Diethyl Ether → 4-[1-(4-Fluoro-phenyl)-2-methyl-1H-imidazol-4-ylethynyl]-2-methyl-pyridine

HRID 860150Notes

Reaction equation

HRID 860150 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([C:8]#[C:9][C:10]2[N:11]=[C:12]([CH3:15])[NH:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1.[F:16][C:17]1[CH:22]=[CH:21][C:20](B(O)O)=[CH:19][CH:18]=1.C(OCC)C>ClCCl>[F:16][C:17]1[CH:22]=[CH:21][C:20]([N:13]2[CH:14]=[C:10]([C:9]#[C:8][C:6]3[CH:5]=[CH:4][N:3]=[C:2]([CH3:1])[CH:7]=3)[N:11]=[C:12]2[CH3:15])=[CH:19][CH:18]=1

Participants

5

Reactant 3

HCID 3283Diethyl EtherHCID 2856454-Fluorophenylboronic acidHCID 178418884HCID 178418884, compound

Product 1

HCID 100856604-[1-(4-Fluoro-phenyl)-2-methyl-1H-imidazol-4-ylethynyl]-2-methyl-pyridine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-Methyl-4-(2-methyl-1H-imidazol-4-ylethynyl)-pyridine (II-1) (200 mg, 1.01 mmol) was dissolved in 10 mL dichloromethane. Powdered molecular sieves (3 Å, 200 mg), 4-fluorobenzene boronic acid (284 mg, 2.02 mmol) and [Cu(OH)TMEDA]2Cl2 (47 mg, 0.10 mmol) were added. Oxygen was bubbled through the reaction mixture for 5 min and stirring was continued at RT overnight. The reaction mixture was filtered through a dicalite speed plus pad and washed with 50 mL dichloromethane. The filtrate was washed with 50 ml water, dried with magnesium sulfate, filtered and evaporated. The crude product was purified by flash chromatography on silica gel (dichloromethane/methanol 100:0→85:15 gradient) and a mixture of 2 regioisomers was isolated. The desired compound was obtained by recrystallization from diethylether as a white solid (151 mg, 51%), mp=151° C., MS: m/e=292.1 (M+H+).

Workup

  1. customOxygen was bubbled through the reaction mixture for 5 min
  2. filtrationThe reaction mixture was filtered through a dicalite speed plus pad
  3. washwashed with 50 mL dichloromethane
  4. washThe filtrate was washed with 50 ml water
  5. dry with materialdried with magnesium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customThe crude product was purified by flash chromatography on silica gel (dichloromethane/methanol 100:0→85:15 gradient)
  9. additiona mixture of 2 regioisomers
  10. customwas isolated

Sources & evidence

ORD record
ord-169251d280694d4b94bb6544d0de740a
Source dataset
uspto-grants-2006_12
Patent number
US07153874B2

Reaction notes

Loading…