Cesium carbonate → 5-Bromo-1-methyl-3-(pyrazin-2-ylamino)pyridin-2(1H)-one

HRID 1411653Notes

Reaction equation

[N:1]1[CH:6]=[CH:5][N:4]=[CH:3][C:2]=1[NH2:7].Br[C:9]1[C:10](=[O:17])[N:11]([CH3:16])[CH:12]=[C:13]([Br:15])[CH:14]=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:15][C:13]1[CH:14]=[C:9]([NH:7][C:2]2[CH:3]=[N:4][CH:5]=[CH:6][N:1]=2)[C:10](=[O:17])[N:11]([CH3:16])[CH:12]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with pyrazin-2-amine (500 mg, 5.3 mmol), 3,5-dibromo-1-methylpyridin-2(1H)-one (1335 mg, 5.3 mmol), Pd2(dba)3 (229 mg, 0.25 mmol), XantPhos (289 mg, 0.50 mmol), cesium carbonate (3.26 g, 10 mmol) and 1,4-dioxane (50 mL). After three cycles of vacuum/argon flush, the mixture was stirred at 100° C. for 2 h. It was then filtered and the filtrate was evaporated in vacuo. The residue was purified by silica-gel column chromatography eluting with 50:1 dichloromethane/methanol to afford 162a (420 mg, 30%) as a yellow solid. MS-ESI: [M+H]+ 281.0.

Workup

customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
customAfter three cycles of vacuum/argon flush
filtrationIt was then filtered
customthe filtrate was evaporated in vacuo
customThe residue was purified by silica-gel column chromatography
washeluting with 50:1 dichloromethane/methanol

Sources & evidence

ORD record: ord-c9470feeee7d4f9cbdbbe8d31f379bb0
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08921353B2

Reaction notes

Loading…