1,8-Diazabicyclo(5.4.0)undec-7-ene → 3-cyclopentyl-3-(4-{2-[2-(3,5-dimethoxyphenyl)ethyl]-5H-pyrrolo[2,3-b]pyrazin-6-yl}-1H-pyrazol-1-yl)propanenitrile

HRID 1052258Notes

Reaction equation

HRID 1052258 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:11][CH2:12][C:13]2[N:14]=[C:15]3[CH:21]=[C:20]([C:22]4[CH:23]=[N:24][NH:25][CH:26]=4)[N:19](S(C4C=CC=CC=4)(=O)=O)[C:16]3=[N:17][CH:18]=2)[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1.N12CCCN=C1CCCCC2.[CH:47]1(/[CH:52]=[CH:53]/[C:54]#[N:55])[CH2:51][CH2:50][CH2:49][CH2:48]1>C(#N)C>[CH:47]1([CH:52]([N:25]2[CH:26]=[C:22]([C:20]3[NH:19][C:16]4=[N:17][CH:18]=[C:13]([CH2:12][CH2:11][C:5]5[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=[C:3]([O:2][CH3:1])[CH:4]=5)[N:14]=[C:15]4[CH:21]=3)[CH:23]=[N:24]2)[CH2:53][C:54]#[N:55])[CH2:51][CH2:50][CH2:49][CH2:48]1

Participants

5

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 21427952(2E)-3-Cyclopentylprop-2-enenitrileHCID 89963624HCID 89963624, compound

Product 1

HCID 730565313-cyclopentyl-3-(4-{2-[2-(3,5-dimethoxyphenyl)ethyl]-5H-pyrrolo[2,3-b]pyrazin-6-yl}-1H-pyrazol-1-yl)propanenitrileYield 17.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirred solution of 2-[2-(3,5-dimethoxyphenyl)ethyl]-5-(phenylsulfonyl)-6-(1H-pyrazol-4-yl)-5H-pyrrolo[2,3-b]pyrazine (25.0 mg, 51.1 μmol) in acetonitrile (1.0 mL), 1,8-diazabicyclo[5.4.0]undec-7-ene (9.2 μL, 61.5 μmol) and (2E)-3-cyclopentylacrylonitrile (from Adesis, cat#9-245, 6.8 μL, 61.7 μmol) were added sequentially at room temperature. After 16 hours, the volatiles were removed and the crude mixture was purified on RP-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.05% TFA, at flow rate of 30 mL/min) to give the desired product (4.2 mg) as its TFA salt. LCMS calculated for C27H31N6O2 (M+H)+: m/z=471.2. Found: 471.2.

Workup

  1. customthe volatiles were removed
  2. customthe crude mixture was purified on RP-HPLC (XBridge C18 column
  3. washeluting with a gradient of acetonitrile/water containing 0.05% TFA, at flow rate of 30 mL/min)

Sources & evidence

ORD record
ord-599ce9382c4144f591b82f4463071b8b
Source dataset
uspto-grants-2016_07
Patent number
US09388185B2

Reaction notes

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