反応 #675371

反応方程式

triethylsilane

(R)-1-(4-methyl-3-oxo-1-trityl-2,3-dihydro-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea

Cs2CO3

4-iodotetrahydro-2H-pyran

→

(R)-1-(4-methyl-3-((tetrahydro-2H-pyran-4-yl)oxy)-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea

溶媒

DMSO

DMF

反応条件

後処理

1. 1
   その他The reaction was quenched with MeOH
2. 2
   濃縮concentrated in vacuo
3. 3
   workup.DISSOLUTIONThe residue was dissolved in TFA (2 mL)
4. 4
   workup.STIRRINGstirred at room temperature for 2 h
5. 5
   その他purified by mass-triggered reverse-phase HPLC
6. 6
   workup.ADDITIONFractions containing pure compound
7. 7
   ろ過were filtered through a PS—HCO3 cartridge
8. 8
   濃縮the filtrate was concentrated in vacuo

実験手順

A mixture of (R)-1-(4-methyl-3-oxo-1-trityl-2,3-dihydro-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea (50 mg, 0.090 mmol), Cs2CO3 (91 mg, 0.279 mmol), and 4-iodotetrahydro-2H-pyran (25 μL, 0.209 mmol) in DMF (1 mL) was stirred at room temperature for 18 h. The reaction was quenched with MeOH and concentrated in vacuo. The residue was dissolved in TFA (2 mL), charged with triethylsilane (0.02 mL, 0.125 mmol), and stirred at room temperature for 2 h. The reaction mixture was diluted with DMSO (4 mL) and purified by mass-triggered reverse-phase HPLC. Fractions containing pure compound were filtered through a PS—HCO3 cartridge and the filtrate was concentrated in vacuo to give (R)-1-(4-methyl-3-((tetrahydro-2H-pyran-4-yl)oxy)-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea. MS ESI calc'd. For C21H25N5O3 [M+1]+ 396. found 396. 1H NMR (500 MHz, DMSO-d6) δ 8.96 (s, 1H), 8.12 (br s, 1H), 7.33 (m, 4H), 7.22 (m, 1H), 7.16 (br s, 1H), 4.95 (m, 1H), 4.84 (quintuplet, J=7.1 Hz, 1H), 3.84 (m, 2H), 3.52 (m, 2H), 2.59 (s, 3H), 2.06 (m, 1H), 1.71 (m, 1H), 1.39 (d, J=7.1 Hz, 3H).

出典