Pyridine → ethyl 2-(7-(3-(hydroxymethyl)-1H-1,2,4-triazol-1-yl)-4-methoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-oxoacetate

HRID 885062Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:8]=[N:7][C:6]([N:9]2[CH:13]=[N:12][C:11]([CH2:14][OH:15])=[N:10]2)=[C:5]2[NH:16][CH:17]=[CH:18][C:4]=12.C([Mg]Br)C.N1C=CC=CC=1.Cl[C:30](=[O:36])[C:31]([O:33][CH2:34][CH3:35])=[O:32]>C1COCC1>[OH:15][CH2:14][C:11]1[N:12]=[CH:13][N:9]([C:6]2[N:7]=[CH:8][C:3]([O:2][CH3:1])=[C:4]3[C:18]([C:30](=[O:36])[C:31]([O:33][CH2:34][CH3:35])=[O:32])=[CH:17][NH:16][C:5]=23)[N:10]=1

Participants

Conditions

Temperature: -40 °C

Procedure

To a solution of (1-(4-methoxy-1H-pyrrolo[2,3-c]pyridin-7-yl)-1H-1,2,4-triazol-3-yl)methanol (70 mg, 0.285 mmol) in THF (5 mL) was added ethylmagnesium bromide (1.284 mL, 1.284 mmol) at −40° C. After stirring at −5° C. for 1H, pyridine (0.012 mL, 0.143 mmol) was added quickly. The mixture was cooled to −40° C. and ethyl 2-chloro-2-oxoacetate (0.130 mL, 1.142 mmol) was added. After stirring at −40° C. for 30 min, the reaction mixture was quenched by adding i-PrOH and water. The mixture was extracted with EtOAc (2×40 mL). The organic layers were combined, washed with brine (30 mL), dried over MgSO4 and concentrated under vacuum to give crude product ethyl 2-(7-(3-(hydroxymethyl)-1H-1,2,4-triazol-1-yl)-4-methoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-oxoacetate (70 mg, 0.203 mmol, 71.0% yield). LCMS: m/z 346.1 (M+H)+, 1.42 min (method 8).

Workup

additionwas added quickly
customthe reaction mixture was quenched
additionby adding i-PrOH and water
extractionThe mixture was extracted with EtOAc (2×40 mL)
washwashed with brine (30 mL)
dry with materialdried over MgSO4
concentrationconcentrated under vacuum

Sources & evidence

ORD record: ord-81a1e40feb1b4a38ac0b11c1e0a75f2a
Source dataset: uspto-grants-2012_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08242124B2

Reaction notes

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