Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → HCID 178464937, compound
Reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:9][CH:10]=[C:11]([C:13]([OH:15])=O)[N:12]=2)=[C:4]([F:16])[CH:3]=1.[CH:17]([NH:20][N:21]=[C:22]([NH2:24])[CH3:23])([CH3:19])[CH3:18].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:9][CH:10]=[C:11]([C:13]([N:24]=[C:22]([NH:21][NH:20][CH:17]([CH3:19])[CH3:18])[CH3:23])=[O:15])[N:12]=2)=[C:4]([F:16])[CH:3]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
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-528ed26273da4ce6823e51254b8e57a8
- Source dataset
- uspto-grants-2016_04
- Patent number
- US09303043B2
Reaction notes
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