Acetic Acid → 9-Bromo-2-[2-(2,4-difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene

HRID 84651

반응식

HRID 84651 반응식
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[O:14][CH2:13][CH2:12][C:11]3[S:10][C:9]([C:15]([NH2:17])=O)=[N:8][C:7]=3[C:6]=2[CH:18]=1.[CH3:19]OC(OC)N(C)C.CC(O)=O.Cl.[F:32][C:33]1[CH:38]=[C:37]([F:39])[CH:36]=[CH:35][C:34]=1[NH:40][NH2:41]>C1(C)C=CC=CC=1.O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[O:14][CH2:13][CH2:12][C:11]3[S:10][C:9]([C:15]4[N:40]([C:34]5[CH:35]=[CH:36][C:37]([F:39])=[CH:38][C:33]=5[F:32])[N:41]=[CH:19][N:17]=4)=[N:8][C:7]=3[C:6]=2[CH:18]=1

참가 물질

7

반응물 4

HCID 176Acetic AcidHCID 78373Dimethylformamide dimethyl acetalHCID 27333012,4-Difluorophenylhydrazine hydrochlorideHCID 582039029-Bromo-4,5-dihydro-[1]benzoxepino[5,4-d]thiazole-2-carboxamide

생성물 1

HCID 532348939-Bromo-2-[2-(2,4-difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene수율 31%

시약·촉매·용매 2

HCID 962Water용매HCID 1140Toluene용매

반응 조건

온도
100 °C

실험 절차

A stirred suspension of 9-bromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid amide (0.70 g; 2.2 mmol) and dimethylformamide dimethylacetal (DMF·DMA, 6 ml) in toluene (5 ml) was heated at 100° C. overnight (16 h) upon which time the reaction mixture was concentrated. To the resulting residue was added AcOH (5 ml), water (0.5 ml) and 2,4-difluorophenylhydrazine hydrochloride (0.56 g; 3.1 mmol) and the resulting solution heated at 100° C. for 3 h. The reaction mixture was concentrated, the residue was dissolved in CH2Cl2 (50 ml) and washed with satd. NaHCO3 (50 ml). The organic layer was separated (hydrophobic frit), concentrated and purified by ISCO to give 399 as a cream-coloured solid (0.31 g; 31%). δH (400 MHz, CDCl3) 3.41 (t, J=5.2, 2H), 4.36 (t, J=5.2, 2H), 6.89 (d, J=8.8, 1H), 7.14-7.20 (m, 2H), 7.27-7.30 (m, 1H), 7.55-7.61 (m, 1H), 7.69 (d, J=2.8, 1H), 8.16 (s, 1H). [M+H]+: 462

후처리

  1. concentrationwas concentrated
  2. temperaturethe resulting solution heated at 100° C. for 3 h
  3. concentrationThe reaction mixture was concentrated
  4. dissolutionthe residue was dissolved in CH2Cl2 (50 ml)
  5. washwashed with satd
  6. customThe organic layer was separated (hydrophobic frit)
  7. concentrationconcentrated
  8. custompurified by ISCO

출처 및 근거

ORD 기록
ord-02886a89582048a08acd9ea42fc516da
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846762B2

연결된 노트

불러오는 중…