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

HRID 885066Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:8]=[N:7][C:6]([N:9]2[CH:13]=[N:12][C:11]([CH:14]([OH:16])[CH3:15])=[N:10]2)=[C:5]2[NH:17][CH:18]=[CH:19][C:4]=12.C([Mg]Br)C.N1C=CC=CC=1.Cl[C:31](=[O:37])[C:32]([O:34][CH2:35][CH3:36])=[O:33]>C1COCC1>[OH:16][CH: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:19]([C:31](=[O:37])[C:32]([O:34][CH2:35][CH3:36])=[O:33])=[CH:18][NH:17][C:5]=23)[N:10]=1)[CH3:15]

Participants

Conditions

Temperature: -5 °C

Procedure

To a solution of 1-(1-(4-methoxy-1H-pyrrolo[2,3-c]pyridin-7-yl)-1H-1,2,4-triazol-3-yl)ethanol (100 mg, 0.386 mmol) in THF (8 mL) was added ethylmagnesium bromide (1.736 mL, 1.736 mmol) at −40° C. After stirring at −5° C. for 1 h, pyridine (0.016 mL, 0.193 mmol) was added quickly. The mixture was cooled to −40° C. and ethyl 2-chloro-2-oxoacetate (0.176 mL, 1.543 mmol) was added. After stirring at −40° C. for 30 min, the reaction was quenched by adding i-PrOH and water. The mixture was extracted with EtOAc (2×50 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-(1-hydroxyethyl)-1H-1,2,4-triazol-1-yl)-4-methoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-oxoacetate (100 mg, 0.278 mmol, 72.2% yield). LCMS: m/z 360.1 (M+H)+, 1.53 min (method 8).

Workup

temperatureThe mixture was cooled to −40° C.
stirringAfter stirring at −40° C. for 30 min
customthe reaction was quenched
additionby adding i-PrOH and water
extractionThe mixture was extracted with EtOAc (2×50 mL)
washwashed with brine (30 mL)
dry with materialdried over MgSO4
concentrationconcentrated under vacuum

Sources & evidence

ORD record: ord-2f6fa217da924480b88ce4170049618e
Source dataset: uspto-grants-2012_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08242124B2

Reaction notes

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