(2R)-but-3-yn-2-ol → HCID 178462269, compound

HRID 1875196Notes

Reaction equation

HRID 1875196 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.[CH3:28][C@@H:29]([OH:32])[C:30]#[CH:31]>C1COCC1.CCOC(C)=O.[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:31]#[C:30][C@H:29]([OH:32])[CH3:28])[CH:7]=[C:6]([Cl:8])[CH:5]=2)[C:11]=1[F:27])=[O:20]

Participants

6

Reactant 2

HCID 638102(2R)-but-3-yn-2-olHCID 178522959HCID 178522959, compound

Product 1

HCID 178462269HCID 178462269, compoundYield 23.2%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-({3-[(3-bromo-5-chlorophenyl)oxy]-4-chloro-2-fluorophenyl}methyl)-4-chloro-1H-imidazole-5-carboxamide (70 mg, 0.142 mmol), palladiumbisdichlorobistriphenylphosphine (9.96 mg, 0.014 mmol), copper(I) iodide (1.351 mg, 7.09 μmol) and TEA (0.099 ml, 0.710 mmol) in THF (6 ml) was added (2R)-3-butyn-2-ol (24.85 mg, 0.355 mmol) and the reaction mixture was irradiated in a personal microwave reaction for 10 minutes at 120° C. The reaction mixture was diluted with EtOAc and washed with water. The solvent was removed and the crude material was purified via reverse phase HPLC to give 4-chloro-N-{[4-chloro-3-({3-chloro-5-[(3R)-3-hydroxy-1-butyn-1-yl]phenyl}oxy)-2-fluorophenyl]methyl}-1H-imidazole-5-carboxamide (16 mg, 0.033 mmol, 23% yield). 1H NMR (400 MHz, METHANOL-d4) δ ppm 7.24-7.45 (m, 3H), 7.11 (s, 1H), 6.89 (s, 1H), 6.74 (s, 1H), 4.47-4.70 (m, 3H), 1.41 (d, 3H). LC-MS (ES+) m/z 482.03, [M+H].

Workup

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

Sources & evidence

ORD record
ord-ba6c4b2eea554c68ba4bebfacde85dc9
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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