반응 #166351

반응 방정식

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

수율 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

수율 50.0%

용매

methanol

methanol

THF

THF

반응 조건

후처리

1. 1
   기타The solvent was evaporated
2. 2
   기타to give an orange oil
3. 3
   세척Preparative reverse phase HPLC (gradient elution 0.1% TFA in water/10-70% acetonitrile)
4. 4
   기타afforded a yellow solid
5. 5
   추출extracted with dichloromethane+10% methanol (3×30 mL)
6. 6
   건조The combined organics were dried (MgSO4)
7. 7
   기타evaporated
8. 8
   기타to give a yellow solid
9. 9
   기타to precipitate the product, which
10. 10
    세척was washed with ether
11. 11
    기타dried in vacuo

실험 절차

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.

출처