Cyclopropylacetylene → HCID 178509680, compound

HRID 1875192Notes

Reaction equation

HRID 1875192 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]1([C:32]#[CH:33])[CH2:31][CH2:30]1>C1COCC1.[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:33]#[C:32][CH:29]3[CH2:31][CH2:30]3)[CH:7]=[C:6]([C:8]#[N:9])[CH:5]=2)[C:12]=1[F:28])=[O:21]

Participants

5

Reactant 2

HCID 138823CyclopropylacetyleneHCID 178509438HCID 178509438, compound

Product 1

HCID 178509680HCID 178509680, compoundYield 52%

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 (95.0 mg, 0.196 mmol), cyclopropylacetylene (25.9 mg, 0.392 mmol), copper(I) iodide (1.869 mg, 9.81 μmol) and Palladiumbischlorobistriphenylphosphine(II) (10.25 mg, 0.020 mmol) in THF (6 ml) was added TEA (0.137 ml, 0.981 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-(cyclopropylethynyl)phenyl]oxy}-2-fluorophenyl)methyl]-1H-imidazole-5-carboxamide (48 mg, 0.102 mmol, 52% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.28 (br. s., 1H), 7.76 (s, 1H), 7.59 (s, 1H), 7.39-7.53 (m, 2H), 7.34 (t, 1H), 7.14 (s, 1H), 4.51 (d, 2H), 1.47-1.64 (m, 1H), 0.83-1.01 (m, 2H), 0.71-0.81 (m, 2H). LC-MS (ES+) m/z 469.09, [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-27234a4d7e1049f2889a1c7e6f4b2971
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

Loading…