3-Butyn-1-OL → 4-(1-(1-(3-methoxy-4-((6-(trifluoromethyl)pyridin-3-yl)methoxy)phenyl)ethyl)-1H-benzo[d]imidazol-5-yl)but-3-yn-1-ol

HRID 706515Notes

Reaction equation

HRID 706515 reaction equation
I[C:2]1[CH:32]=[CH:31][C:5]2[N:6]([CH:9]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH2:18][C:19]4[CH:20]=[N:21][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:23][CH:24]=4)=[C:13]([O:29][CH3:30])[CH:12]=3)[CH3:10])[CH:7]=[N:8][C:4]=2[CH:3]=1.[CH2:33]([OH:37])[CH2:34][C:35]#[CH:36]>N1CCCCC1.[OH-].[NH4+].[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:30][O:29][C:13]1[CH:12]=[C:11]([CH:9]([N:6]2[C:5]3[CH:31]=[CH:32][C:2]([C:36]#[C:35][CH2:34][CH2:33][OH:37])=[CH:3][C:4]=3[N:8]=[CH:7]2)[CH3:10])[CH:16]=[CH:15][C:14]=1[O:17][CH2:18][C:19]1[CH:20]=[N:21][C:22]([C:25]([F:27])([F:26])[F:28])=[CH:23][CH:24]=1

Participants

7

Reactant 2

HCID 135663-Butyn-1-OLHCID 1181140745-iodo-1-(1-(3-methoxy-4-((6-(trifluoromethyl)pyridin-3-yl)methoxy)phenyl)ethyl)-1H-benzo[d]imidazole

Product 1

HCID 1180098394-(1-(1-(3-methoxy-4-((6-(trifluoromethyl)pyridin-3-yl)methoxy)phenyl)ethyl)-1H-benzo[d]imidazol-5-yl)but-3-yn-1-olYield 205%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8082PiperidineSolventHCID 14923Ammonium HydroxideSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred mixture of 5-iodo-1-(1-(3-methoxy-4-((6-(trifluoromethyl)pyridin-3-yl)methoxy)phenyl)ethyl)-1H-benzo[d]imidazole (0.210 g, 0.38 mmol), 3-butyn-1-ol (0.041 g, 0.57 mmol), copper(I) iodide (0.019 g, 0.10 mmol) in piperidine (4 mL) was added bis(triphenylphosphine)palladium(II) chloride (0.037 g, 0.053 mmol). The mixture heated to 100° C. in a microwave reactor. After 30 min, the reaction mixture was allowed to cool to room temperature and was diluted with 5N ammonium hydroxide solution (30 mL). The mixture was extracted with dichloromethane (3×25 mL). The combined organic phases were dried over magnesium sulfate, filtered, and concentrated to provide 0.386 g of a brown solid. Chromatographic purification (CombiFlash, 12 g SiO2 gold column, 1-5% methanol/dichloromethane elute) afforded 0.157 g (84%) of the product as a light yellow solid: 1H NMR (400 MHz, CDCl3) δ 8.78 (d, J=2.1 Hz, 1H), 8.04 (s, 1H), 8.00-7.93 (m, 1H), 7.90-7.84 (m, 1H), 7.72-7.68 (m, 1H), 7.28-7.23 (m, 1H), 7.13-7.08 (m, 1H), 6.87-6.82 (m, 1H), 6.76-6.64 (m, 2H), 5.55 (q, J=7.0 Hz, 1H), 5.19 (s, 2H), 3.83 (t, J=6.2 Hz, 2H), 3.77 (s, 3H), 2.71 (t, J=6.2 Hz, 2H), 2.00-1.92 (m, 4H) ppm; (M+1)=496.

Workup

  1. temperatureto cool to room temperature
  2. extractionThe mixture was extracted with dichloromethane (3×25 mL)
  3. dry with materialThe combined organic phases were dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-74005466884a4d708d330b509a2bbaee
Source dataset
uspto-grants-2015_11
Patent number
US09174986B2

Reaction notes

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