Methyl Acrylate → 2-anilino-6-[(E)-3-methoxy-3-oxo-1-propenyl]-7-methyl-1-phenyl-1,8-naphthyridin-4(1H)-one

HRID 1063567Notes

Reaction equation

[NH:1]([C:8]1[N:9]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:10]2[C:15]([C:16](=[O:18])[CH:17]=1)=[CH:14][C:13](Br)=[C:12]([CH3:20])[N:11]=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[C:46]([O:50][CH3:51])(=[O:49])[CH:47]=[CH2:48]>CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[NH:1]([C:8]1[N:9]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:10]2[N:11]=[C:12]([CH3:20])[C:13](/[CH:48]=[CH:47]/[C:46]([O:50][CH3:51])=[O:49])=[CH:14][C:15]=2[C:16](=[O:18])[CH:17]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 120 °C

Procedure

To a suspension of 2-anilino-6-bromo-7-methyl-1-phenyl-1,8-naphthyridin-4(1H)-one (41 mg, 0.1 mmol) in DMF (2.0 mL) were successively added Pd(OAc)2 (0.70 mg, 0.003 mmol), Ph3P (5.2 mg, 0.02 mmol), TEA (0.03 mL) and methyl acrylate (17.2 mg, 0.2 mmol). The suspension was heated at 120° C. in a sealed tube for 64 h. The residue obtained after concentration in vacuo was washed with water and extracted with EtOAc. The organic layer was dried over MgSO4 and concentrated in vacuo. Purification by prep-HPLC provided methyl (2E)-3-(7-anilino-2-methyl-5-oxo-8-phenyl-5,8-dihydro-1,8-naphthyridin-3-yl)-2-propenoate (10.0 mg, 24%): LCMS RT: 2.61 min, MH+: 412.3, Rη=0.26 (1:1 EtOAc:Hex).

Workup

customThe residue obtained
concentrationafter concentration in vacuo
washwas washed with water
extractionextracted with EtOAc
dry with materialThe organic layer was dried over MgSO4
concentrationconcentrated in vacuo
customPurification

Sources & evidence

ORD record: ord-5ef1118b010c43cfa3281d6bbc3fa053
Source dataset: uspto-grants-2005_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06964971B2

Reaction notes

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