1,8-Diazabicyclo(5.4.0)undec-7-ene → tert-butyl 3-(cyanomethyl)-3-[4-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-1-yl]azetidine-1-carboxylate

HRID 571465Notes

Reaction equation

[NH:1]1[CH:5]=[C:4]([C:6]2[CH:11]=[CH:10][N:9]=[C:8]3[N:12]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])[CH:13]=[CH:14][C:7]=23)[CH:3]=[N:2]1.[C:23]([CH:25]=[C:26]1[CH2:29][N:28]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:27]1)#[N:24].N12CCCN=C1CCCCC2>C(#N)C>[C:23]([CH2:25][C:26]1([N:1]2[CH:5]=[C:4]([C:6]3[CH:11]=[CH:10][N:9]=[C:8]4[N:12]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])[CH:13]=[CH:14][C:7]=34)[CH:3]=[N:2]2)[CH2:29][N:28]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:27]1)#[N:24]

Participants

Conditions

Temperature: 50 °C

Procedure

A mixture of 4-(1H-pyrazol-4-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridine (0.527 g, 1.68 mmol), tert-butyl 3-(cyanomethylene)azetidine-1-carboxylate (0.358 g, 1.84 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (135 μL, 0.903 mmol) in acetonitrile (4.0 mL) was heated at 50° C. for 1 hour. After cooling, the solvent was removed under reduced pressure. The residue was diluted with ethyl acetate, neutralized with 0.5 N HCl aqueous solutions, washed brine, dried over Na2SO4, filtered and concentrated under reduced pressure to afford the desired product (0.85 g, quantitative) which was directly used in next step reaction without further purification. LCMS (M+H)+: m/z=509.3.

Workup

temperatureAfter cooling
customthe solvent was removed under reduced pressure
additionThe residue was diluted with ethyl acetate
washwashed brine
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-38b54d91afc548ff918a16d7c662d961
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09023840B2

Reaction notes

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