1-Butyne → HCID 178441013, compound

HRID 1875195Notes

Reaction equation

HRID 1875195 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:10][C:11]2[C:12]([F:28])=[C:13]([CH2:18][NH:19][C:20]([C:22]3[NH:26][CH:25]=[N:24][C:23]=3[Cl:27])=[O:21])[CH:14]=[CH:15][C:16]=2[Cl:17])[CH:5]=[C:6]([C:8]#[N:9])[CH:7]=1.[CH:29]#[C:30][CH2:31][CH3:32]>C1COCC1.[Cu]I>[C:29]([C:2]1[CH:3]=[C:4]([O:10][C:11]2[C:12]([F:28])=[C:13]([CH2:18][NH:19][C:20]([C:22]3[NH:26][CH:25]=[N:24][C:23]=3[Cl:27])=[O:21])[CH:14]=[CH:15][C:16]=2[Cl:17])[CH:5]=[C:6]([C:8]#[N:9])[CH:7]=1)#[C:30][CH2:31][CH3:32]

Participants

5

Reactant 2

HCID 78461-ButyneHCID 178509438HCID 178509438, compound

Product 1

HCID 178441013HCID 178441013, compoundYield 28%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of N-({3-[(3-bromo-5-cyanophenyl)oxy]-4-chloro-2-fluorophenyl}methyl)-4-chloro-1H-imidazole-5-carboxamide (65 mg, 0.134 mmol), Palladium dichlorobistriphenylphosphine(II) (7.01 mg, 0.013 mmol), copper(I)iodide (25.6 mg, 0.134 mmol) and TEA (0.019 ml, 0.134 mmol) in THF (5 ml) was bubbled 1-butyne (7.26 mg, 0.134 mmol) for 5 minutes and the reaction mixture was irradiated in a personal microwave reactor for 10 minutes at 120° C. The solvent was removed and the crude material was purified via reverse phase HPLC to give N-[(3-{[3-(1-butyn-1-yl)-5-cyanophenyl]oxy}-4-chloro-2-fluorophenyl)methyl]-4-chloro-1H-imidazole-5-carboxamide (17 mg, 0.037 mmol, 28% yield). 1H NMR (400 MHz, METHANOL-d4) δ ppm 7.71 (br. s., 1H), 7.40 (s, 1H), 7.28-7.39 (m, 3H), 7.17 (s, 1H), 7.05 (s, 1H), 4.62 (s, 2H), 2.38 (q, 2H), 1.17 (t, 3H). LC-MS (ES+) m/z 457.14, [M+H].

Workup

  1. customthe reaction mixture was irradiated in a personal microwave reactor for 10 minutes at 120° C
  2. customThe solvent was removed
  3. customthe crude material was purified via reverse phase HPLC

Sources & evidence

ORD record
ord-17a40161273c4b7dbfac13b6ab6afbbb
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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