Ethyl propiolate → HCID 178472243, compound

HRID 624623Notes

Reaction equation

[Cl:1][C:2]1[CH:11]=[CH:10][C:5]([C:6](=[NH:9])[NH:7][OH:8])=[C:4]([F:12])[CH:3]=1.[C:13]([O:17][CH2:18][CH3:19])(=[O:16])[C:14]#[CH:15]>>[Cl:1][C:2]1[CH:11]=[CH:10][C:5]([C:6](=[NH:9])[NH:7][O:8][CH:15]=[CH:14][C:13]([O:17][CH2:18][CH3:19])=[O:16])=[C:4]([F:12])[CH:3]=1

Participants

Reactant 2

HCID 12182Ethyl propiolate

HCID 178513303HCID 178513303, compound

Product 1

HCID 178472243HCID 178472243, 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-0603541e54334ee8830ba2c775ff90fc
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09303043B2

Reaction notes

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