N-methyl-2-pyrrolidone → (S)-10-{3-[2-(4-Methoxy-phenyl)-ethyl]-piperazin-1-yl}-2-methyl-4H-3-thia-1,4,9-triaza-benzo[f]azulene

HRID 1350455Notes

Reaction equation

HRID 1350455 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][C@H:11]2[CH2:16][NH:15][CH2:14][CH2:13][NH:12]2)=[CH:5][CH:4]=1.[CH3:17][C:18]1[S:27][C:26]2[NH:25][C:24]3[CH:28]=[CH:29][CH:30]=[CH:31][C:23]=3[N:22]=[C:21](N)[C:20]=2[N:19]=1.CN1CCCC1=O>C(OCC)(=O)C.O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:9][CH2:10][C@@H:11]2[NH:12][CH2:13][CH2:14][N:15]([C:21]3[C:20]4[N:19]=[C:18]([CH3:17])[S:27][C:26]=4[NH:25][C:24]4[CH:28]=[CH:29][CH:30]=[CH:31][C:23]=4[N:22]=3)[CH2:16]2)=[CH:7][CH:8]=1

Participants

6

Reactant 3

HCID 13387N-methyl-2-pyrrolidoneHCID 21093530HCID 21093530, compoundHCID 1357977442-methyl-4H-3-thia-1,4,9-triazabenzo[f]azulene-10-ylamine

Product 1

HCID 136005561(S)-10-{3-[2-(4-Methoxy-phenyl)-ethyl]-piperazin-1-yl}-2-methyl-4H-3-thia-1,4,9-triaza-benzo[f]azuleneYield 109.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
195 °C

Procedure

Combine (S)-2-[2-(4-methoxy-phenyl)-ethyl]-piperazine (180 mg, 0.82 mmol), 2-methyl-4H-3-thia-1,4,9-triaza-benzo[f]azulen-10-ylamine (188 mg, 0.82 mmol), 1-methyl-2-pyrrolidinone (5 mL). Heat at 195° C. After 3.75 h, cool to ambient temperature and stir 18 h. Combine with another 2.30 mmol reaction executed under same conditions. Dilute with ethyl acetate and water. Extract with ethyl acetate. Wash the extracts with water and brine, dry over sodium sulfate, filter and concentrate the filtrate. Purify by silica gel chromatography using 2N ammonia in methanol-methylene chloride (2.5%–4%) as the eluent to give 388 mg (29%) of the title compound: mass spectrum (ion spray): m/z=434 (M+1), 432 (M−1). HR-MS calculated for C24H28N5OS: 434.2015. Found 434.201 HPLC: Symmetry C18 column (3.5 μm, 4.6×50 mm). Gradient 5% to 90% solvent B in 7 min. Solvent A was 0.1% (v/v) TFA in water and solvent B was acetonitrile. Retention time 5.4 min; 100% pure.

Workup

  1. temperaturecool to ambient temperature
  2. customCombine with another 2.30 mmol reaction
  3. extractionExtract with ethyl acetate
  4. washWash the extracts with water and brine
  5. dry with materialdry over sodium sulfate
  6. filtrationfilter
  7. concentrationconcentrate the filtrate
  8. customPurify by silica gel chromatography

Sources & evidence

ORD record
ord-0f31fc04ad8b46888d540b59683f06f7
Source dataset
uspto-grants-2007_05
Patent number
US07214673B2

Reaction notes

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