Potassium Hydroxide → 1,7-dimethyl-3-(2-methyl-5-(3-(thiazol-2-yl)isoxazol-5-ylamino)phenyl)-1,6-naphthyridin-2(1H)-one

HRID 2061194Notes

Reaction equation

Cl.[NH2:2][OH:3].[OH-].[K+].[CH3:6][N:7]1[C:16]2[C:11](=[CH:12][N:13]=[C:14]([CH3:17])[CH:15]=2)[CH:10]=[C:9]([C:18]2[CH:23]=[C:22]([NH:24]/[C:25](/SC)=[CH:26]/[C:27](=O)[C:28]3[S:29][CH:30]=[CH:31][N:32]=3)[CH:21]=[CH:20][C:19]=2[CH3:36])[C:8]1=[O:37].CC[O-].[Na+]>CCO>[CH3:6][N:7]1[C:16]2[C:11](=[CH:12][N:13]=[C:14]([CH3:17])[CH:15]=2)[CH:10]=[C:9]([C:18]2[CH:23]=[C:22]([NH:24][C:25]3[O:3][N:2]=[C:27]([C:28]4[S:29][CH:30]=[CH:31][N:32]=4)[CH:26]=3)[CH:21]=[CH:20][C:19]=2[CH3:36])[C:8]1=[O:37]

Participants

Conditions

Temperature: 80 °C

Procedure

To the mixture of hydroxylamine hydrochloride (42 mg, 0.6 mmol) and KOH (34 mg, 0.6 mmol) in EtOH (2 mL) was added the crude (Z)-1,7-dimethyl-3-(2-methyl-5-(1-(methylthio)-3-oxo-3-(thiazol-2-yl)prop-1-enyl amino)phenyl)-1,6-naphthyridin-2(1H)-one 32. The resulting mixture was heated at 80° C. for 30 min. Then NaOEt (40.8 mg, 0.6 mmol) was added and the reaction mixture was refluxed for 1 h. The mixture was purified by preparative LC/MS to give 1,7-dimethyl-3-(2-methyl-5-(3-(thiazol-2-yl)isoxazol-5-ylamino)phenyl)-1,6-naphthyridin-2(1H)-one (F1). 1H NMR (400 MHz, d6-DMSO) δ 9.50 (s, 1H), 9.13 (s, 1H), 7.95-8.10 (m, 3H), 7.88 (s, 1H), 7.38 (s, 1H), 7.30 (d, J=8.0 Hz, 1H), 7.18 (d, J=8.0 Hz, 1H), 6.94 (s, 1H), 3.65 (s, 1H), 2.72 (s, 3H), 2.03 (s, 3H). MS m/z 430.1 (M+1).

Workup

temperaturethe reaction mixture was refluxed for 1 h
customThe mixture was purified by preparative LC/MS

Sources & evidence

ORD record: ord-65534b92922b4f388efe9f6c177cc7d3
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08278452B2

Reaction notes

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