Phosphorus sulfide (P2S5) → 3-[4-(2-Oxo-3-propyl-6-thioxo-2,3,6,7-tetrahydro-1H-purin-8-yl)-bicyclo[2.2.2]oct-1-yl]-propionic acid methyl ester

HRID 395284Notes

Reaction equation

HRID 395284 reaction equation
[CH3:1][O:2][C:3](=[O:28])[CH2:4][CH2:5][C:6]12[CH2:13][CH2:12][C:9]([C:14]3[NH:22][C:21]4[C:20](=O)[NH:19][C:18](=[O:24])[N:17]([CH2:25][CH2:26][CH3:27])[C:16]=4[N:15]=3)([CH2:10][CH2:11]1)[CH2:8][CH2:7]2.P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:30]>N1C=CC=CC=1>[CH3:1][O:2][C:3](=[O:28])[CH2:4][CH2:5][C:6]12[CH2:13][CH2:12][C:9]([C:14]3[NH:22][C:21]4[C:20](=[S:30])[NH:19][C:18](=[O:24])[N:17]([CH2:25][CH2:26][CH3:27])[C:16]=4[N:15]=3)([CH2:10][CH2:11]1)[CH2:8][CH2:7]2

Participants

4

Reactant 2

HCID 14817Phosphorus sulfide (P2S5)HCID 213520793-[4-(2,6-Dioxo-3-propyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-bicyclo[2.2.2]oct-1-yl]-propionic acid methyl ester

Product 1

HCID 865856363-[4-(2-Oxo-3-propyl-6-thioxo-2,3,6,7-tetrahydro-1H-purin-8-yl)-bicyclo[2.2.2]oct-1-yl]-propionic acid methyl esterYield 38.6%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

3-[4-(2,6-Dioxo-3-propyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-bicyclo[2.2.2]oct-1-yl]-propionic acid methyl ester (250 mg, 0.64 mmol) was dissolved in 8 mL of pyridine. P4S10 (430 mg, 1.5 eq) was added and the reaction mixture was stirred under reflux for 3 h. It was then cooled to rt and quenched with 3 mL of H2O and then with enough 6 N HCl to bring the pH to 3. The resulting reaction mixture was extracted with CHCl3. The organic layer was dried (Na2SO4) and concentrated under reduced pressure. The crude residue was purified by preparative HPLC to afford 100 mg of the desired product.

Workup

  1. temperatureunder reflux for 3 h
  2. customquenched with 3 mL of H2O
  3. customThe resulting reaction mixture
  4. extractionwas extracted with CHCl3
  5. dry with materialThe organic layer was dried (Na2SO4)
  6. concentrationconcentrated under reduced pressure
  7. customThe crude residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-b9a4a6f35a8943baa89ebf1fa64298de
Source dataset
uspto-grants-2003_08
Patent number
US06605601B2

Reaction notes

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