Lithium Hydroxide → 2-[1-(4-(Ethoxycarbonyl)piperazin-1-yl)carbonyl-3-carboxypropyl]aminocarbonyl-4-chloroquinoline

HRID 348090Notes

Reaction equation

HRID 348090 reaction equation
[CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][N:9]([C:12]([CH:14]([NH:21][C:22]([C:24]2[CH:33]=[C:32]([Cl:34])[C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[N:25]=2)=[O:23])[CH2:15][CH2:16][C:17]([O:19]C)=[O:18])=[O:13])[CH2:8][CH2:7]1)=[O:5])[CH3:2].[Li+].[OH-]>C1COCC1>[CH2:1]([O:3][C:4]([N:6]1[CH2:7][CH2:8][N:9]([C:12]([CH:14]([NH:21][C:22]([C:24]2[CH:33]=[C:32]([Cl:34])[C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[N:25]=2)=[O:23])[CH2:15][CH2:16][C:17]([OH:19])=[O:18])=[O:13])[CH2:10][CH2:11]1)=[O:5])[CH3:2]

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 220173792-[1-(4-(Ethoxycarbonyl)piperazin-1-yl)carbonyl-3-(methoxycarbonyl)propyl]aminocarbonyl-4-chloroquinoline

Product 1

HCID 220173642-[1-(4-(Ethoxycarbonyl)piperazin-1-yl)carbonyl-3-carboxypropyl]aminocarbonyl-4-chloroquinolineYield 111.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 4-ethoxycarbonyl-1-(1-amino-3-(methoxycarbonyl)propyl)carbonylpiperazine (0.97 g, 3.23 mmol), 2-carboxy-4-chloroquinoline (0.67 g, 3.23 mmol), EDCl (0.68 g, 3.55 mmol) and HOBT (0.48 g, 3.55 mmol) was combined in 30 mL of THF. The reaction mixture was stirred overnight at ambient temperature. The reaction was diluted with ethyl acetate and washed with water. The organic layer was concentrated to give a dark oil (0.87 g) that was purified by flash chromotography through silica gel with 2:1 ethyl acetate-hexanes to provide 2-[1-(4-(ethoxycarbonyl)piperazin-1-yl)carbonyl-3-(methoxycarbonyl)propyl]aminocarbonyl-4-chloroquinoline (0.46 g). A solution of 2-[1-(4-(ethoxycarbonyl)piperazin-1-yl)carbonyl-3-(methoxycarbonyl)propyl]aminocarbonyl-4-chloroquinoline (0.15 g, 0.313 mmol) was dissolved in 5 mL THF and LiOH (0.25 M, 1.9 mL, 0.47 mmol) was added. The reaction mixture was stirred for 2 hours. The reaction mixture was concentrated to an oil, acidified with 10% HCl, extracted into ethyl acetate, and concentrated to provide pure 2-[1-(4-(ethoxycarbonyl)piperazin-1-yl)carbonyl-3-carboxypropyl]aminocarbonyl-4-chloroquinoline, (167 mg); NMR 1.20 (t, 3), 1.90 (m, 1), 2.05 (m, 1), 2.35 (m, 2), 3.35–3.60 (m, 8), 3.65 (m, 2), 4.05 (q, 2), 5.07 (m, 1), 7.95 (m, 1), 8.02 (m, 1), 8.23 (s, 1), 8.30 (m, 1), 8.98 (m, 1) ppm.

Workup

  1. concentrationThe reaction mixture was concentrated to an oil
  2. extractionextracted into ethyl acetate
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-b20be6a3296b4d98aa814332a5e1ca10
Source dataset
uspto-grants-2007_02
Patent number
US07176207B2

Reaction notes

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