Thionyl Chloride → N-Cyclopentylmethyl 10-[(2RS)-1-(1-pyrrolidinyl)-2-propyl]-2-phenothiazinecarboxamide

HRID 704234Notes

Reaction equation

HRID 704234 reaction equation
S(Cl)(Cl)=O.Cl.[N:6]1([CH2:11][CH:12]([N:14]2[C:27]3[CH:26]=[C:25]([C:28](O)=[O:29])[CH:24]=[CH:23][C:22]=3[S:21][C:20]3[C:15]2=[CH:16][CH:17]=[CH:18][CH:19]=3)[CH3:13])[CH2:10][CH2:9][CH2:8][CH2:7]1.[CH:31]1([CH2:36][NH2:37])[CH2:35][CH2:34][CH2:33][CH2:32]1.C(=O)(O)[O-].[Na+]>C(Cl)Cl.C(#N)C>[CH:31]1([CH2:36][NH:37][C:28]([C:25]2[CH:24]=[CH:23][C:22]3[S:21][C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[N:14]([CH:12]([CH3:13])[CH2:11][N:6]4[CH2:10][CH2:9][CH2:8][CH2:7]4)[C:27]=3[CH:26]=2)=[O:29])[CH2:35][CH2:34][CH2:33][CH2:32]1

Participants

7

Reactant 4

HCID 24386Thionyl ChlorideHCID 80153CyclopentanemethylamineHCID 516892Sodium BicarbonateHCID 1453664010-[1-(1-Pyrrolidinyl)-2-propyl]-2-phenothiazinecarboxylic acid hydrochloride

Product 1

HCID 15925377N-Cyclopentylmethyl 10-[(2RS)-1-(1-pyrrolidinyl)-2-propyl]-2-phenothiazinecarboxamideYield 72.9%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
15 °C

Procedure

Thionyl chloride (2 cc) is added to a suspension, cooled to 5° C., of 10-[(2RS)-1-(1-pyrrolidinyl)-2-propyl]-2-phenothiazinecarboxylic acid hydrochloride (1.6 g) in methylene chloride (50 cc). The suspension is stirred for 3 hours at 15° C. and then concentrated to dryness at 30° C. under reduced pressure (30 mm Hg; 4 kPa) to give a yellow residue which is taken up in methylene chloride (50 cc) at 5° C. Cyclopentylmethylamine (1.1 g) is added and the mixture is stirred for 12 hours at 25° C., and saturated sodium bicarbonate solution (150 cc) is then added. The mixture is extracted with ethyl acetate (2×100 cc). The organic phase is washed successively with distilled water (100 cc) and with brine (100 cc), dried over magnesium sulphate, filtered and concentrated to dryness at 40° C. under reduced pressure (30 mm Hg; 4 kPa). The yellow solid obtained (1.6 g) is dissolved in boiling acetonitrile (30 cc) and the solution is filtered. The filtrate is primed by scratching and then cooled with stirring for 1 hour. The solid is separated off by filtration, washed with acetonitrile (2×2 cc) and dried at 40° C. under reduced pressure (1 mm Hg; 0.13 kPa). N-Cyclopentylmethyl 10-[(2RS)-1-(1-pyrrolidinyl)-2-propyl]-2-phenothiazinecarboxamide (1.3 g) is obtained in the form of white crystals, m.p. 124° C. 1 Proton NMR (250 MHz, CDCl3, δ in ppm, J in Hz)

Workup

  1. concentrationconcentrated to dryness at 30° C. under reduced pressure (30 mm Hg; 4 kPa)
  2. customto give a yellow residue which
  3. stirringthe mixture is stirred for 12 hours at 25° C.
  4. extractionThe mixture is extracted with ethyl acetate (2×100 cc)
  5. washThe organic phase is washed successively with distilled water (100 cc) and with brine (100 cc)
  6. dry with materialdried over magnesium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated to dryness at 40° C. under reduced pressure (30 mm Hg; 4 kPa)
  9. customThe yellow solid obtained (1.6 g)
  10. dissolutionis dissolved
  11. filtrationthe solution is filtered
  12. temperaturecooled
  13. stirringwith stirring for 1 hour
  14. customThe solid is separated off by filtration
  15. washwashed with acetonitrile (2×2 cc)
  16. customdried at 40° C. under reduced pressure (1 mm Hg; 0.13 kPa)

Sources & evidence

ORD record
ord-d5d0645fff8c41eca89b25fcec04944e
Source dataset
uspto-grants-1991_01
Patent number
US04985419

Reaction notes

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