Acetic Anhydride → 5-amino-8-[trans-3-(tert-butyl-dimethyl-silanyloxy)-cyclopentyl]-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-one

HRID 2386683Notes

Reaction equation

HRID 2386683 reaction equation
[H-].[Na+].[C:3]([Si:7]([CH3:26])([CH3:25])[O:8][C@H:9]1[CH2:13][CH2:12][C@H:11]([NH:14][C:15]2[C:20]([C:21]#[N:22])=[CH:19][N:18]=[C:17]([S:23][CH3:24])[N:16]=2)[CH2:10]1)([CH3:6])([CH3:5])[CH3:4].[CH3:27][C:28](OC(C)=O)=[O:29].O.NN>CN(C=O)C>[NH2:22][C:21]1[C:20]2[CH:19]=[N:18][C:17]([S:23][CH3:24])=[N:16][C:15]=2[N:14]([C@H:11]2[CH2:12][CH2:13][C@H:9]([O:8][Si:7]([C:3]([CH3:6])([CH3:5])[CH3:4])([CH3:26])[CH3:25])[CH2:10]2)[C:28](=[O:29])[CH:27]=1

Participants

6

Reactant 4

HCID 7918Acetic AnhydrideHCID 24654Hydrazine hydrate (1:1)HCID 24758Sodium hydrideHCID 669551674-[trans-3-(Tert-butyl-dimethyl-silanyloxy)-cyclopentylamino]-2-methylsulfanyl-pyrimidine-5-carbonitrile

Product 1

HCID 669555755-amino-8-[trans-3-(tert-butyl-dimethyl-silanyloxy)-cyclopentyl]-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-oneYield 108.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (60% suspension in mineral oil, 303 mg, 7.59 mmol) was added in one portion, under argon atmosphere, to a mixture of 4-[trans-3-(tert-butyl-dimethyl-silanyloxy)-cyclopentylamino]-2-methylsulfanyl-pyrimidine-5-carbonitrile (658 mg, 1.81 mmol) in anhydrous DMF (10 mL) and the resulting mixture was stirred at RT for 30 min. Anhydrous Ac2O (2.56 mL, 27.1 mmol) was added dropwise, over a period of 35 min, and the reaction mixture was stirred for additional 10 min. The resulting mixture was quenched with NH4Cl (sat'd aq, 50 mL), and extracted with EtOAc (3×20 mL). The combined organic layers were washed with water (2×10 mL), dried over Na2SO4, filtered and evaporated under reduced pressure. The crude residue was dissolved in MeOH (15 mL), and hydrazine hydrate (0.877 mL, 18.08 mmol) was added dropwise. The resulting mixture was heated at 85° C. in a microwave reactor for 50 min. The solvent was evaporated under reduced pressure and water was added to the residue. The resulting mixture was extracted with EtOAc (3×20 mL). The combined organic layers were washed with water (3×10 mL), dried over Na2SO4, filtered and evaporated under reduced pressure. The crude residue was purified by flash chromatography (DCM/MeOH) to afford 800 mg of 5-amino-8-[trans-3-(tert-butyl-dimethyl-silanyloxy)-cyclopentyl]-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-one.

Workup

  1. stirringthe reaction mixture was stirred for additional 10 min
  2. customThe resulting mixture was quenched with NH4Cl (sat'd aq, 50 mL)
  3. extractionextracted with EtOAc (3×20 mL)
  4. washThe combined organic layers were washed with water (2×10 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customevaporated under reduced pressure
  8. dissolutionThe crude residue was dissolved in MeOH (15 mL)
  9. temperatureThe resulting mixture was heated at 85° C. in a microwave reactor for 50 min
  10. customThe solvent was evaporated under reduced pressure and water
  11. additionwas added to the residue
  12. extractionThe resulting mixture was extracted with EtOAc (3×20 mL)
  13. washThe combined organic layers were washed with water (3×10 mL)
  14. dry with materialdried over Na2SO4
  15. filtrationfiltered
  16. customevaporated under reduced pressure
  17. customThe crude residue was purified by flash chromatography (DCM/MeOH)

Sources & evidence

ORD record
ord-c571ddc63f6c40b48ce491204ab6ea25
Source dataset
uspto-grants-2012_09
Patent number
US08268840B2

Reaction notes

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