1,2-Dimethoxyethane → tert-butyl 4-[6-(1,3-benzodioxol-5-yl)-1-[(2-ethyl-2H-tetrazol-5-yl)methyl]-2,4-dioxo-1,4-dihydrothieno[3,2-d]pyrimidin-3(2H)-yl]piperidine-1-carboxylate

HRID 1476619Notes

Reaction equation

HRID 1476619 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])[N:5]([CH2:26][C:27]3[N:28]=[N:29][N:30]([CH2:32][CH3:33])[N:31]=3)[C:4]=2[CH:3]=1.[O:34]1[C:38]2[CH:39]=[CH:40][C:41](B(O)O)=[CH:42][C:37]=2[O:36][CH2:35]1.C(=O)([O-])[O-].[Cs+].[Cs+].COCCOC>C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.Cl[Pd]Cl.C(Cl)Cl.O>[O:34]1[C:38]2[CH:39]=[CH:40][C:41]([C:2]3[S:10][C:9]4[C:8](=[O:11])[N:7]([CH:12]5[CH2:13][CH2:14][N:15]([C:18]([O:20][C:21]([CH3:23])([CH3:22])[CH3:24])=[O:19])[CH2:16][CH2:17]5)[C:6](=[O:25])[N:5]([CH2:26][C:27]5[N:28]=[N:29][N:30]([CH2:32][CH3:33])[N:31]=5)[C:4]=4[CH:3]=3)=[CH:42][C:37]=2[O:36][CH2:35]1

Participants

8

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10796Cesium carbonateHCID 2734371(2H-1,3-benzodioxol-5-yl)boronic acidHCID 67258602Tert-butyl 4-[6-bromo-1-[(2-ethyl-2H-tetrazol-5-yl)methyl]-2,4-dioxo-1,4-dihydrothieno[3,2-d]pyrimidin-3(2H)-yl]piperidine-1-carboxylate

Product 1

HCID 67258894tert-butyl 4-[6-(1,3-benzodioxol-5-yl)-1-[(2-ethyl-2H-tetrazol-5-yl)methyl]-2,4-dioxo-1,4-dihydrothieno[3,2-d]pyrimidin-3(2H)-yl]piperidine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 11050900Dichlorobis(tricyclohexylphosphine)pallium (II)CatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Tert-butyl 4-{6-bromo-1-[(2-ethyl-2H-tetrazol-5-yl)methyl]-2,4-dioxo-1,4-dihydrothieno[3,2-d]pyrimidin-3(2H)-yl}piperidine-1-carboxylate (203 mg, B101), 1,3-benzodioxol-5-ylboronic acid (69 mg), dichlorobis(tricyclohexylphosphine)palladium (37 mg) and aqueous cesium carbonate solution (0.375 ml, 2.0 M) are placed in a microwave tube and DME (10 ml) is added. The reaction vessel is sealed and the mixture is subjected to microwave irradiation at 150° C. with stirring for 45 min. After addition of water and extraction with DCM the combined organic layers are washed with saturated aqueous sodium chloride solution and after filtration using a phase separator the organic layer is concentrated. The residue is purified by flash column chromatography [silica gel, elution gradient: cyclohexane/EtOAc, 100/0 to 50/50 to 30/70 (v/v)] to afford the title compound as a solid.

Workup

  1. customThe reaction vessel is sealed
  2. customirradiation at 150° C.
  3. washare washed with saturated aqueous sodium chloride solution
  4. filtrationafter filtration
  5. concentrationis concentrated
  6. customThe residue is purified by flash column chromatography [silica gel, elution gradient: cyclohexane/EtOAc, 100/0 to 50/50 to 30/70 (v/v)]

Sources & evidence

ORD record
ord-f273cc0c42a7421c9a226de9119df14c
Source dataset
uspto-grants-2015_04
Patent number
US09018175B2

Reaction notes

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