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

反応式

HRID 84651 の反応式
[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

参加物

7

反応物 4

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

生成物 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]azulene収率 31%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 1140Toluene溶媒

反応条件

温度
100 °C

実験手順

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

後処理

  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

出典と根拠

ORDレコード
ord-02886a89582048a08acd9ea42fc516da
出典データセット
uspto-grants-2014_09
特許番号
US08846762B2

関連ノート

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