Piperazine → HCID 46916887, compound

HRID 718263Notes

Reaction equation

HRID 718263 reaction equation
[NH2:1][C:2]1[N:3]=[C:4](SC)[C:5]2[N:10]=[C:9]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=3)[S:8][C:6]=2[N:7]=1.[OH-].[Na+].[CH:23]1(I)[CH2:27][CH2:26][CH2:25][CH2:24]1.ClC1C=C(C=CC=1)C(OO)=O.[NH:40]1[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]1.[Cl:46][C:47]1[CH:57]=[CH:56][C:50]([O:51][CH2:52][C:53](Cl)=[O:54])=[CH:49][CH:48]=1.C(N(C(C)C)CC)(C)C>CS(C)=O>[NH2:1][C:2]1[N:3]=[C:4]([N:40]2[CH2:45][CH2:44][N:43]([C:53](=[O:54])[CH2:52][O:51][C:50]3[CH:56]=[CH:57][C:47]([Cl:46])=[CH:48][CH:49]=3)[CH2:42][CH2:41]2)[C:5]2[N:10]=[C:9]([CH:11]([CH:23]3[CH2:27][CH2:26][CH2:25][CH2:24]3)[C:12]3[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=3)[S:8][C:6]=2[N:7]=1

Participants

9

Reactant 7

HCID 4837PiperazineHCID 14798Sodium HydroxideHCID 70297m-Chloroperbenzoic acidHCID 73784IodocyclopentaneHCID 77771p-Chlorophenoxyacetyl chlorideHCID 81531DiisopropylethylamineHCID 50941767HCID 50941767, compound

Product 1

HCID 46916887HCID 46916887, compoundYield 24.5%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of 5-amino-2-(4-fluorobenzyl)-7-methylsulfanylthiazolo[5,4-d]pyrimidine (100 mg, 0.33 mmol) in DMSO (1.5 ml) was added sodium hydroxide (2N, 171 μL) and cyclopentyl iodide (0.34 mmol). The reaction mixture was stirred at room temperature for 16 hours whereupon the mixture was extracted with ethyl acetate and brine. The organic phase was dried over magnesium sulfate and concentrated by evaporation in vacuo. The resulting residue was dissolved in dichloromethane (3 ml), cooled to 0° C. and m-chloroperoxybenzoic acid (0.81 mmol) was added. The reaction mixture was stirred at room temperature for 7 hours. The mixture was first extracted with a saturated sodium bicarbonate solution, then with brine. The combined organic phases were dried over magnesium sulfate. After evaporating the solvents in vacuo, the residue was redissolved in dichloromethane (3 ml) and piperazine (3.3 mmol) was added. The reaction mixture was stirred at room temperature for 16 hours whereupon the mixture was extracted with brine. The organic phase was dried over magnesium sulfate and evaporated in vacuo. The crude residue was reacted at room temperature for 16 hours with 4-chlorophenoxyacetyl chloride (0.35 mmol) in the presence of diisopropylethylamine (0.72 mmol, 119 μL). After removing the solvent in vacuo, the crude mixture was purified by flash chromatography on silica, the mobile phase being a mixture of methanol and dichloromethane (in a ratio gradually ranging from 100% CH2Cl2 to 1.5% CH3OH in CH2Cl2), yielding the pure title compound (47 mg) which was characterized by its mass spectrum: MS m/z (%): 581 ([M+H]+, 100).

Workup

  1. extractionwas extracted with ethyl acetate and brine
  2. dry with materialThe organic phase was dried over magnesium sulfate
  3. concentrationconcentrated by evaporation in vacuo
  4. dissolutionThe resulting residue was dissolved in dichloromethane (3 ml)
  5. temperaturecooled to 0° C.
  6. stirringThe reaction mixture was stirred at room temperature for 7 hours
  7. extractionThe mixture was first extracted with a saturated sodium bicarbonate solution
  8. dry with materialThe combined organic phases were dried over magnesium sulfate
  9. customAfter evaporating the solvents in vacuo
  10. dissolutionthe residue was redissolved in dichloromethane (3 ml)
  11. stirringThe reaction mixture was stirred at room temperature for 16 hours whereupon the mixture
  12. extractionwas extracted with brine
  13. dry with materialThe organic phase was dried over magnesium sulfate
  14. customevaporated in vacuo
  15. customAfter removing the solvent in vacuo
  16. customthe crude mixture was purified by flash chromatography on silica
  17. additiona mixture of methanol and dichloromethane (in a ratio

Sources & evidence

ORD record
ord-2c821660da9a44c79b0791dd6e964051
Source dataset
uspto-grants-2015_11
Patent number
US09193741B2

Reaction notes

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