Hydroxylamine → HCID 178513303, compound

HRID 624622Notes

Reaction equation

HRID 624622 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:9]C=C(C3N(C(C)C)N=C(C)N=3)[N:12]=2)=[C:4]([F:22])[CH:3]=1.ClC1C=CC(C#N)=C(F)C=1.N[OH:34]>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[NH:9])[NH:12][OH:34])=[C:4]([F:22])[CH:3]=1

Participants

4

Reactant 3

HCID 787HydroxylamineHCID 936554-Chloro-2-fluorobenzonitrile2×HCID 178432630HCID 178432630, compound

Product 1

HCID 178513303HCID 178513303, compound

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-dba2729adc3843bc8ed24ea3199b4111
Source dataset
uspto-grants-2016_04
Patent number
US09303043B2

Reaction notes

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