p-Toluenesulfonic acid → HCID 178478373, compound

HRID 334119Notes

Reaction equation

HRID 334119 reaction equation
[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([I:17])[N:8]2C2CCCCO2)=[C:4]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)[N:3]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([I:17])[NH:8]2)=[C:4]([N:18]2[CH2:19][CH2:20][O:21][CH2:22][CH2:23]2)[N:3]=1

Participants

4

Reactant 2

HCID 6101p-Toluenesulfonic acidHCID 596052352-Chloro-8-iodo-6-morpholin-4-yl-9-(tetrahydropyran-2-yl)-9H-purine

Product 1

HCID 178478373HCID 178478373, compoundYield 56%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

To a suspension of 4-(2-chloro-8-iodo-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)morpholine (0.655 g, 1.46 mmol) in methanol (6 mL) was added a catalytic amount of p-toluenesulfonic acid (25 mg, 0.14 mmol). The reaction mixture was heated at 50° C. for an overnight period. After this time, the mixture was cooled to room temperature and the volume of methanol was reduced by vacuum evaporation. The resulting residue was diluted with sat. aqueous NaHCO3 solution. The precipitate that formed was collected by filtration. In total, 295 mg (56%) of 4-(2-chloro-8-iodo-9H-purin-6-yl)morpholine was obtained as a white solid which was dissolved in anhydrous DMF (2.5 mL). Cesium carbonate (0.53 g, 1.61 mmol) was added and the mixture was stirred together 10 min at 23° C. Subsequently 1-(2H-3,4,5,6-tetrahydropyran-2-yloxy)-3-bromopropane (0.54 g, 2.42 mmol) was introduced to the mixture. The resulting reaction mixture was heated at 50° C. for 2 h. Complete conversion was observed at the end of this period. The reaction was worked up by dilution with 1 N HCl and EtOAc. The phases were separated and the aqueous layer was extracted twice with EtOAc. The combined organic portions were dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by FCC (40 g silica gel column, 0-50% EtOAc in heptane) to give 385 mg (94% yield) of 4-(2-chloro-8-iodo-9-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-9H-purin-6-yl)morpholine as a pale yellow solid. MS (ESI+): m/z 508.0 (M+H+)

Workup

  1. temperatureAfter this time, the mixture was cooled to room temperature
  2. customthe volume of methanol was reduced by vacuum evaporation
  3. additionThe resulting residue was diluted with sat. aqueous NaHCO3 solution
  4. customThe precipitate that formed
  5. filtrationwas collected by filtration

Sources & evidence

ORD record
ord-b738399aaf4149758f1b0464002e62d3
Source dataset
uspto-grants-2014_11
Patent number
US08883799B2

Reaction notes

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