Chloropyruvic acid → HCID 178524791, compound
Reaction equation
BrC1C=CC(C2NC=C(C3N(C(C)C)N=C(C)N=3)N=2)=C(F)C=1.Cl.[Br:24][C:25]1[CH:33]=[CH:32][C:28]([C:29](=[NH:31])[NH2:30])=[C:27]([F:34])[CH:26]=1.Cl[CH2:36][C:37](=O)[C:38]([OH:40])=[O:39]>>[Br:24][C:25]1[CH:33]=[CH:32][C:28]([C:29]2[NH:30][CH:36]=[C:37]([C:38]([OH:40])=[O:39])[N:31]=2)=[C:27]([F:34])[CH:26]=1Participants
Procedure
Scheme 11 shows the synthesis of 5-(2-(4-bromo-2-fluorophenyl)-1H-imidazol-4-yl)-1-isopropyl-3-methyl-1H-1,2,4-triazole V from 4-bromo-2-fluorobenzimidamide hydrochloride 12. 3-Chloro-2-oxopropanoic acid and 12 are reacted with base to give 2-(4-bromo-2-fluorophenyl)-1H-imidazole-4-carboxylic acid 30. Alternatively, 3-bromo-2-oxopropanoic acid can be reacted with 12 to give 30. Reaction of 30 with N′-isopropylacetohydrazonamide 6 and coupling reagent HBTU (N,N,N′,N′-tetramethyl-O-(1H-benzotriazol-1-yl)uronium hexafluorophosphate, 0-(Benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate, CAS Ref No. 94790-37-1) in DMF gives intermediate, 2-(4-bromo-2-fluorophenyl)-N-(1-(2-isopropylhydrazinyl)ethylidene)-1H-imidazole-4-carboxamide 31 which need not be isolated and cyclizes upon heating to give V. Alternatively, 5-(2-(4-chloro-2-fluorophenyl)-1H-imidazol-4-yl)-1-isopropyl-3-methyl-1H-1,2,4-triazole 44, the chloro version of V, can be prepared from 4-chloro-2-fluorobenzonitrile 38 (Scheme 15)
Sources & evidence
- ORD record
- ord-24bbcead7c58444e96b3801769d12222
- Source dataset
- uspto-grants-2016_04
- Patent number
- US09303043B2
Reaction notes
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