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

HRID 2061190Notes

Reaction equation

[CH3:1][N:2]1[C:11]2[C:6](=[CH:7][N:8]=[C:9]([CH3:12])[CH:10]=2)[CH:5]=[C:4]([C:13]2[CH:18]=[C:17]([NH:19]/[C:20](/SC)=[CH:21]/[C:22](=[O:28])[C:23]3[S:24][CH:25]=[CH:26][N:27]=3)[CH:16]=[CH:15][C:14]=2[CH3:31])[C:3]1=[O:32].O1CCCCC1O[NH2:40].C([O-])([O-])=O.[K+].[K+]>O1CCOCC1>[CH3:1][N:2]1[C:11]2[C:6](=[CH:7][N:8]=[C:9]([CH3:12])[CH:10]=2)[CH:5]=[C:4]([C:13]2[CH:18]=[C:17]([NH:19][C:20]3[CH:21]=[C:22]([C:23]4[S:24][CH:25]=[CH:26][N:27]=4)[O:28][N:40]=3)[CH:16]=[CH:15][C:14]=2[CH3:31])[C:3]1=[O:32]

Participants

Conditions

Temperature: 150 °C

Procedure

The mixture of (Z)-1,7-dimethyl-3-(2-methyl-5-(1-(methylthio)-3-oxo-3-(thiazol-2-yl)prop-1-enylamino)phenyl)-1,6-naphthyridin-2(1H)-one 32 (462 mg, 1.0 mmol), O-(tetrahydro-2H-pyran-2-yl)hydroxylamine (293 mg, 2.5 mmol) and K2CO3 (415 mg, 3.0 mmol) in 1,4-dioxane (5 mL) in a sealed vial was heated at 150° C. for 30 h. The mixture was purified by preparative LC/MS to give 1,7-dimethyl-3-(2-methyl-5-(5-(thiazol-2-yl)isoxazol-3-ylamino)phenyl)-1,6-naphthyridin-2(1H)-one (D9). 1H NMR (400 MHz, d6-DMSO) δ 10.73 (s, 1H), 9.19 (s, 1H), 8.11 (s, 1H), 7.93 (s, 1H), 7.87 (d, J=3.2 Hz, 1H), 7.74 (d, J=3.2 Hz, 1H), 7.65 (d, J=2.4 Hz, 1H), 7.61 (s, 1H), 7.53 (dd, J=2.4, 8.0 Hz, 1H), 7.27 (d, J=8.0 Hz, 1H), 3.72 (s, 3H), 2.78 (s, 3H), 2.10 (s, 3H). MS m/z 430.2 (M+1).

Workup

customThe mixture was purified by preparative LC/MS

Sources & evidence

ORD record: ord-79a7d6ce2e83492490c2c54ffd151280
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08278452B2

Reaction notes

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