Methanol → 8-bromo-2-[4-(2-chloro-phenyl)-4H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene
Reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9]([C:11]1[S:12][C:13]2[CH2:14][CH2:15][O:16][C:17]3[CH:24]=[C:23]([Br:25])[CH:22]=[CH:21][C:18]=3[C:19]=2[N:20]=1)=S.O.[NH2:27][NH2:28].[CH3:29]O>>[Br:25][C:23]1[CH:22]=[CH:21][C:18]2[C:19]3[N:20]=[C:11]([C:9]4[N:8]([C:3]5[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=5[Cl:1])[CH:29]=[N:28][N:27]=4)[S:12][C:13]=3[CH2:14][CH2:15][O:16][C:17]=2[CH:24]=1Participants
4
Conditions
- Temperature
- 90 °C
Procedure
A mixture of 8-bromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carbothioic acid (2-chloro-phenyl)-amide (160 mg), methanol (10 mL) and hydrazine hydrate (170 μL) was heated to reflux for 6 hours. The reaction mixture was then cooled and the solid collected by filtration. A mixture of this solid (144 mg) and triethyl orthoformate (5 mL) was heated to 90° C. for 2 hours and then to 130° C. for 2 hours. The reaction mixture was then cooled and the solvent removed in vacuo and the residue purified using flash chromatography to yield 314 (55 mg). NMR: (CDCl3): 3.32 (2H, t), 4.36 (2H, t), 6.96 (1H, dd), 7.11-7.16 (2H, m), 7.49-7.68 (4H, m), 8.30 (1H, s). MS: (ESI+) MH+ 461
Workup
- temperaturewas heated
- temperatureto reflux for 6 hours
- temperatureThe reaction mixture was then cooled
- filtrationthe solid collected by filtration
- additionA mixture of this solid (144 mg) and triethyl orthoformate (5 mL)
- temperatureThe reaction mixture was then cooled
- customthe solvent removed in vacuo
- customthe residue purified
Sources & evidence
- ORD record
- ord-1efbdd3a0a8e4f36b75910b8b05d552e
- Source dataset
- uspto-grants-2016_04
- Patent number
- US09309265B2
Reaction notes
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