(S)-2-(2-Methoxyethyl)piperazine → (S)-6,7-Difluoro-10-[3-(2-methoxy-ethyl)-piperazin-1-yl]-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulene

HRID 131452

Reaction equation

HRID 131452 reaction equation
Cl.[F:2][C:3]1[C:4]([F:19])=[CH:5][C:6]2[N:15]=[C:14]([NH2:16])[C:13]3[CH:12]=[C:11]([CH3:17])[S:10][C:9]=3[NH:8][C:7]=2[CH:18]=1.[CH3:20][O:21][CH2:22][CH2:23][C@H:24]1[CH2:29]N[CH2:27][CH2:26][NH:25]1>CS(C)=O.C1(C)C=CC=CC=1.O.C(OCC)(=O)C>[F:2][C:3]1[C:4]([F:19])=[CH:5][C:6]2[N:15]=[C:14]([N:16]3[CH2:27][CH2:26][NH:25][C@@H:24]([CH2:23][CH2:22][O:21][CH3:20])[CH2:29]3)[C:13]3[CH:12]=[C:11]([CH3:17])[S:10][C:9]=3[NH:8][C:7]=2[CH:18]=1

Participants

6

Reactant 2

HCID 55287560(S)-2-(2-Methoxyethyl)piperazineHCID 1363885776,7-Difluoro-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulen-10-ylamine hydrochloride

Product 1

HCID 135434034(S)-6,7-Difluoro-10-[3-(2-methoxy-ethyl)-piperazin-1-yl]-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azuleneYield 38%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 22340214Dimethylsulfoxide tolueneSolvent

Conditions

Temperature
130 °C

Procedure

Dissolve 6,7-difluoro-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulen-10-ylamine hydrochloride (1.7 g, 5.66 mmol) and (S)-2-(2-methoxy-ethyl)-piperazine (2.45 g, 17.0 mmol) in dimethylsulfoxide/toluene (1:2)(21 ml), stir under nitrogen and heat in an oil bath at 130° C. for 43 hours. Cool to ambient temperature. Dilute the mixture with one volume water and two volumes ethyl acetate, separate layers and extract the aqueous layer with ethyl acetate. Basify the aqueous layer with ammonium hydroxide and extract with ethyl acetate. Combine all ethyl acetate extracts and wash with water and brine. Dry the organic phase (Na2SO4), filter and concentrate under reduced pressure. Purify by silica gel chromatography (eluent: 0-10% 2N ammonia in methanol/dichloromethane) to give the title compound (840 mg, 38%): Mass Spectrum (ESMS) 393 (M+1); 391 (M−1).

Workup

  1. temperatureCool to ambient temperature
  2. customseparate layers
  3. extractionextract the aqueous layer with ethyl acetate
  4. extractionextract with ethyl acetate
  5. washwash with water and brine
  6. dry with materialDry the organic phase (Na2SO4)
  7. filtrationfilter
  8. concentrationconcentrate under reduced pressure
  9. customPurify by silica gel chromatography (eluent: 0-10% 2N ammonia in methanol/dichloromethane)

Sources & evidence

ORD record
ord-bfd5740c595d4999a47808bba67d417e
Source dataset
uspto-grants-2008_06
Patent number
US07384934B2

Linked notes

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