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 1350455노트

반응식

HRID 1350455 반응식
[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

참가 물질

6

반응물 3

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

생성물 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]azulene수율 109.1%

시약·촉매·용매 2

HCID 962Water용매HCID 8857Ethyl Acetate용매

반응 조건

온도
195 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-0f31fc04ad8b46888d540b59683f06f7
출처 데이터셋
uspto-grants-2007_05
특허 번호
US07214673B2

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