Diethyl Ether → 1-[3-(6-chloro-1-methyl-1H-benzoimidazol-2-yl)-pyridin-4-yl]-ethanol

HRID 1897618Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([C:10]3[CH:11]=[N:12][CH:13]=[CH:14][C:15]=3[CH:16]=[O:17])[N:7]([CH3:18])[C:6]=2[CH:19]=1.C[Mg+].[Br-].[CH2:23](OCC)C>C1COCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([C:10]3[CH:11]=[N:12][CH:13]=[CH:14][C:15]=3[CH:16]([OH:17])[CH3:23])[N:7]([CH3:18])[C:6]=2[CH:19]=1

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of 3-(6-chloro-1-methyl-1H-benzoimidazol-2-yl)-pyridine-4-carbaldehyde (75 mg, 0.276 mmol) in THF (4 mL) at −78° C. was added 3 M MeMgBr in diethyl ether (0.138 mL, 0.414 mmol) and the mixture was stirred at −78° C. for 0.5 hr. The reaction was quenched with water (0.5 mL) and the mixture was warmed to room temperature. It was concentrated in vacuo. The crude was taken up in MeOH (5 mL) and purified on RP-HPLC using RP18 column and gradient 0.1% aqueous NH4OH in acetonitrile, followed with a second purification by silica gel flash chromatography DCM-MeOH (9:1) to afford 1-[3-(6-chloro-1-methyl-1H-benzoimidazol-2-yl)-pyridin-4-yl]-ethanol. 1H NMR (400 MHz, MeOD) δ ppm 1.34 (d, J=6.6 Hz, 3H), 3.73 (s, 3H), 4.81-4.86 (m, 1H), 7.38 (dd, J=8.6, 2.0 Hz, 1H), 7.72 (d, J=9.1 Hz, 1H), 7.73 (d, J=2.0 Hz, 1H), 7.86 (d, J=5.3 Hz, 1H), 8.63 (s, 1H), 8.79 (d, J=5.3 Hz, 1H); HRMS: (ESI) ink 288.0894 [(M+H)+ Calcd for C15H14ClN3O 288.0904].

Workup

customThe reaction was quenched with water (0.5 mL)
temperaturethe mixture was warmed to room temperature
concentrationIt was concentrated in vacuo
custompurified on RP-HPLC
customfollowed with a second purification by silica gel flash chromatography DCM-MeOH (9:1)

Sources & evidence

ORD record: ord-f6b3e659313e4ae2b345630e92b2ae4f
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08519134B2

Reaction notes

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