1-{2-(Hex-5-enylmethylcarbamoyl)-4-[2-(6-methyl-2-pyridyl)-7-methoxy-8-methylquinolin-4-yloxy]cyclopentanecarbonyl}amino-2-vinylcyclopropanecarboxylic acid ethyl ester → 17-[2-(6-Methylpyridin-2-yl)-7-methoxy-8-methyl-quinolin-4-yloxy]-13-methyl-2,14-dioxo-3,13-diaza-tricyclo-[13.3.0.04,6]octadec-7-ene-4-carboxylic acid ethyl ester

HRID 407566Notes

Reaction equation

HRID 407566 reaction equation
[CH2:1]([O:3][C:4]([C:6]1([NH:11][C:12]([CH:14]2[CH2:18][CH:17]([O:19][C:20]3[C:29]4[C:24](=[C:25]([CH3:32])[C:26]([O:30][CH3:31])=[CH:27][CH:28]=4)[N:23]=[C:22]([C:33]4[CH:38]=[CH:37][CH:36]=[C:35]([CH3:39])[N:34]=4)[CH:21]=3)[CH2:16][CH:15]2[C:40](=[O:49])[N:41]([CH2:43][CH2:44][CH2:45][CH2:46]C=C)[CH3:42])=[O:13])[CH2:8][CH:7]1[CH:9]=[CH2:10])=[O:5])[CH3:2]>ClCCCl>[CH2:1]([O:3][C:4]([C:6]12[CH2:8][CH:7]1[CH:9]=[CH:10][CH2:46][CH2:45][CH2:44][CH2:43][N:41]([CH3:42])[C:40](=[O:49])[CH:15]1[CH:14]([CH2:18][CH:17]([O:19][C:20]3[C:29]4[C:24](=[C:25]([CH3:32])[C:26]([O:30][CH3:31])=[CH:27][CH:28]=4)[N:23]=[C:22]([C:33]4[CH:38]=[CH:37][CH:36]=[C:35]([CH3:39])[N:34]=4)[CH:21]=3)[CH2:16]1)[C:12](=[O:13])[NH:11]2)=[O:5])[CH3:2]

Participants

3

Reactant 1

HCID 668720481-{2-(Hex-5-enylmethylcarbamoyl)-4-[2-(6-methyl-2-pyridyl)-7-methoxy-8-methylquinolin-4-yloxy]cyclopentanecarbonyl}amino-2-vinylcyclopropanecarboxylic acid ethyl ester

Product 1

HCID 6687158517-[2-(6-Methylpyridin-2-yl)-7-methoxy-8-methyl-quinolin-4-yloxy]-13-methyl-2,14-dioxo-3,13-diaza-tricyclo-[13.3.0.04,6]octadec-7-ene-4-carboxylic acid ethyl esterYield 58.6%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

1-{2-(Hex-5-enylmethylcarbamoyl)-4-[2-(6-methyl-2-pyridyl)-7-methoxy-8-methyl-quinolin-4-yloxy]cyclopentanecarbonyl}amino-2-vinylcyclopropanecarboxylic acid ethyl ester (100, 250 mg, 0.37 mmol) was dissolved in dry 1,2-dichloroethane (250 mL). Then, nitrogen gas was bubbled through the solution for 30 min before Hoveyda-Grubbs 2nd generation (25 mg) was added. The resulting solution was refluxed overnight, then cooled down to room temperature and evaporated. The residue was purified by column chromatography on silica gel (gradient AcOEt/Heptane, 3:7 to 5:5) to give 139 mg (58%) of the title compound 101.

Workup

  1. customThen, nitrogen gas was bubbled through the solution for 30 min before Hoveyda-Grubbs 2nd generation (25 mg)
  2. additionwas added
  3. temperatureThe resulting solution was refluxed overnight
  4. customevaporated
  5. customThe residue was purified by column chromatography on silica gel (gradient AcOEt/Heptane, 3:7 to 5:5)

Sources & evidence

ORD record
ord-5c4bf90603d34ea8a80cf86ee2519c63
Source dataset
uspto-grants-2014_06
Patent number
US08754106B2

Reaction notes

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