3-Methylbut-1-yne → HCID 178442170, compound

HRID 1875193Notes

Reaction equation

HRID 1875193 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.[CH3:29][CH:30]([CH3:33])[C:31]#[CH:32]>C1COCC1.[Pd].[Cu]I>[Cl:27][C:23]1[N:24]=[CH:25][NH:26][C:22]=1[C:20]([NH:19][CH2:18][C:13]1[CH:14]=[CH:15][C:16]([Cl:17])=[C:11]([O:10][C:4]2[CH:3]=[C:2]([C:32]#[C:31][CH:30]([CH3:33])[CH3:29])[CH:7]=[C:6]([C:8]#[N:9])[CH:5]=2)[C:12]=1[F:28])=[O:21]

Participants

6

Reactant 2

HCID 690193-Methylbut-1-yneHCID 178509438HCID 178509438, compound

Product 1

HCID 178442170HCID 178442170, compoundYield 53.1%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 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 (95 mg, 0.196 mmol), Palladium dichloropistriphenylphosphine (103 mg, 0.196 mmol), 3-methyl-1-butyne (26.7 mg, 0.392 mmol) and copper(I) iodide (1.869 mg, 9.81 μmol) in THF (4 ml) was added TEA (0.141 ml, 1.012 mmol) 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 4-chloro-N-[(4-chloro-3-{[3-cyano-5-(3-methyl-1-butyn-1-yl)phenyl]oxy}-2-fluorophenyl)methyl]-1H-imidazole-5-carboxamide (49 mg, 0.104 mmol, 53% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.25 (d, 1H), 7.73 (s, 1H), 7.57 (s, 1H), 7.41-7.50 (m, 2H), 7.32 (t, 1H), 7.11 (s, 1H), 4.49 (d, 2H), 2.76 (dt, 1H), 1.15 (d, 6H). LC-MS (ES+) m/z 471.13, [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-d3db00aa4211416b8af475a32d7c1bb7
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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