Reaktion #675373

Reaktionsgleichung

6-chloro-3-methoxy-4-(methoxymethyl)-1-trityl-1H-pyrazolo[4,3-c]pyridine

cesium carbonate

(R)-1-(1-phenylethyl)urea

→

(R)-1-(3-methoxy-4-(methoxymethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea

Lösungsmittel

DCM

dioxane

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigethe vial was evacuated
2. 2
   workup.ADDITIONback-filled with N2 (×3)
3. 3
   SonstigeThe crude reaction mixture
4. 4
   Filtrationfiltered through a syringe
5. 5
   Filtrationfilter
6. 6
   Einengenthe filtrate was concentrated in vacuo
7. 7
   workup.DISSOLUTIONThe residue was dissolved in TFA (2 mL)
8. 8
   workup.ADDITIONcharged with triethylsilane (100 uL)
9. 9
   workup.STIRRINGstirred at room temperature for 10 min
10. 10
    EinengenThe reaction mixture was concentrated in vacuo
11. 11
    Sonstigethe residue was purified by mass-triggered reverse phase HPLC
12. 12
    workup.ADDITIONFractions containing pure compound
13. 13
    Filtrationwere filtered through a PS—HCO3 cartridge
14. 14
    Einengenthe filtrate was concentrated in vacuo

Vorschrift

BrettPhos pre-catalyst (6.80 mg, 8.51 μmol), 6-chloro-3-methoxy-4-(methoxymethyl)-1-trityl-1H-pyrazolo[4,3-c]pyridine (40 mg, 0.085 mmol), cesium carbonate (83 mg, 0.255 mmol), and (R)-1-(1-phenylethyl)urea (20.96 mg, 0.128 mmol) were taken up in dioxane (1 mL) in a 1.5 mL microwave vial and the vial was evacuated and back-filled with N2 (×3). The reaction mixture was stirred at 90° C. for 2 h. The crude reaction mixture was diluted with DCM, filtered through a syringe filter, and the filtrate was concentrated in vacuo. The residue was dissolved in TFA (2 mL), charged with triethylsilane (100 uL), and stirred at room temperature for 10 min. The reaction mixture was concentrated in vacuo and the residue was 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-(3-methoxy-4-(methoxymethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea. MS ESI calc'd. For C18H21N5O3 [M+1]+ 356. found 356. 1H NMR (500 MHz, CD3OD) δ 7.42-7.32 (m, 4H), 7.25 (m, 4H), 6.86 (s, 1H), 5.02 (br s, 2H), 5.01-4.98 (m, 1H), 4.10 (s, 3H), 3.58 (s, 3H), 1.53 (d, J=7.0 Hz, 3H).

Quelle