Cesium carbonate → 5-Bromo-3-(6,6-dimethyl-6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-2-ylamino)-1-methylpyridin-2(1H)-one

HRID 593176Notes

Reaction equation

[CH3:1][C:2]1([CH3:12])[O:7][CH2:6][C:5]2=[CH:8][C:9]([NH2:11])=[N:10][N:4]2[CH2:3]1.Br[C:14]1[C:15](=[O:22])[N:16]([CH3:21])[CH:17]=[C:18]([Br:20])[CH:19]=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:20][C:18]1[CH:19]=[C:14]([NH:11][C:9]2[CH:8]=[C:5]3[CH2:6][O:7][C:2]([CH3:12])([CH3:1])[CH2:3][N:4]3[N:10]=2)[C:15](=[O:22])[N:16]([CH3:21])[CH:17]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A 100-mL round-bottomed flask equipped with a reflux condenser was charged with 1,4-dioxane (10 mL), 6,6-dimethyl-6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-2-amine 330g (167 mg, 1.0 mmol), 3,5-dibromo-1-methylpyridin-2(1H)-one (320 mg, 1.2 mmol), Pd2(dba)3 (91 mg, 0.10 mmol), XantPhos (116 mg, 0.20 mmol), and cesium carbonate (652 mg, 2.0 mmol). After three cycles of vacuum/argon flush, the mixture was heated at 100° C. for 3 h. It was then filtered and the filtrate was evaporated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with 100:1 dichloromethane/methanol to afford 335a (210 mg, 60%) as a yellow solid. MS-ESI: [M+H]+ 352.9

Workup

customA 100-mL round-bottomed flask equipped with a reflux condenser
customAfter three cycles of vacuum/argon flush
filtrationIt was then filtered
customthe filtrate was evaporated under reduced pressure
customThe residue was purified by silica-gel column chromatography
washeluting with 100:1 dichloromethane/methanol

Sources & evidence

ORD record: ord-de9f309d48f84df8a8df2882841dec95
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09238655B2

Reaction notes

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