Sodium Iodide → 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

HRID 1476661Notes

Reaction equation

HRID 1476661 reaction equation
[Br:1][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.Cl[CH2:27][C:28]1[N:29]=[N:30][N:31]([CH2:33][CH3:34])[N:32]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[I-].[Na+]>C1COCC1>[Br:1][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]([CH3:22])([CH3:24])[CH3:23])=[O:19])[CH2:14][CH2:13]3)[C:6](=[O:25])[N:5]([CH2:27][C:28]3[N:29]=[N:30][N:31]([CH2:33][CH3:34])[N:32]=3)[C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 122050825-(chloromethyl)-2-ethyl-2H-tetrazoleHCID 67258027HCID 67258027, compound

Product 1

HCID 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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
45 °C

Procedure

To a solution of tert-butyl 4-(6-bromo-2,4-dioxo-1,4-dihydrothieno[3,2-d]pyrimidin-3(2H)-yl)piperidine-1-carboxylate (5.00 g, compound B53) in anhydrous THF (100 ml) is slowly added 5-(chloromethyl)-2-ethyl-2H-tetrazole (5.62 g, compound D32), sodium bis(trimethylsilyl)amide (11.6 ml, 1.0 M solution in THF) and sodium iodide (348 mg). The reaction mixture is stirred for 48 h at 45° C. Afterwards all volatiles are removed under reduced pressure and the residue is treated with DCM (100 ml) and water (50 ml). The organic layer is separated and dried over sodium sulfate. After purification by flash column chromatography [silica gel, eluation gradient: EtOAc/cyclohexane, 1/1 (v/v)] the title compound is obtained as a solid.

Workup

  1. customAfterwards all volatiles are removed under reduced pressure
  2. additionthe residue is treated with DCM (100 ml) and water (50 ml)
  3. customThe organic layer is separated
  4. dry with materialdried over sodium sulfate
  5. customAfter purification by flash column chromatography [silica gel, eluation gradient: EtOAc/cyclohexane, 1/1 (v/v)] the title compound
  6. customis obtained as a solid

Sources & evidence

ORD record
ord-3ce31ec340154425a485986f19986f81
Source dataset
uspto-grants-2015_04
Patent number
US09018175B2

Reaction notes

Loading…