Carbon tetrabromide → tert-butyl 4-{1-[(5-ethyl-2H-tetrazol-2-yl)methyl]-2,4-dioxo-6-phenyl-1,4-dihydrothieno[3,2-d]pyrimidin-3(2H)-yl}piperidine-1-carboxylate

HRID 1476637Notes

Reaction equation

HRID 1476637 reaction equation
[CH2:1]([C:3]1[N:4]=[N:5][N:6]([CH2:8]O[Si](C(C)C)(C(C)C)C(C)C)[N:7]=1)[CH3:2].[N+](CCCC)(CCCC)(CCCC)CCCC.[F-].C(Br)(Br)(Br)Br.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[O:62]=[C:63]1[NH:68][C:67]2[CH:69]=[C:70]([C:72]3[CH:77]=[CH:76][CH:75]=[CH:74][CH:73]=3)[S:71][C:66]=2[C:65](=[O:78])[N:64]1[CH:79]1[CH2:84][CH2:83][N:82]([C:85]([O:87][C:88]([CH3:91])([CH3:90])[CH3:89])=[O:86])[CH2:81][CH2:80]1.C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl.CN(C=O)C>[CH2:1]([C:3]1[N:4]=[N:5][N:6]([CH2:8][N:68]2[C:67]3[CH:69]=[C:70]([C:72]4[CH:77]=[CH:76][CH:75]=[CH:74][CH:73]=4)[S:71][C:66]=3[C:65](=[O:78])[N:64]([CH:79]3[CH2:84][CH2:83][N:82]([C:85]([O:87][C:88]([CH3:90])([CH3:89])[CH3:91])=[O:86])[CH2:81][CH2:80]3)[C:63]2=[O:62])[N:7]=1)[CH3:2]

Participants

9

Reactant 6

HCID 11205Carbon tetrabromideHCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 2724141Tetrabutylammonium FluorideHCID 67257815tert-butyl 4-(2,4-dioxo-6-phenyl-1,4-dihydrothieno[3,2-d]pyrimidin-3(2H)-yl)piperidine-1-carboxylateHCID 672584275-ethyl-2-{[(tripropan-2-ylsilyl)oxy]methyl}-2H-tetrazole2×

Product 1

HCID 67257980tert-butyl 4-{1-[(5-ethyl-2H-tetrazol-2-yl)methyl]-2,4-dioxo-6-phenyl-1,4-dihydrothieno[3,2-d]pyrimidin-3(2H)-yl}piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-ethyl-2-{[(tripropan-2-ylsilyl)oxy]methyl}-2H-tetrazole (1.53 g; compound D30) in DCM is added n-Bu4NF (5.34 ml of 1M solution in THF) and stirred for 30 min at RT. After completion of the reaction (TLC monitoring, eluent system: EtOAc/c-Hexan, 1/6, (v/v)) CBr4 (2.13 g) and PPh3 (1.68 g) are added and the reaction mixture is stirred for 30 min at RT. The reaction mixture is added to a mixture of tert-butyl 4-(2,4-dioxo-6-phenyl-1,4-dihydrothieno[3,2-d]pyrimidin-3(2H)-yl)piperidine-1-carboxylate (913 mg; compound B50) and potassium carbonate (1.33 g) in DMF and the combined reaction mixture is stirred for 12 h at 80° C. All volatiles are evaporated under reduced pressure and the resulting residue is purified by flash chromatography (silica gel, eluent EtOAc/cyclohexane, 1/6, (v/v)) to give the title compound as a solid.

Workup

  1. additionare added
  2. stirringthe reaction mixture is stirred for 30 min at RT
  3. customthe combined reaction mixture
  4. stirringis stirred for 12 h at 80° C
  5. customAll volatiles are evaporated under reduced pressure
  6. customthe resulting residue is purified by flash chromatography (silica gel, eluent EtOAc/cyclohexane, 1/6, (v/v))

Sources & evidence

ORD record
ord-c912f5082f69447dbd7cb8331c3c2735
Source dataset
uspto-grants-2015_04
Patent number
US09018175B2

Reaction notes

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