Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → HCID 178464938, compound

HRID 624624Notes

Reaction equation

HRID 624624 reaction equation
[Cl: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>[Cl: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]=1

Participants

5

Reactant 3

HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 74037752N'-isopropylacetohydrazonamideHCID 178524794HCID 178524794, compound

Product 1

HCID 178464938HCID 178464938, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Scheme 15 shows the synthesis of 5-(2-(4-chloro-2-fluorophenyl)-1H-imidazol-4-yl)-1-isopropyl-3-methyl-1H-1,2,4-triazole 44 from 4-chloro-2-fluorobenzonitrile 38. Addition of hydroxylamine to the nitrile of 38 gave 4-chloro-2-fluoro-N-hydroxybenzimidamide 39. Michael addition of 39 to ethyl propiolate gave ethyl 3-(4-chloro-2-fluorobenzimidamidooxy)acrylate 40. Heating 40 in diphenyl oxide gave cyclized imidazole, ethyl 2-(4-chloro-2-fluorophenyl)-1H-imidazole-4-carboxylate 41. Saponification of the ester of 41 with aqueous sodium hydroxide in tetrahydrofuran gave 2-(4-chloro-2-fluorophenyl)-1H-imidazole-4-carboxylic acid 42. Reaction of 42 with N′-isopropylacetohydrazonamide 6 and coupling reagent HBTU in DMF gives intermediate, 2-(4-chloro-2-fluorophenyl)-N-(1-(2-isopropylhydrazinyl)ethylidene)-1H-imidazole-4-carboxamide 43 which cyclizes upon heating to give 44.

Sources & evidence

ORD record
ord-649c0ae849e04ee6978e7013ef1a290f
Source dataset
uspto-grants-2016_04
Patent number
US09303043B2

Reaction notes

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