Sodium hydride → 5-bromo-2-[(3,5-dibutyl-1H-1,2,4-triazol-1-yl)methyl]pyridine

HRID 864451Notes

Reaction equation

[CH2:1]([C:5]1[N:9]=[C:8]([CH2:10][CH2:11][CH2:12][CH3:13])[NH:7][N:6]=1)[CH2:2][CH2:3][CH3:4].[H-].[Na+].[H][H].[Br:18][C:19]1[CH:20]=[CH:21][C:22]([CH2:25]Br)=[N:23][CH:24]=1>CN(C)C=O.CO>[Br:18][C:19]1[CH:20]=[CH:21][C:22]([CH2:25][N:6]2[C:5]([CH2:1][CH2:2][CH2:3][CH3:4])=[N:9][C:8]([CH2:10][CH2:11][CH2:12][CH3:13])=[N:7]2)=[N:23][CH:24]=1

Participants

Conditions

Temperature: 3 °C

Procedure

Under nitrogen 3.19 g (18 mmol) of solid 3,5-dibutyl-1H-1,2,4-triazole from step 3 was added in small portions of 25 mmol of sodium hydride in 45 ml of dimethylformamide (DMF); stirring was continued until hydrogen evolution had ceased. The anion solution was cooled to 3° C. and treated with a solution of the crude 5-bromo-2-bromomethylpyridine from step 2 (17 mmol) in 20 ml of dry DMF. The reaction was allowed to warm to ambient temperature and stir overnight. Methanol (10 ml) was added to destroy any unreacted sodium hydride and the DMF was removed in vacuo. The residue was dissolved in ethyl acetate, washed with water, and dried (MgSO4). Silica gel chromatography (Waters Prep-500A) using ethyl acetate/hexane (40:60) gave 4.16 g (69% from triazole) of 5-bromo-2-[(3,5-dibutyl-1H-1,2,4-triazol-1-yl)methyl]pyridine as a brown oil: NMR (CDCl3) δ0.88 (t, J=7 Hz, 3H), 0.93 (t, J=7 Hz, 3H), 1.23-1.46 (m, 4H), 1.59-1.78 (m, 4H), 2.63-2.74 (m, 4H), 5.30 (s, 2H), 6.92 (d, J=8 Hz, 1H), 7.72 (dd, J=8 and 2 Hz, 1H), 8.61 (d, J=2 Hz, 1H).

Workup

temperatureto warm to ambient temperature
stirringstir overnight
customto destroy any unreacted sodium hydride
customthe DMF was removed in vacuo
dissolutionThe residue was dissolved in ethyl acetate
washwashed with water
dry with materialdried (MgSO4)

Sources & evidence

ORD record: ord-623b2a61355b4392a72de1c29657da66
Source dataset: uspto-grants-1996_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05563139

Reaction notes

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