Hydroxyamine hydrochloride → 3-(5-(5-cyclopropylisoxazol-3-ylamino)-2-methylphenyl)-1,7-dimethyl-1,6-naphthyridin-2(1H)-one

HRID 2061193Notes

Reaction equation

[CH:1]1([C:4](=[O:30])/[CH:5]=[C:6](/[NH:9][C:10]2[CH:11]=[CH:12][C:13]([CH3:29])=[C:14]([C:16]3[C:17](=[O:28])[N:18]([CH3:27])[C:19]4[C:24]([CH:25]=3)=[CH:23][N:22]=[C:21]([CH3:26])[CH:20]=4)[CH:15]=2)\SC)[CH2:3][CH2:2]1.Cl.[NH2:32]O>CN(C=O)C>[CH:1]1([C:4]2[O:30][N:32]=[C:6]([NH:9][C:10]3[CH:11]=[CH:12][C:13]([CH3:29])=[C:14]([C:16]4[C:17](=[O:28])[N:18]([CH3:27])[C:19]5[C:24]([CH:25]=4)=[CH:23][N:22]=[C:21]([CH3:26])[CH:20]=5)[CH:15]=3)[CH:5]=2)[CH2:3][CH2:2]1

Participants

Conditions

Temperature: 100 °C

Procedure

To the above crude mixture of (Z)-3-(5-(3-cyclopropyl-1-(methylthio)-3-oxoprop-1-enylamino)-2-methylphenyl)-1,7-dimethyl-1,6-naphthyridin-2(1H)-one 31 were added hydroxylamine hydrochloride (174 mg, 2.4 mmol) and DMF (2 mL). The resulting mixture was heated at 100° C. for 30 min. The mixture was purified by preparative LC/MS to give 3-(5-(5-cyclopropylisoxazol-3-ylamino)-2-methylphenyl)-1,7-dimethyl-1,6-naphthyridin-2(1H)-one (D4). 1H NMR (400 MHz, d6-DMSO) δ 9.21 (s, 1H), 9.13 (s, 1H), 8.10 (s, 1H), 7.96 (s, 1H), 7.39 (d, J=2.4 Hz, 1H), 7.29 (dd, J=2.4, 8.4 Hz, 1H), 7.19 (d, J=8.4 Hz, 1H), 5.83 (s, 1H), 3.72 (s, 3H), 2.79 (s, 3H), 2.07 (s, 3H), 2.05 (m, 1H), 1.01 (m, 2H), 0.84 (m, 2H). MS m/z 387.2 (M+1).

Workup

customThe mixture was purified by preparative LC/MS

Sources & evidence

ORD record: ord-966a530d819d40ed81b87f44841d08c0
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08278452B2

Reaction notes

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