4-{3-[7-(2-Cyano-2,2-dimethyl-acetyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-phenyl}-piperazine-1-carboxylic acid tert-butyl ester → 2,2-Dimethyl-3-oxo-3-[2-(3-piperazin-1-yl-phenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-propionitrile

HRID 1677431Notes

Reaction equation

HRID 1677431 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([C:20]3[N:21]=[C:22]4[C:28]([C:29](=[O:35])[C:30]([C:33]#[N:34])([CH3:32])[CH3:31])=[CH:27][NH:26][C:23]4=[N:24][CH:25]=3)[CH:15]=2)[CH2:10][CH2:9]1)=O)(C)(C)C>FC(F)(F)C(O)C(F)(F)F>[CH3:31][C:30]([CH3:32])([C:29](=[O:35])[C:28]1[C:22]2[C:23](=[N:24][CH:25]=[C:20]([C:16]3[CH:17]=[CH:18][CH:19]=[C:14]([N:11]4[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]4)[CH:15]=3)[N:21]=2)[NH:26][CH:27]=1)[C:33]#[N:34]

Participants

3

Reactant 1

HCID 595410684-{3-[7-(2-Cyano-2,2-dimethyl-acetyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-phenyl}-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 595409962,2-Dimethyl-3-oxo-3-[2-(3-piperazin-1-yl-phenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-propionitrile

Reagents, catalysts & solvents 1

HCID 135291,1,1,3,3,3-Hexafluoro-2-propanolSolvent

Procedure

A solution of 4-{3-[7-(2-Cyano-2,2-dimethyl-acetyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-phenyl}-piperazine-1-carboxylic acid tert-butyl ester from step 1 in hexafluoroisopropanol was heated at 150° C. in a microwave oven for 45 min. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel with a mixture of 28% aqueous ammonium hydroxide:methanol:DCM (1:10:60) in DCM (20% to 80% gradient over 30 min) to give 39 mg of the desired product as a yellow powder. 1H NMR (CDCl3, 400 MHz): δ 8.81 (s, 1H), 8.50 (s, 1H), 7.91 (s, 1H), 7.60-7.54 (m, 1H), 7.42 (t, J=7.9 Hz, 1H), 7.08-7.04 (m, 1H), 3.35 (t, J=4 Hz, 2H), 3.14 (t, J=4 Hz, 2H), 1.92 (s, 6H); MS [M+H]+: 375.

Workup

  1. concentrationconcentrated under reduced pressure
  2. customThe residue was purified by flash column chromatography on silica gel with a mixture of 28% aqueous ammonium hydroxide:methanol:DCM (1:10:60) in DCM (20% to 80% gradient over 30 min)

Sources & evidence

ORD record
ord-4b448108dfb2458292c36f13d4c68354
Source dataset
uspto-grants-2011_08
Patent number
US08008298B2

Reaction notes

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