Cesium carbonate → 5-Bromo-3-(5-ethylisoxazol-3-ylamino)-1-methylpyridin-2(1H)-one

HRID 1185229Notes

Reaction equation

[CH2:1]([C:3]1[O:7][N:6]=[C:5]([NH2:8])[CH:4]=1)[CH3:2].Br[C:10]1[C:11](=[O:18])[N:12]([CH3:17])[CH:13]=[C:14]([Br:16])[CH:15]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[Br:16][C:14]1[CH:15]=[C:10]([NH:8][C:5]2[CH:4]=[C:3]([CH2:1][CH3:2])[O:7][N:6]=2)[C:11](=[O:18])[N:12]([CH3:17])[CH:13]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A 50-mL single-neck round-bottomed flask equipped with a magnetic stirred and a reflux condenser was charged with 5-ethylisoxazol-3-amine (250 mg, 2.23 mmol), 3,5-dibromo-1-methylpyridin-2(1H)-one (893 mg, 3.35 mmol), Pd2(dba)3 (102 mg, 0.112 mmol), Xantphos (129 mg, 0.223 mmol), Cs2CO3 (1.45 g, 4.46 mmol), and dioxane (20 mL). The system was subjected to three cycles of vacuum/nitrogen flush and heated at 100° C. under N2 protection for 3 h. Analysis of the reaction mixture by LCMS showed complete conversion to the desired product. It was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by reverse-phase prep-HPLC to afford 158a (300 mg, 45%) as a white solid. MS-ESI: [M+H]+ 297.8

Workup

customA 50-mL single-neck round-bottomed flask equipped with
customflush
temperatureIt was then cooled to room temperature
filtrationfiltered
concentrationThe filtrate was concentrated under reduced pressure
customthe residue was purified by reverse-phase prep-HPLC

Sources & evidence

ORD record: ord-a8eafb7a4992458fbfe70a781718c6d2
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08669251B2

Reaction notes

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