Water → (E)-N-[4-[[3-chloro-4-(2-pyridylmethoxy)phenyl]amino]-3-cyano-7-ethoxy-6-quinolyl]-3-[(2S,4R)-4-hydroxy-1-methyl-pyrrolidin-2-yl]prop-2-enamide

HRID 2199341Notes

Reaction equation

HRID 2199341 reaction equation
[Si]([O:8][C@H:9]1[CH2:13][N:12]([CH3:14])[C@H:11](/[CH:15]=[CH:16]/[C:17]([NH:19][C:20]2[CH:21]=[C:22]3[C:27](=[CH:28][C:29]=2[O:30][CH2:31][CH3:32])[N:26]=[CH:25][C:24]([C:33]#[N:34])=[C:23]3[NH:35][C:36]2[CH:41]=[CH:40][C:39]([O:42][CH2:43][C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][N:45]=3)=[C:38]([Cl:50])[CH:37]=2)=[O:18])[CH2:10]1)(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.O>O1CCCC1>[Cl:50][C:38]1[CH:37]=[C:36]([NH:35][C:23]2[C:22]3[C:27](=[CH:28][C:29]([O:30][CH2:31][CH3:32])=[C:20]([NH:19][C:17](=[O:18])/[CH:16]=[CH:15]/[C@@H:11]4[CH2:10][C@@H:9]([OH:8])[CH2:13][N:12]4[CH3:14])[CH:21]=3)[N:26]=[CH:25][C:24]=2[C:33]#[N:34])[CH:41]=[CH:40][C:39]=1[O:42][CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][N:45]=1

Participants

5

Reactant 3

HCID 962WaterHCID 2724141Tetrabutylammonium FluorideHCID 67979671(E)-3-[(2S,4R)-4-(tert-butyl(dimethyl)silyl)oxy-1-methyl-pyrrolidin-2-yl]-N-[4-[[3-chloro-4-(2-pyridylmethoxy)phenyl]amino]-3-cyano-7-ethoxy-6-quinolyl]prop-2-enamide

Product 1

HCID 51038275(E)-N-[4-[[3-chloro-4-(2-pyridylmethoxy)phenyl]amino]-3-cyano-7-ethoxy-6-quinolyl]-3-[(2S,4R)-4-hydroxy-1-methyl-pyrrolidin-2-yl]prop-2-enamideYield 40.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(E)-3-[(2S,4R)-4-(tert-Butyl(dimethyl)silyl)oxy-1-methyl-pyrrolidin-2-yl]-N-[4-[[3-chloro-4-(2-pyridylmethoxy)phenyl]amino]-3-cyano-7-ethoxy-6-quinolyl]prop-2-enamide 3f (50 mg, 0.07 mmol) and tetrabutyl ammonium fluoride (51 mg, 0.21 mmol) were dissolved in 5 mL of tetrahydrofuran, and the mixture was stirred for 12 hours. The reaction mixture was added with 1 mL of water, 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,4R)-4-hydroxy-1-methyl-pyrrolidin-2-yl]prop-2-enamide 3 (17 mg, yield 40.4%) as a yellow solid.

Workup

  1. concentrationconcentrated 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-9df5b9ee820a4fe5ab302ad00f69996a
Source dataset
uspto-grants-2016_06
Patent number
US09358227B2

Reaction notes

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