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 84651Notes

Reaction equation

HRID 84651 reaction equation
[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

Participants

7

Reactant 4

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

Product 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]azuleneYield 31%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

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

Workup

  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

Sources & evidence

ORD record
ord-02886a89582048a08acd9ea42fc516da
Source dataset
uspto-grants-2014_09
Patent number
US08846762B2

Reaction notes

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