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

HRID 588191Notes

Reaction equation

HRID 588191 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH2:8][O:9][CH3:10])[C:5]2[C:11]([O:33][CH3:34])=[N:12][N:13](C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[C:4]=2[CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[C:41]1([C@H:47]([NH:49][C:50]([NH2:52])=[O:51])[CH3:48])[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1>CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=C(OC)C=CC=2OC)=C(C(C)C)C=1)C.O1CCOCC1.C(Cl)Cl>[CH3:34][O:33][C:11]1[C:5]2[C:6]([CH2:8][O:9][CH3:10])=[N:7][C:2]([NH:52][C:50]([NH:49][C@@H:47]([C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[CH3:48])=[O:51])=[CH:3][C:4]=2[NH:13][N:12]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 13013340(R)-1-(1-phenylethyl)ureaHCID 1182718036-chloro-3-methoxy-4-(methoxymethyl)-1-trityl-1H-pyrazolo[4,3-c]pyridine

Product 1

HCID 118272293(R)-1-(3-methoxy-4-(methoxymethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea

Reagents, catalysts & solvents 3

HCID 25112535BrettphosCatalystHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

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).

Workup

  1. customthe vial was evacuated
  2. additionback-filled with N2 (×3)
  3. customThe crude reaction mixture
  4. filtrationfiltered through a syringe
  5. filtrationfilter
  6. concentrationthe filtrate was concentrated in vacuo
  7. dissolutionThe residue was dissolved in TFA (2 mL)
  8. additioncharged with triethylsilane (100 uL)
  9. stirringstirred at room temperature for 10 min
  10. concentrationThe reaction mixture was concentrated in vacuo
  11. customthe residue was purified by mass-triggered reverse phase HPLC
  12. additionFractions containing pure compound
  13. filtrationwere filtered through a PS—HCO3 cartridge
  14. concentrationthe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-f78a8450df1b44138a17f2af7eef27d4
Source dataset
uspto-grants-2016_01
Patent number
US09226922B2

Reaction notes

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