Réaction #166351

Équation de réaction

diethyl ether

Tetrabutylammonium fluoride

Compound 276

9-Cyclopentyl-2-((5-((3R)-3-(tert-butyldimethylsilyloxy)pyrrolidin-1-yl)-2-pyridinyl)amino)-8-methyl-8,9-dihydro-7H-pyrido[3′,2′:4,5]pyrrolo[2,3-d]-pyrimidin-7-one

NaHCO3

→

compound 275

Rendement 50.0%

9-Cyclopentyl-2-((5-((3R)-3-hydroxy-1-pyrrolidinyl)-2-pyridinyl)amino)-8-methyl-8,9-dihydro-7H-pyrido[3′,2′:4,5]pyrrolo[2,3-d]pyrimidin-7-one

Rendement 50.0%

Solvants

methanol

methanol

THF

THF

Conditions de réaction

Traitement

1. 1
   AutreThe solvent was evaporated
2. 2
   Autreto give an orange oil
3. 3
   LavagePreparative reverse phase HPLC (gradient elution 0.1% TFA in water/10-70% acetonitrile)
4. 4
   Autreafforded a yellow solid
5. 5
   Extractionextracted with dichloromethane+10% methanol (3×30 mL)
6. 6
   SéchageThe combined organics were dried (MgSO4)
7. 7
   Autreevaporated
8. 8
   Autreto give a yellow solid
9. 9
   Autreto precipitate the product, which
10. 10
    Lavagewas washed with ether
11. 11
    Autredried in vacuo

Mode opératoire

Compound 276 (53.0 mg, 94.7 μmol) was dissolved in THF (2 mL).). Tetrabutylammonium fluoride, 1.0M in THF (0.500 mL, 500 μmol) was added and the reaction was stirred at room temperature for 4.5 hours. The solvent was evaporated to give an orange oil. Preparative reverse phase HPLC (gradient elution 0.1% TFA in water/10-70% acetonitrile) afforded a yellow solid. This residue was added to aqueous NaHCO3 (saturated, 10 mL) and extracted with dichloromethane+10% methanol (3×30 mL). The combined organics were dried (MgSO4) and evaporated to give a yellow solid. This product was taken up in methanol (2 mL) and 1 mL methanol (saturated at room temperature with HCl) was added. 20 mL diethyl ether was added to precipitate the product, which was washed with ether and dried in vacuo to give compound 275 as yellow solid (21 mg, 50%). 1H NMR (500 MHz, DMSO-d6) δ 9.21 (s, 2 H) 8.56 (d, J=8.56 Hz, 2 H) 7.63 (d, J=2.69 Hz, 4 H) 7.44-7.57 (m, 2 H) 6.87 (d, J=8.56 Hz, 2 H) 5.43 (quin, J=8.62 Hz, 1 H) 4.47 (br. s., 1 H) 4.00 (s, 3 H) 3.09-3.21 (m, 1H) 2.00-2.22 (m, 5 H) 1.90-2.04 (m, 1 H) 1.66-1.85 (m, 2 H) ppm.

Source