Hydrogen Sulfide → 7-chloro-10-[(2RS)-1-(1-pyrrolidinyl)-2-propyl]-2-phenothiazinecarbothioamide

HRID 704223Notes

Reaction equation

HRID 704223 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][CH:15]=1)[N:12]([CH:16]([CH3:23])[CH2:17][N:18]1[CH2:22][CH2:21][CH2:20][CH2:19]1)[C:11]1[CH:10]=[C:9]([C:24]#[N:25])[CH:8]=[CH:7][C:6]=1[S:5]2.C(N(CC)CC)C.[SH2:33]>N1C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][CH:15]=1)[N:12]([CH:16]([CH3:23])[CH2:17][N:18]1[CH2:19][CH2:20][CH2:21][CH2:22]1)[C:11]1[CH:10]=[C:9]([C:24](=[S:33])[NH2:25])[CH:8]=[CH:7][C:6]=1[S:5]2

Participants

5

Reactant 3

HCID 402Hydrogen SulfideHCID 8471TriethylamineHCID 159253667-chloro-10-[(2RS)-1-(1-pyrrolidinyl)-2-propyl]-2-phenothiazinecarbonitrile

Product 1

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

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of 7-chloro-10-[(2RS)-1-(1-pyrrolidinyl)-2-propyl]-2-phenothiazinecarbonitrile (31.07 g) and triethylamine (11.8 cc) in anhydrous pyridine (300 cc) is saturated with hydrogen sulphide for 4 hours at 25° C. The clear solution obtained is kept stirred for 12 hours at 25° C. The mixture is outgassed by bubbling nitrogen through for 2 hours, then diluted with ethyl acetate (250 cc) and washed with distilled water (5×200 cc). The organic phase is dried over magnesium sulphate and filtered, and the filtrate is concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa). The residue is purified by chromatography on a column (height: 38 cm; diameter: 6.5 cm) of silica gel (0.06-0.2 mm), eluting with a mixture of cyclohexane and ethyl acetate in proportions (by volume) of 70:30 (6 liters), 50:50 (4 liters) and 30:70 (4 liters), then with pure ethyl acetate (2 liters) and finally with a 90:10 mixture (6 liters) of ethyl acetate and methanol, collecting 50-cc fractions. The first 13.3 liters are discarded and fractions 6 to 94 are combined and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 50° C. to give 7-chloro-10-[(2RS)-1-(1-pyrrolidinyl)-2-propyl]-2-phenothiazinethiocarboxamide (21.43 g).

Workup

  1. customThe clear solution obtained
  2. customby bubbling nitrogen through for 2 hours
  3. additiondiluted with ethyl acetate (250 cc)
  4. washwashed with distilled water (5×200 cc)
  5. dry with materialThe organic phase is dried over magnesium sulphate
  6. filtrationfiltered
  7. concentrationthe filtrate is concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa)
  8. customThe residue is purified by chromatography on a column (height: 38 cm; diameter: 6.5 cm) of silica gel (0.06-0.2 mm)
  9. washeluting with a mixture of cyclohexane and ethyl acetate in proportions (by volume) of 70:30 (6 liters), 50:50 (4 liters) and 30:70 (4 liters)
  10. customwith pure ethyl acetate (2 liters) and finally with a 90:10 mixture (6 liters) of ethyl acetate and methanol, collecting 50-cc fractions
  11. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 50° C.

Sources & evidence

ORD record
ord-3fa95a64043943ddbed36d437e1cce21
Source dataset
uspto-grants-1991_01
Patent number
US04985419

Reaction notes

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