Acetic Acid → 2-[5-Methyl-2-(2,2,2-trifluoro-ethyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1,3a,9-triaza-benzo[e]azulen-8-ol
Reaction equation
Cl[C:2]1[N:26]=[CH:25][C:5]2[C:6]3[N:10]([CH2:11][CH2:12][O:13][C:4]=2[CH:3]=1)[CH:9]=[C:8]([C:14]1[N:15]([CH2:20][C:21]([F:24])([F:23])[F:22])[N:16]=[C:17]([CH3:19])[N:18]=1)[N:7]=3.C(O)(=[O:29])C>>[CH3:19][C:17]1[N:18]=[C:14]([C:8]2[N:7]=[C:6]3[N:10]([CH2:11][CH2:12][O:13][C:4]4[CH:3]=[C:2]([OH:29])[N:26]=[CH:25][C:5]=43)[CH:9]=2)[N:15]([CH2:20][C:21]([F:22])([F:23])[F:24])[N:16]=1Participants
Procedure
A solution of 8-chloro-2-[5-methyl-2-(2,2,2-trifluoro-ethyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1,3a,9-triaza-benzo[e]azulene (4 g, 10.4 mmol) in acetic acid (100 mL) was heated to 150° C. for 65 hours. The reaction was cooled, concentrated in vacuo and loaded onto an Isolute SCX-2 cartridge, washing with methanol and eluting with 2M ammonia in methanol. Basic fractions were combined and concentrated in vacuo, the resultant residue was subjected to flash chromatography (SiO2, gradient 0 to 10% methanol in DCM) to give 2-[5-Methyl-2-(2,2,2-trifluoro-ethyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1,3a,9-triaza-benzo[e]azulen-8-ol. LCMS: RT=2.25 min, [M+H]+=367.33. 1H NMR 300 MHz (DMSO-d): δ 8.40 (1H, br, s), 7.94 (1H, s), 5.85 (1H, s), 5.77 (1H, s), 5.73 (2H, m), 4.56 (2H, m), 4.49 (2H, m), 2.29 (3H, s)
Workup
- temperatureThe reaction was cooled
- concentrationconcentrated in vacuo
- washwashing with methanol
- washeluting with 2M ammonia in methanol
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-fadf4f4a22444695bf74943749e27838
- Source dataset
- uspto-grants-2012_08
- Patent number
- US08242104B2
Reaction notes
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