1-Hydroxybenzotriazole → (E)-3-(6-acetamidopyridin-3-yl)-N-[2-[2,4-dichloro-N-methyl-3-[(2-methylquinolin-8-yl)oxymethyl]anilino]-2-oxoethyl]prop-2-enamide

HRID 1635600Notes

Reaction equation

HRID 1635600 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(E)-3-(6-acetamidopyridin-3-yl)-N-[2-[2,4-dichloro-N-methyl-3-[(2-methylquinolin-8-yl)oxymethyl]anilino]-2-oxoethyl]prop-2-enamideYield 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-hydroxy-benzotriazole (43.4 mg) and 1-ethyl-3-(3-dimethylamino-propyl)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)acryloyl-glycyl]-N-methylamino]-2,6-dichlorobenzyloxy]-2-methyl-quinoline (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-246468920e4a40358f9080d502dabd02
Source dataset
uspto-grants-2003_01
Patent number
US06509468B1

Reaction notes

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