1-Hydroxybenzotriazole → (2E)-3-[6-(Acetylamino)-3-pyridinyl]-N-[2-[[2,4-dichloro-3-[[(2-methyl-8-quinolinyl)oxy]methyl]phenyl]methylamino]-2-oxoethyl]-2-propenamide

HRID 10759Notes

Reaction equation

HRID 10759 reaction equation
[NH2:1][CH2:2][C:3]([N:5]([C:7]1[C:8]([Cl:27])=[C:9]([C:23]([Cl:26])=[CH:24][CH:25]=1)[CH2:10][O:11][C:12]1[CH:13]=[CH:14][CH:15]=[C:16]2[C:21]=1[N:20]=[C:19]([CH3:22])[CH:18]=[CH:17]2)[CH3:6])=[O:4].[C:28]([NH:31][C:32]1[N:37]=[CH:36][C:35](/[CH:38]=[CH:39]/[C:40](O)=[O:41])=[CH:34][CH:33]=1)(=[O:30])[CH3:29].ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>O.CN(C)C=O>[C:28]([NH:31][C:32]1[N:37]=[CH:36][C:35](/[CH:38]=[CH:39]/[C:40]([NH:1][CH2:2][C:3]([N:5]([C:7]2[C:8]([Cl:27])=[C:9]([C:23]([Cl:26])=[CH:24][CH:25]=2)[CH2:10][O:11][C:12]2[CH:13]=[CH:14][CH:15]=[C:16]3[C:21]=2[N:20]=[C:19]([CH3:22])[CH:18]=[CH:17]3)[CH3:6])=[O:4])=[O:41])=[CH:34][CH:33]=1)(=[O:30])[CH3:29]

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10703461(E)-3-(6-Acetamidopyridin-3-YL)acrylic acidHCID 117954848-[3-(N-glycyl-N-methylamino)2,6-dichlorobenzyloxy]-2-methylquinoline

Product 1

HCID 5311108(2E)-3-[6-(Acetylamino)-3-pyridinyl]-N-[2-[[2,4-dichloro-3-[[(2-methyl-8-quinolinyl)oxy]methyl]phenyl]methylamino]-2-oxoethyl]-2-propenamideYield 53.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of 8-[3-(N-glycyl-N-methylamino)-2,6-dichlorobenzyloxy]-2-methylquinoline (100 mg), (E)-3-(6-acetamidopyridin-3-yl)acrylic acid (56.1 mg) and N,N-dimethylformamide (2 ml) were added 1-hydroxybenzotriazole (43.4 mg) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (56.9 mg) in a nitrogen stream at 0° C., and the resulting mixture was stirred at ambient temperature for 2 hours. The reaction mixture was poured into water, and extracted with chloroform. The organic layer was washed with an aqueous solution of saturated sodium hydrogencarbonate, water and brine successively, and dried over magnesium sulfate, and thereafter the solvent was removed under reduced pressure. The residue was purified by preparative thin-layer chromatography (methanol:dichloromethane=1:10, v/v), and solidified with diethyl ether and ethyl acetate to give 8-[3-[N-[(E)-3-(6-acetamidopyridin-3-yl)acryloylglycyl]-N-methylamino]-2,6-dichlorobenzyloxy]-2methylquinoline (FR173657) (78.8 mg) as a grayish white solid.

Workup

  1. extractionextracted with chloroform
  2. washThe organic layer was washed with an aqueous solution of saturated sodium hydrogencarbonate, water and brine successively
  3. dry with materialdried over magnesium sulfate
  4. customthe solvent was removed under reduced pressure
  5. customThe residue was purified by preparative thin-layer chromatography (methanol

Sources & evidence

ORD record
ord-f4cfd8c165894839adb182360ea432e1
Source dataset
uspto-grants-2006_08
Patent number
US07094899B2

Reaction notes

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