Chloroform → 2-(4-Hydroxy-1-methyl-2-oxo-6-(piperidin-1-yl)-1,2-dihydroquinoline-3-carboxamido)acetic acid

HRID 905906Notes

Reaction equation

[OH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9](I)[CH:10]=2)[N:5]([CH3:13])[C:4](=[O:14])[C:3]=1[C:15]([NH:17][CH2:18][C:19]([O:21]CC)=[O:20])=[O:16].C(Cl)(Cl)Cl.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.CC(C)([O-])C.[Na+].[NH:68]1[CH2:73][CH2:72][CH2:71][CH2:70][CH2:69]1>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[OH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([N:68]3[CH2:73][CH2:72][CH2:71][CH2:70][CH2:69]3)[CH:10]=2)[N:5]([CH3:13])[C:4](=[O:14])[C:3]=1[C:15]([NH:17][CH2:18][C:19]([OH:21])=[O:20])=[O:16]

Participants

Conditions

Temperature: 80 °C

Procedure

A solution of ethyl 2-(4-hydroxy-6-iodo-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamido)acetate (250 mg, 581 μmol), Pd2dba3.CHCl3 (60 mg, 58 μmol), X-Phos (55 mg 116 μmol) and sodium t-butoxide (279 mg, 2906 μmol) in 1,4-dioxane (5 ml) was treated with piperidine (287 μl, 2906 μmol). The reaction was stirred at 80° C. in a sealed tube. After 22 hours, the solution was cooled to 23° C., filtered through celite (washing with MeOH), concentrated, diluted with methanol/DMSO and purified by RP HPLC (0-100% MeCN/water+1% TFA, 10 min), affording 17 mg (8%) of 2-(4-hydroxy-1-methyl-2-oxo-6-(piperidin-1-yl)-1,2-dihydroquinoline-3-carboxamido)acetic acid as an off-white solid.

Workup

temperaturethe solution was cooled to 23° C.
filtrationfiltered through celite (washing with MeOH)
concentrationconcentrated
additiondiluted with methanol/DMSO
custompurified by RP HPLC (0-100% MeCN/water+1% TFA, 10 min)

Sources & evidence

ORD record: ord-f952f429f2c84c15b8c31f0f66e9de19
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08012968B2

Reaction notes

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