HCID 66870705, compound → HCID 66871634, compound

HRID 531361Notes

Reaction equation

HRID 531361 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]([CH:39]([CH3:41])[CH3:40])[N:34]=4)[CH:21]=3)[CH2:16][CH:15]2[C:42](=[O:51])[N:43]([CH2:45][CH2:46][CH2:47][CH2:48]C=C)[CH3:44])=[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][CH2:48][CH2:47][CH2:46][CH2:45][N:43]([CH3:44])[C:42](=[O:51])[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]([CH:39]([CH3:40])[CH3:41])[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 66870705HCID 66870705, compound

Product 1

HCID 66871634HCID 66871634, compoundYield 66%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

1-{2-(hex-5-enylmethylcarbamoyl)-4-[2-(6-isopropyl-2-pyridyl)-7-methoxy-8-methyl-quinolin-4-yloxy]cyclopentanecarbonyl}amino-2-vinyl-cyclopropanecarboxylic acid ethyl ester (111, 438 mg, 0.50 mmol) was dissolved in dry 1,2-dichloroethane. Then, nitrogen gas was bubbled through the solution for 30 min before Hoveyda-Grubbs 1st generation (15 mg) was added. The resulting solution was refluxed for 3 h, then more catalyst (20 mg) was added. After 2 h at reflux, another 10 mg of the catalyst was added. After 12 h at reflux, the reaction mixture was cooled down to room temperature. Then, scavenger MP-TMT (Agronaut Technologies Inc.) was added (˜300 mg) and the mixture was stirred at room temperature for 45 min. The catalyst was discarded by filtration on silica gel (gradient of CHCl3/MeOH, 1:0 to 98:2) to give 220 mg (66%) of the title compound 112: m/z=669 (M+H)+.

Workup

  1. customThen, nitrogen gas was bubbled through the solution for 30 min before Hoveyda-Grubbs 1st generation (15 mg)
  2. additionwas added
  3. temperatureThe resulting solution was refluxed for 3 h
  4. additionmore catalyst (20 mg) was added
  5. temperatureAfter 2 h at reflux
  6. additionanother 10 mg of the catalyst was added
  7. temperatureAfter 12 h at reflux
  8. additionThen, scavenger MP-TMT (Agronaut Technologies Inc.) was added (˜300 mg)
  9. filtrationThe catalyst was discarded by filtration on silica gel (gradient of CHCl3/MeOH, 1:0 to 98:2)

Sources & evidence

ORD record
ord-22adf6aaea3646579d5ab45f2a3c0019
Source dataset
uspto-grants-2016_05
Patent number
US09353103B2

Reaction notes

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