Acetic Acid → 7-Chloro-3-(3,5-dimethylphenyl)-4-hydroxy-2-oxo-1,2-dihydroquinoline-6-carboxylic acid pyrimidin-4-ylamide

HRID 1858110Notes

Reaction equation

CS(C)=O.[Cl:5][C:6]1[CH:15]=[C:14]2[C:9]([C:10]([OH:25])=[C:11]([C:17]3[CH:22]=[C:21]([CH3:23])[CH:20]=[C:19]([CH3:24])[CH:18]=3)[C:12](=[O:16])[NH:13]2)=[CH:8][C:7]=1I.[NH2:27][C:28]1[CH:33]=[CH:32][N:31]=[CH:30][N:29]=1.[C:34](O)(=[O:36])C>CN(C)C1C=CN=CC=1.Cl[Pd]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[N:31]1[CH:32]=[CH:33][C:28]([NH:27][C:34]([C:7]2[CH:8]=[C:9]3[C:14](=[CH:15][C:6]=2[Cl:5])[NH:13][C:12](=[O:16])[C:11]([C:17]2[CH:22]=[C:21]([CH3:23])[CH:20]=[C:19]([CH3:24])[CH:18]=2)=[C:10]3[OH:25])=[O:36])=[N:29][CH:30]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To 20 mL dry methylsulfoxide was added sequentially 7-chloro-3-(3,5-dimethylphenyl)-4-hydroxy-6-iodo-1H-quinolin-2-one (EXAMPLE 4.2 Step B, 1.0 g), 4-dimethylaminopyridine (860 mg), 4-aminopyrimidine (90 mg), [1,1'-bis(diphenylphosphino)ferrocene)-dichloropalladium (II) and the mixture heated to 100° C. under an atmosphere of carbon monoxide. After 72 hours, the mixture was cooled to room temperature and poured into 200 mL ice/water. The pH of the resulting solution was adjusted to pH4 by the addition of acetic acid. The resulting solids were collected by filtration and then re-purified by flash chromatography on silica gel (chlorofonm:methanol, 95:5) to give the title compound (400 mg).

Workup

temperaturethe mixture was cooled to room temperature
filtrationThe resulting solids were collected by filtration
customre-purified by flash chromatography on silica gel (chlorofonm:methanol, 95:5)

Sources & evidence

ORD record: ord-dfc0be174c404b838de58a80a4e9758b
Source dataset: uspto-grants-2000_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06150352

Reaction notes

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