Cesium carbonate → tert-butyl 4-[6-(4-fluoro-2-methoxyphenyl)-2,4-dioxo-1,4-dihydrothieno[3,2-d]pyrimidin-3(2H)-yl]piperidine-1-carboxylate

HRID 1476627Notes

Reaction equation

HRID 1476627 reaction equation
Br[C:2]1[S:10][C:9]2[C:8](=[O:11])[N:7]([CH:12]3[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]3)[C:6](=[O:25])[NH:5][C:4]=2[CH:3]=1.[F:26][C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[C:29]([O:36][CH3:37])[CH:28]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>COCCOC.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.Cl[Pd]Cl>[F:26][C:27]1[CH:32]=[CH:31][C:30]([C:2]2[S:10][C:9]3[C:8](=[O:11])[N:7]([CH:12]4[CH2:13][CH2:14][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:16][CH2:17]4)[C:6](=[O:25])[NH:5][C:4]=3[CH:3]=2)=[C:29]([O:36][CH3:37])[CH:28]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 2782672(4-Fluoro-2-methoxyphenyl)boronic acidHCID 67258027tert-butyl 4-(6-bromo-2,4-dioxo-1,4-dihydrothieno[3,2-d]pyrimidin-3(2H)-yl)piperidine-1-carboxylate

Product 1

HCID 67259586tert-butyl 4-[6-(4-fluoro-2-methoxyphenyl)-2,4-dioxo-1,4-dihydrothieno[3,2-d]pyrimidin-3(2H)-yl]piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 11050900Dichlorobis(tricyclohexylphosphine)pallium (II)CatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

Tert-butyl 4-(6-bromo-2,4-dioxo-1,4-dihydrothieno[3,2-d]pyrimidin-3(2H)-yl)piperidine-1-carboxylate (3.00 g, compound B53), (4-fluoro-2-methoxyphenyl)boronic acid (1.30 g) and dichlorobis(tricyclohexylphosphine)palladium (257 mg) are reacted in the presence of aqueous cesium carbonate solution (5.23 ml, 2.0 M) in DME (12 ml) according to the procedure described in example B55. The reaction mixture is poured into ice-cold water and the mixture is extracted with DCM. The organic layer is washed with saturated aqueous sodium chloride solution and filtered using a phase separator. All volatile materials are removed in vacuo to yield the title compound as a solid.

Workup

  1. additionThe reaction mixture is poured into ice-cold water
  2. extractionthe mixture is extracted with DCM
  3. washThe organic layer is washed with saturated aqueous sodium chloride solution
  4. filtrationfiltered
  5. customAll volatile materials are removed in vacuo

Sources & evidence

ORD record
ord-f939fb47fab84845acc56cbca6ab6469
Source dataset
uspto-grants-2015_04
Patent number
US09018175B2

Reaction notes

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