2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)-N-(3-(1,1,1-trifluoro-2-methylpropan-2-yl)isoxazol-5-yl)acetamide → 2-[4-(5-ethoxy-6-oxo-1H-pyridin-3-yl)-2-fluorophenyl]-N-[3-(1,1,1-trifluoro-2-methylpropan-2-yl)-1,2-oxazol-5-yl]acetamide

HRID 1050115Notes

Reaction equation

[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C:20]2[CH:25]=[CH:24][C:23]([CH2:26][C:27]([NH:29][C:30]3[O:34][N:33]=[C:32]([C:35]([CH3:41])([CH3:40])[C:36]([F:39])([F:38])[F:37])[CH:31]=3)=[O:28])=[C:22]([F:42])[CH:21]=2)[CH:7]=[N:8][C:9]=1[O:10]CC1C=CC(OC)=CC=1)[CH3:2]>C(O)(C(F)(F)F)=O>[CH2:1]([O:3][C:4]1[C:9](=[O:10])[NH:8][CH:7]=[C:6]([C:20]2[CH:25]=[CH:24][C:23]([CH2:26][C:27]([NH:29][C:30]3[O:34][N:33]=[C:32]([C:35]([CH3:41])([CH3:40])[C:36]([F:38])([F:39])[F:37])[CH:31]=3)=[O:28])=[C:22]([F:42])[CH:21]=2)[CH:5]=1)[CH3:2]

Participants

Conditions

Temperature: 25 °C

Procedure

A mixture of 2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)-N-(3-(1,1,1-trifluoro-2-methylpropan-2-yl)isoxazol-5-yl)acetamide (100 mg, 0.170 mmol) and TFA (10% in DCM, 100 mL) was stirred at 25° C. for 2 h. The mixture was then concentrated. The crude material was purified by preparative HPLC (MeCN/H2O as eluants, acid condition) to give a white solid of 2-(4-(5-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)-N-(3-(1,1,1-trifluoro-2-methylpropan-2-yl)isoxazol-5-yl)acetamide (28.35 mg, 0.060 mmol, 36% yield): 1H NMR (400 MHz, CD3OD) δ 7.45-7.30 (m, 4H), 7.25 (d, J=1.6 Hz, 1H), 6.36 (s, 1H), 4.12 (q, J=6.8 Hz, 2H), 3.82 (s, 2H), 1.52 (s, 6H), 1.46 (t, J=6.8 Hz, 3H); ES-LCMS m/z 468 (M+H).

Workup

concentrationThe mixture was then concentrated
customThe crude material was purified by preparative HPLC (MeCN/H2O as eluants, acid condition)

Sources & evidence

ORD record: ord-17e57477abc848579baabb67c4d1d4b5
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09382238B2

Reaction notes

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