(2S)-2-(4-Methoxybutyl)piperazine → (S)-10-[3-(4-methoxybutyl)-piperazin-1-yl]-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulene

HRID 131442Notes

Reaction equation

HRID 131442 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][CH2:5][CH2:6][C@H:7]1[CH2:12][NH:11][CH2:10][CH2:9][NH:8]1.[CH3:13][C:14]1[S:23][C:22]2[NH:21][C:20]3[CH:24]=[CH:25][CH:26]=[CH:27][C:19]=3[N:18]=[C:17](N)[C:16]=2[CH:15]=1>CN1C(=O)CCC1.[Cl-].[Na+].O>[CH3:1][O:2][CH2:3][CH2:4][CH2:5][CH2:6][C@@H:7]1[NH:8][CH2:9][CH2:10][N:11]([C:17]2[C:16]3[CH:15]=[C:14]([CH3:13])[S:23][C:22]=3[NH:21][C:20]3[CH:24]=[CH:25][CH:26]=[CH:27][C:19]=3[N:18]=2)[CH2:12]1

Participants

5

Reactant 2

HCID 45099588(2S)-2-(4-Methoxybutyl)piperazineHCID 135446208Olanzamine

Product 1

HCID 135430626(S)-10-[3-(4-methoxybutyl)-piperazin-1-yl]-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulene

Reagents, catalysts & solvents 2

HCID 13387N-methyl-2-pyrrolidoneSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
211 °C

Procedure

Heat in a 211° C. oil bath, a stirring solution of (S)-2-(4-methoxybutyl)-piperazine 0.086 g, 0.49 mmol), and 2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulen-10-ylamine (0.114 g, 0.49 mmol) in NMP (1 mL) for 4 h. Cool to room temperature, dilute the solution with brine (15 mL) and extract with EtOAc (3×30 mL). Concentrate the organic layers under reduced pressure to a volume of 20 mL and wash with 75% brine (4×20 mL). Dry the organic layer over Na2SO4, and filter. Concentrate the mixture under reduced pressure and purify by silica gel chromatography eluting with 10% (33% 2 M NH3 in MeOH/64% EtOH)/CH2Cl2. Combine the purified fractions, concentrate under reduced pressure, azeotrope with CH2Cl2/hexanes and place under vacuum to give the title compound: brown solid (0.036 g), mass spectrum (m/e):385.08 (M+H).

Workup

  1. temperatureCool to room temperature
  2. extractionextract with EtOAc (3×30 mL)
  3. concentrationConcentrate the organic layers under reduced pressure to a volume of 20 mL
  4. washwash with 75% brine (4×20 mL)
  5. dry with materialDry the organic layer over Na2SO4
  6. filtrationfilter
  7. concentrationConcentrate the mixture under reduced pressure
  8. custompurify by silica gel chromatography
  9. washeluting with 10% (33% 2 M NH3 in MeOH/64% EtOH)/CH2Cl2
  10. concentrationconcentrate under reduced pressure, azeotrope with CH2Cl2/hexanes and place under vacuum

Sources & evidence

ORD record
ord-c2c53554257c4f2dad172fe3d98ccc06
Source dataset
uspto-grants-2008_06
Patent number
US07384934B2

Reaction notes

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