Tetrahydrofuran → 4'-{[6-ethyl-3-[2-(4-methoxy-3-methylphenyl)-2-oxoethyl]-2,4-dioxo-3,4-dihydrothieno[2,3-d]pyrimidin-1(2H)-yl]methyl}biphenyl-2-carbonitrile

HRID 1889359Notes

Reaction equation

HRID 1889359 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:10](=[O:40])[CH2:11][N:12]2[C:17](=[O:18])[C:16]3[CH:19]=[C:20]([CH2:22][CH3:23])[S:21][C:15]=3[N:14]([CH2:24][C:25]3[CH:30]=[CH:29][C:28]([C:31]4[C:32]([C:37]#[N:38])=[CH:33][CH:34]=[CH:35][CH:36]=4)=[CH:27][CH:26]=3)[C:13]2=[O:39])[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].[CH3:41]B(O)O.C(=O)([O-])[O-].[K+].[K+].O1CCCC1>C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[CH2:22]([C:20]1[S:21][C:15]2[N:14]([CH2:24][C:25]3[CH:26]=[CH:27][C:28]([C:31]4[C:32]([C:37]#[N:38])=[CH:33][CH:34]=[CH:35][CH:36]=4)=[CH:29][CH:30]=3)[C:13](=[O:39])[N:12]([CH2:11][C:10]([C:4]3[CH:5]=[CH:6][C:7]([O:8][CH3:9])=[C:2]([CH3:41])[CH:3]=3)=[O:40])[C:17](=[O:18])[C:16]=2[CH:19]=1)[CH3:23]

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 139377Methylboronic AcidHCID 593516184'-{[3-[2-(3-bromo-4-methoxyphenyl)-2-oxoethyl]-6-ethyl-2,4-dioxo-3,4-dihydrothieno[2,3-d]pyrimidin-1(2H)-yl]methyl}biphenyl-2-carbonitrile

Product 1

HCID 593516474'-{[6-ethyl-3-[2-(4-methoxy-3-methylphenyl)-2-oxoethyl]-2,4-dioxo-3,4-dihydrothieno[2,3-d]pyrimidin-1(2H)-yl]methyl}biphenyl-2-carbonitrileYield 81%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 4′-{[3-[2-(3-bromo-4-methoxyphenyl)-2-oxoethyl]-6-ethyl-2,4-dioxo-3,4-dihydrothieno[2,3-d]pyrimidin-1(2H)-yl]methyl}biphenyl-2-carbonitrile (1.3 g), methylboronic acid (0.25 g), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (0.086 g), potassium carbonate (0.88 g), tetrahydrofuran (50 mL) and water (5 mL) was stirred under argon atmosphere at 50° C. for 2 days. The reaction mixture was diluted with ethyl acetate, and insoluble material was filtered off through celite. The filtrate was concentrated under reduced pressure and the obtained residue was purified by silica gel column chromatography to give the title compound as a colorless amorphous solid (0.94 g, 81%).

Workup

  1. filtrationwas filtered off through celite
  2. concentrationThe filtrate was concentrated under reduced pressure
  3. customthe obtained residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-9d14606401814237934ab81cd0eae2b2
Source dataset
uspto-grants-2013_08
Patent number
US08501750B2

Reaction notes

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