Diisopropylethylamine → (S)-5-[3-(2-Methoxy-ethyl)-piperazin-1-yl]-8-trifluoromethyl-11H-12-thia-6,11-diaza-dibenzo[a,f]azulene

HRID 131513

Reaction equation

HRID 131513 reaction equation
Cl.[F:2][C:3]([F:24])([F:23])[C:4]1[CH:22]=[CH:21][C:7]2[NH:8][C:9]3[S:10][C:11]4[CH:20]=[CH:19][CH:18]=[CH:17][C:12]=4[C:13]=3[C:14]([NH2:16])=[N:15][C:6]=2[CH:5]=1.[CH3:25][O:26][CH2:27][CH2:28][C@H:29]1[CH2:34]N[CH2:32][CH2:31][NH:30]1.C(N(C(C)C)CC)(C)C>CS(C)=O.C1(C)C=CC=CC=1.C(OCC)(=O)C.[OH-].[Na+]>[CH3:25][O:26][CH2:27][CH2:28][C@@H:29]1[NH:30][CH2:31][CH2:32][N:16]([C:14]2[C:13]3[C:12]4[CH:17]=[CH:18][CH:19]=[CH:20][C:11]=4[S:10][C:9]=3[NH:8][C:7]3[CH:21]=[CH:22][C:4]([C:3]([F:2])([F:23])[F:24])=[CH:5][C:6]=3[N:15]=2)[CH2:34]1

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 55287560(S)-2-(2-Methoxyethyl)piperazineHCID 1363885748-Trifluoromethyl-11H-12-thia-6,11-diaza-dibenzo[a,f]azulen-5-ylamine hydrochloride

Product 1

HCID 135507279(S)-5-[3-(2-Methoxy-ethyl)-piperazin-1-yl]-8-trifluoromethyl-11H-12-thia-6,11-diaza-dibenzo[a,f]azuleneYield 35.9%

Reagents, catalysts & solvents 3

HCID 8857Ethyl AcetateSolventHCID 14798Sodium HydroxideSolventHCID 22340214Dimethylsulfoxide tolueneSolvent

Procedure

Add 8-trifluoromethyl-11H-12-thia-6,11-diaza-dibenzo[a,f]azulen-5-ylamine hydrochloride (0.75 g, 2.0 mmol) to a solution of (S)-2-(2-methoxy-ethyl)-piperazine (0.58 g, 4.1 mmol) in dimethyl sulfoxide: toluene (1:8, 0.2M). Add diisopropylethylamine (1 equiv), heat to 110° C., and stir. After 45 hours, cool to ambient temperature, and dilute with ethyl acetate and 0.1 N NaOH. Separate the aqueous layer and extract it with ethyl acetate (3×). Wash all organics with a saturated solution of sodium chloride, and then dry (sodium sulfate), filter, and concentrate them under reduced pressure. Purify the oil by flash chromatography, eluting with a gradient of a 3% solution of 2M ammonia in methanol, in dichloromethane (0-100% in dichloromethane). Reconstitute the material in ethyl acetate and wash it with a saturated solution of sodium chloride (2×) to remove residual dimethylsulfoxide. Back extract the combined aqueous layers with ethyl acetate. Dry (sodium sulfate) the organic phases, filter, and concentrate them under reduced pressure to give the title compound (0.331 g). Mass spectrum (APCI+, m/e): 461 (M+1).

Workup

  1. customSeparate the aqueous layer
  2. extractionextract it with ethyl acetate (3×)
  3. washWash all organics with a saturated solution of sodium chloride
  4. dry with materialdry (sodium sulfate)
  5. filtrationfilter
  6. concentrationconcentrate them under reduced pressure
  7. customPurify the oil by flash chromatography
  8. washeluting with a gradient of a 3% solution of 2M ammonia in methanol, in dichloromethane (0-100% in dichloromethane)
  9. washwash it with a saturated solution of sodium chloride (2×)
  10. customto remove residual dimethylsulfoxide
  11. extractionBack extract the combined aqueous layers with ethyl acetate
  12. dry with materialDry (sodium sulfate) the organic phases
  13. filtrationfilter
  14. concentrationconcentrate them under reduced pressure

Sources & evidence

ORD record
ord-d115a17f1cc54945b2f705fac539b7de
Source dataset
uspto-grants-2008_06
Patent number
US07384934B2

Linked notes

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