Triphenylphosphine → 2-(1-Ethoxycarbonyl-2-vinylcyclopropylcarbamoyl)-4-[2-(6-methyl-2-pyridyl)-7-methoxy-8-methylquinolin-4-yloxy]cyclopentanecarboxylic acid tert-butyl ester

HRID 402167Notes

Reaction equation

HRID 402167 reaction equation
[C:1]([O:5][C:6]([CH:8]1[CH2:12][CH:11]([OH:13])[CH2:10][CH:9]1[C:14](=[O:26])[NH:15][C:16]1([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:18][CH:17]1[CH:19]=[CH2:20])=[O:7])([CH3:4])([CH3:3])[CH3:2].O[C:28]1[C:37]2[C:32](=[C:33]([CH3:40])[C:34]([O:38][CH3:39])=[CH:35][CH:36]=2)[N:31]=[C:30]([C:41]2[CH:46]=[CH:45][CH:44]=[C:43]([CH3:47])[N:42]=2)[CH:29]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[C:1]([O:5][C:6]([CH:8]1[CH2:12][CH:11]([O:13][C:28]2[C:37]3[C:32](=[C:33]([CH3:40])[C:34]([O:38][CH3:39])=[CH:35][CH:36]=3)[N:31]=[C:30]([C:41]3[CH:46]=[CH:45][CH:44]=[C:43]([CH3:47])[N:42]=3)[CH:29]=2)[CH2:10][CH:9]1[C:14](=[O:26])[NH:15][C:16]1([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:18][CH:17]1[CH:19]=[CH2:20])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 668714182-(1-Ethoxycarbonyl-2-vinylcyclopropylcarbamoyl)-4-hydroxycyclopentanecarboxylic acid tert-butyl esterHCID 178487678HCID 178487678, compound

Product 1

HCID 668713072-(1-Ethoxycarbonyl-2-vinylcyclopropylcarbamoyl)-4-[2-(6-methyl-2-pyridyl)-7-methoxy-8-methylquinolin-4-yloxy]cyclopentanecarboxylic acid tert-butyl esterYield 116.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2-(1-ethoxycarbonyl-2-vinylcyclopropylcarbamoyl)-4-hydroxycyclo-pentanecarboxylic acid tert-butyl ester (500 mg, 1.5 mmol), prepared as described in WO2005/073195, 4-hydroxy-2-(6-methyl-2-pyridyl)-7-methoxy-8-methylquinoline (97, 504 mg, 1.8 mmol) and triphenylphosphine (990 mg, 3.75 mmol) were stirred in dry THF (40 mL) at 0° C. for 10 min. Then, DIAD (0.74 mL, 3.75 mmol) was added drop wise. The resulting reaction mixture was stirred at a temperature from 0° C. to 22° C. overnight. Then, volatiles were evaporated and the residue was purified by column chromatography on silica gel (gradient CH2Cl2/AcOEt, 1:0 to 95:5) to give 1.1 g (88%) of the title compound 98: m/z=630 (M+H)+.

Workup

  1. customThe resulting reaction mixture
  2. customThen, volatiles were evaporated
  3. customthe residue was purified by column chromatography on silica gel (gradient CH2Cl2/AcOEt, 1:0 to 95:5)

Sources & evidence

ORD record
ord-9f96f833085144e49b4bab8c6e97a739
Source dataset
uspto-grants-2014_06
Patent number
US08741926B2

Reaction notes

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