Diisopropylethylamine → 1-{2-(Hex-5-enylmethylcarbamoyl)-4-[2-(6-methyl-2-pyridyl)-7-methoxy-8-methylquinolin-4-yloxy]cyclopentanecarbonyl}amino-2-vinylcyclopropanecarboxylic acid ethyl ester

HRID 1803692Notes

Reaction equation

HRID 1803692 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(C4C=CC=C(C)N=4)[CH:21]=3)[CH2:16][CH:15]2[C:40](O)=[O:41])=[O:13])[CH2:8][CH:7]1[CH:9]=[CH2:10])=[O:5])[CH3:2].Cl.[CH3:44][NH:45][CH2:46][CH2:47][CH2:48][CH2:49][CH:50]=[CH2:51].[CH:52]([N:55]([CH:58]([CH3:60])[CH3:59])CC)([CH3:54])[CH3:53].[CH3:61]N(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[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:60]([C:58]4[CH:59]=[CH:61][CH:54]=[C:52]([CH3:53])[N:55]=4)[CH:21]=3)[CH2:16][CH:15]2[C:40](=[O:41])[N:45]([CH2:46][CH2:47][CH2:48][CH2:49][CH:50]=[CH2:51])[CH3:44])=[O:13])[CH2:8][CH:7]1[CH:9]=[CH2:10])=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 668720342-(1-Ethoxycarbonyl-2-vinylcyclopropylcarbamoyl)-4-[2-(6-methyl-2-pyridyl)-7-methoxy-8-methylquinolin-4-yloxy]cyclopentanecarboxylic acidHCID 71413963N-Methylhex-5-en-1-amine hydrochloride

Product 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 esterYield 82%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 2-(1-ethoxycarbonyl-2-vinylcyclopropylcarbamoyl)-4-[2-(6-methyl-2-pyridyl)-7-methoxy-8-methylquinolin-4-yloxy]cyclopentanecarboxylic acid (99, 0.77 g, 1.344 mmol), N-methylhex-5-enylamine hydrochloride (221 mg, 1.95 mmol) and diisopropylethylamine (1.17 mL, 6.72 mmol) in DMF (25 mL) was stirred at 0° C. under inert atmosphere. After 30 min HATU (741 mg, 1.95 mmol) was added and the reaction mixture was allowed to warm up to room temperature overnight. Then, DMF was evaporated and the residue was partitioned between AcOEt and a solution of NaHCO3. Organic layer was successively washed with water and brine, dried (MgSO4), filtered and evaporated. The crude product was purified by silica gel chromatography (gradient Heptane/AcOEt 80:20 to 50:50) to give 735 mg (82%) of the title compound: m/z=669 (M+H)+.

Workup

  1. customThen, DMF was evaporated
  2. customthe residue was partitioned between AcOEt
  3. washOrganic layer was successively washed with water and brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated
  7. customThe crude product was purified by silica gel chromatography (gradient Heptane/AcOEt 80:20 to 50:50)

Sources & evidence

ORD record
ord-460d5929036642f89ac5056fdc6c8e6b
Source dataset
uspto-grants-2013_01
Patent number
US08349869B2

Reaction notes

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