1-({2-(Hex-5-enyl-methyl-carbamoyl)-4-[2-(4-isopropyl-thiazol-2-yl)-7-methoxy-quinolin-4-yloxy]-cyclopentanecarbonyl}-amino)-2-vinyl-cyclopropanecarboxylic acid ethyl ester → 17-[2-(4-Isopropyl-thiazol-2-yl)-7-methoxy-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 1516668Notes

Reaction equation

HRID 1516668 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](=[CH:25][C:26]([O:30][CH3:31])=[CH:27][CH:28]=4)[N:23]=[C:22]([C:32]4[S:33][CH:34]=[C:35]([CH:37]([CH3:39])[CH3:38])[N:36]=4)[CH:21]=3)[CH2:16][CH:15]2[C:40](=[O:49])[N:41]([CH2:43][CH2:44][CH2:45][CH2:46][CH:47]=C)[CH3:42])=[O:13])[CH2:8][CH:7]1[CH:9]=C)=[O:5])[CH3:2]>ClCCCl>[CH2:1]([O:3][C:4]([C:6]12[CH2:8][CH:7]1[CH:9]=[CH:47][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](=[CH:25][C:26]([O:30][CH3:31])=[CH:27][CH:28]=4)[N:23]=[C:22]([C:32]4[S:33][CH:34]=[C:35]([CH:37]([CH3:39])[CH3:38])[N:36]=4)[CH:21]=3)[CH2:16]1)[C:12](=[O:13])[NH:11]2)=[O:5])[CH3:2]

Participants

3

Reactant 1

HCID 674117151-({2-(Hex-5-enyl-methyl-carbamoyl)-4-[2-(4-isopropyl-thiazol-2-yl)-7-methoxy-quinolin-4-yloxy]-cyclopentanecarbonyl}-amino)-2-vinyl-cyclopropanecarboxylic acid ethyl ester

Product 1

HCID 6741035617-[2-(4-Isopropyl-thiazol-2-yl)-7-methoxy-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 73.3%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

1-({2-(Hex-5-enyl-methyl-carbamoyl)-4-[2-(4-isopropyl-thiazol-2-yl)-7-methoxy-quinolin-4-yloxy]-cyclopentanecarbonyl}-amino)-2-vinyl-cyclopropanecarboxylic acid ethyl ester (33, 280 mg) was dissolved in DCE (280 mL) in a reflux setup. The system was successively evacuated and filled with argon (repeated 3 times). Then, Hoveyda-Grubbs 2nd generation catalyst (28 mg) was added and the system was evacuated and filled with argon twice. The resulting mixture was successively heated to refluxed overnight, concentrated, and subjected to flash column chromatography (silica, AcOEt/hexane) to give 197 mg (73%) of the title product 34 as grey-brown solid: m/z=661 (M+H)+.

Workup

  1. customThe system was successively evacuated
  2. additionfilled with argon (repeated 3 times)
  3. additionThen, Hoveyda-Grubbs 2nd generation catalyst (28 mg) was added
  4. customthe system was evacuated
  5. additionfilled with argon twice
  6. temperatureThe resulting mixture was successively heated
  7. temperatureto refluxed overnight
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-c0a28ce0e5894625aa229670ecb16c01
Source dataset
uspto-grants-2012_07
Patent number
US08227407B2

Reaction notes

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