Imidazole → 4-[trans-3-(Tert-butyl-dimethyl-silanyloxy)-cyclopentylamino]-2-methylsulfanyl-pyrimidine-5-carbonitrile

HRID 2386682Notes

Reaction equation

HRID 2386682 reaction equation
[OH:1][C@H:2]1[CH2:6][CH2:5][C@H:4]([NH:7][C:8]2[C:13]([C:14]#[N:15])=[CH:12][N:11]=[C:10]([S:16][CH3:17])[N:9]=2)[CH2:3]1.N1C=CN=C1.[Si:23](Cl)([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24]>CN(C=O)C>[C:26]([Si:23]([CH3:25])([CH3:24])[O:1][C@H:2]1[CH2:6][CH2:5][C@H:4]([NH:7][C:8]2[C:13]([C:14]#[N:15])=[CH:12][N:11]=[C:10]([S:16][CH3:17])[N:9]=2)[CH2:3]1)([CH3:29])([CH3:28])[CH3:27]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 66955848trans-4-(3-Hydroxy-cyclopentylamino)-2-methylsulfanyl-pyrimidine-5-carbonitrile

Product 1

HCID 669551674-[trans-3-(Tert-butyl-dimethyl-silanyloxy)-cyclopentylamino]-2-methylsulfanyl-pyrimidine-5-carbonitrileYield 90.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of trans-4-(3-hydroxy-cyclopentylamino)-2-methylsulfanyl-pyrimidine-5-carbonitrile (500 mg, 2.0 mmol) in anhydrous DMF (15 mL) was added, at RT, under argon atmosphere, imidazole (680 mg, 10.0 mmol) followed by tert-butyldimethylsilylchloride (750 mg, 5.0 mmol) and the resulting mixture was stirred at RT for 64 h. The reaction mixture was quenched with NH4Cl (sat'd aq, 20 mL) and was 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 purified by flash chromatography (hexane/EtOAc, 95/5) to give 660 mg of 4-[trans-3-(tert-butyl-dimethyl-silanyloxy)-cyclopentylamino]-2-methylsulfanyl-pyrimidine-5-carbonitrile as a white solid.

Workup

  1. additionwas added, at RT, under argon atmosphere
  2. customThe reaction mixture was quenched with NH4Cl (sat'd aq, 20 mL)
  3. extractionwas extracted 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. customThe crude residue was purified by flash chromatography (hexane/EtOAc, 95/5)

Sources & evidence

ORD record
ord-543e3345f27d494091b42f600557612c
Source dataset
uspto-grants-2012_09
Patent number
US08268840B2

Reaction notes

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