反応 #166351

反応方程式

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

収率 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

収率 50.0%

溶媒

methanol

methanol

THF

THF

反応条件

後処理

1. 1
   その他The solvent was evaporated
2. 2
   その他to give an orange oil
3. 3
   洗浄Preparative reverse phase HPLC (gradient elution 0.1% TFA in water/10-70% acetonitrile)
4. 4
   その他afforded a yellow solid
5. 5
   抽出extracted with dichloromethane+10% methanol (3×30 mL)
6. 6
   乾燥The combined organics were dried (MgSO4)
7. 7
   その他evaporated
8. 8
   その他to give a yellow solid
9. 9
   その他to precipitate the product, which
10. 10
    洗浄was washed with ether
11. 11
    その他dried in vacuo

実験手順

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.

出典