Cyclopropylacetylene → HCID 178522961, compound

HRID 1875167Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([O:9][C:10]2[C:11]([F:27])=[C:12]([CH2:17][NH:18][C:19]([C:21]3[NH:25][CH:24]=[N:23][C:22]=3[Cl:26])=[O:20])[CH:13]=[CH:14][C:15]=2[Cl:16])[CH:5]=[C:6]([Cl:8])[CH:7]=1.[CH:28]1([C:31]#[CH:32])[CH2:30][CH2:29]1>C1COCC1.[Cu]I>[Cl:26][C:22]1[N:23]=[CH:24][NH:25][C:21]=1[C:19]([NH:18][CH2:17][C:12]1[CH:13]=[CH:14][C:15]([Cl:16])=[C:10]([O:9][C:4]2[CH:3]=[C:2]([C:32]#[C:31][CH:28]3[CH2:30][CH2:29]3)[CH:7]=[C:6]([Cl:8])[CH:5]=2)[C:11]=1[F:27])=[O:20]

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of N-({3-[(3-bromo-5-chlorophenyl)oxy]-4-chloro-2-fluorophenyl}methyl)-4-chloro-1H-imidazole-5-carboxamide (125 mg, 0.253 mmol), tetrakistriphenylphosphine palladium(0) (35.6 mg, 0.051 mmol), copper(I) iodide (4.82 mg, 0.025 mmol) and TEA (0.177 ml, 1.266 mmol) in THF (5 ml) was added cyclopropylacetylene (0.043 ml, 0.507 mmol) and the reaction mixture was stirred for 5 hours at 60° C. The reaction mixture was adsorbed onto silica gel and the crude material was purified via silica gel chromatography to give 4-chloro-N-[(4-chloro-3-{[3-chloro-5-(cyclopropylethynyl)phenyl]oxy}-2-fluorophenyl)methyl]-1H-imidazole-5-carboxamide (95 mg, 0.198 mmol, 78% yield). 1H NMR (400 MHz, METHANOL-d4) δ ppm 7.70 (s, 1H), 7.21-7.39 (m, 2H), 7.02 (s, 1H), 6.81 (s, 1H), 6.64 (s, 1H), 4.62 (br. s., 2H), 1.35-1.50 (m, 1H), 0.78-0.90 (m, 2H), 0.57-0.77 (m, 2H). LC-MS (ES+) m/z 477.87, [M+H].

Workup

customthe crude material was purified via silica gel chromatography

Sources & evidence

ORD record: ord-e3e81a4055314f778f6ef5a713349021
Source dataset: uspto-grants-2012_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08304419B2

Reaction notes

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