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Bromomethyl 4-methoxyphenyl ketone → 4'-{[6-cyclopropyl-3-[2-(4-methoxyphenyl)-2-oxoethyl]-2,4-dioxo-3,4-dihydrothieno[2,3-d]pyrimidin-1(2H)-yl]methyl}-3'-fluorobiphenyl-2-carbonitrile

HRID 1889361
Notes
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Reaction equation

HRID 1889361 reaction equation
[CH:1]1([C:4]2[S:30][C:7]3[N:8]([CH2:14][C:15]4[CH:20]=[CH:19][C:18]([C:21]5[C:22]([C:27]#[N:28])=[CH:23][CH:24]=[CH:25][CH:26]=5)=[CH:17][C:16]=4[F:29])[C:9](=[O:13])[NH:10][C:11](=[O:12])[C:6]=3[CH:5]=2)[CH2:3][CH2:2]1.Br[CH2:32][C:33]([C:35]1[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[CH:37][CH:36]=1)=[O:34].CN(C)C=O.[H-].[Na+]>C(OCC)(=O)C>[CH:1]1([C:4]2[S:30][C:7]3[N:8]([CH2:14][C:15]4[CH:20]=[CH:19][C:18]([C:21]5[C:22]([C:27]#[N:28])=[CH:23][CH:24]=[CH:25][CH:26]=5)=[CH:17][C:16]=4[F:29])[C:9](=[O:13])[N:10]([CH2:32][C:33]([C:35]4[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[CH:37][CH:36]=4)=[O:34])[C:11](=[O:12])[C:6]=3[CH:5]=2)[CH2:3][CH2:2]1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 4965Bromomethyl 4-methoxyphenyl ketoneHCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 593515214'-[(6-cyclopropyl-2,4-dioxo-3,4-dihydrothieno[2,3-d]pyrimidin-1(2H)-yl)methyl]-3'-fluorobiphenyl-2-carbonitrile

Product 1

HCID 593516504'-{[6-cyclopropyl-3-[2-(4-methoxyphenyl)-2-oxoethyl]-2,4-dioxo-3,4-dihydrothieno[2,3-d]pyrimidin-1(2H)-yl]methyl}-3'-fluorobiphenyl-2-carbonitrile
Yield 47%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 4′-[(6-cyclopropyl-2,4-dioxo-3,4-dihydrothieno[2,3-d]pyrimidin-1(2H)-yl)methyl]-3′-fluorobiphenyl-2-carbonitrile (1.5 g), 2-bromo-1-(4-methoxyphenyl)ethanone (0.99 g) and N,N-dimethylformamide (40 mL) was added 60% sodium hydride (0.17 g), and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with ethyl acetate, washed with 5% potassium hydrogensulfate and then saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give the title compound as colorless crystals (0.95 g, 47%).

Workup

  1. washwashed with 5% potassium hydrogensulfate
  2. dry with materialsaturated brine, and dried over anhydrous magnesium sulfate
  3. customThe solvent was evaporated under reduced pressure
  4. customThe obtained residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-216b55f5bb3947b1aeff8a9c35a6f6ed
Source dataset
uspto-grants-2013_08
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08501750B2

Reaction notes

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