tert-butyl (2S)-2-[(E)-3-[[4-[[3-chloro-4-(2-pyridylmethoxy)phenyl]amino]-3-cyano-7-ethoxy-6-quinolyl]amino]-3-oxo-prop-1-enyl]pyrrolidine-1-carboxylate → (E)-N-[4-[[3-chloro-4-(2-pyridylmethoxy)phenyl]amino]-3-cyano-7-ethoxy-6-quinolyl]-3-[(2S)-pyrrolidin-2-yl]prop-2-enamide

HRID 2199335Notes

Reaction equation

HRID 2199335 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:44][CH2:45][CH3:46])=[C:24]([NH:27][C:28](=[O:43])/[CH:29]=[CH:30]/[C@@H:31]4[CH2:35][CH2:34][CH2:33][N:32]4C(OC(C)(C)C)=O)[CH:25]=3)[N:20]=[CH:19][C:18]=2[C:47]#[N:48])[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1>Cl.O1CCOCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:44][CH2:45][CH3:46])=[C:24]([NH:27][C:28](=[O:43])/[CH:29]=[CH:30]/[C@@H:31]4[CH2:35][CH2:34][CH2:33][NH:32]4)[CH:25]=3)[N:20]=[CH:19][C:18]=2[C:47]#[N:48])[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1

Participants

4

Reactant 1

HCID 68029382tert-butyl (2S)-2-[(E)-3-[[4-[[3-chloro-4-(2-pyridylmethoxy)phenyl]amino]-3-cyano-7-ethoxy-6-quinolyl]amino]-3-oxo-prop-1-enyl]pyrrolidine-1-carboxylate

Product 1

HCID 51039032(E)-N-[4-[[3-chloro-4-(2-pyridylmethoxy)phenyl]amino]-3-cyano-7-ethoxy-6-quinolyl]-3-[(2S)-pyrrolidin-2-yl]prop-2-enamideYield 14.6%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 312751,4-DioxaneSolvent

Procedure

tert-Butyl (2S)-2-[(E)-3-[[4-[[3-chloro-4-(2-pyridylmethoxy)phenyl]amino]-3-cyano-7-ethoxy-6-quinolyl]amino]-3-oxo-prop-1-enyl]pyrrolidine-1-carboxylate 2d (161 mg, 0.24 mmol) was dissolved in a solution of hydrogen chloride (2M) in 25 mL of 1,4-dioxane. After stirring for 12 hours, the reaction mixture was concentrated under reduced pressure and extracted with dichloromethane (50 mL×3). The combined organic extracts were washed with saturated brine (30 mL×2), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure and the resulting residue was purified by silica gel column chromatography with elution system A to obtain the title compound (E)-N-[4-[[3-chloro-4-(2-pyridylmethoxy)phenyl]amino]-3-cyano-7-ethoxy-6-quinolyl]-3-[(2S)-pyrrolidin-2-yl]prop-2-enamide 2 (20 mg, yield 14.6%) as a yellow solid.

Workup

  1. concentrationthe reaction mixture was concentrated under reduced pressure
  2. extractionextracted with dichloromethane (50 mL×3)
  3. washThe combined organic extracts were washed with saturated brine (30 mL×2)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customthe resulting residue was purified by silica gel column chromatography with elution system

Sources & evidence

ORD record
ord-07e6560c61d24a20ac0153f8c3df0ae2
Source dataset
uspto-grants-2016_06
Patent number
US09358227B2

Reaction notes

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