mm Hg; 4 kPa) at 40° C. The residue is chromatographed on a column (height: 52 cm; diameter: 2.5 cm) of silica gel (0.2-0.06 mm), eluting with pure ethyl acetate (2 liters) 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 7-chloro-2-(3a, 4, 5, 6, 7, 7a-hexahydro-1H-benzimidazol-2 -yl)-10-[(2RS)-1-(1-pyrrolidinyl)-2-propyl]phenothiazine (0.72 g) in the form of a yellow solid, m.p. 120° C.

Workup

  1. temperatureAfter cooling
  2. washwashed
  3. distillationwith j distilled water (5×250 cc)
  4. extractionThe organic phase is extracted with normal hydrochloric acid solution (300 cc)
  5. customAfter separation of the organic phase when
  6. extractionextracted with ethyl acetate (200 cc)
  7. customThe organic phase is separated after settling
  8. dry with materialdried over magnesium sulpate
  9. filtrationfiltered
  10. customevaporated under reduced pressure (30 mm Hg; 4 kPa) at 40° C
  11. customThe residue is chromatographed on a column (height: 52 cm; diameter: 2.5 cm) of silica gel (0.2-0.06 mm)
  12. washeluting with pure ethyl acetate (2 liters)
  13. customcollecting 120-cc fractions
  14. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C.

Sources & evidence

ORD record
ord-fa4c30458cc24129b7ddd4f8f351589c
Source dataset
uspto-grants-1991_01
Patent number
US04985419

Reaction notes

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