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

HRID 588189Notes

Reaction equation

HRID 588189 reaction equation
[CH3:1][C:2]1[C:7]2[C:8](=[O:30])[NH:9][N:10](C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[C:6]=2[CH:5]=[C:4]([NH:31][C:32]([NH:34][C@@H:35]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[CH3:36])=[O:33])[N:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].I[CH:50]1[CH2:55][CH2:54][O:53][CH2:52][CH2:51]1.C([SiH](CC)CC)C>CN(C=O)C.CS(C)=O>[CH3:1][C:2]1[C:7]2[C:8]([O:30][CH:50]3[CH2:55][CH2:54][O:53][CH2:52][CH2:51]3)=[N:9][NH:10][C:6]=2[CH:5]=[C:4]([NH:31][C:32]([NH:34][C@@H:35]([C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=2)[CH3:36])=[O:33])[N:3]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 12052TriethylsilaneHCID 27955064-iodotetrahydro-2H-pyranHCID 118272012(R)-1-(4-methyl-3-oxo-1-trityl-2,3-dihydro-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea

Product 1

HCID 118272067(R)-1-(4-methyl-3-((tetrahydro-2H-pyran-4-yl)oxy)-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6228DimethylformamideSolvent

Procedure

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).

Workup

  1. customThe reaction was quenched with MeOH
  2. concentrationconcentrated in vacuo
  3. dissolutionThe residue was dissolved in TFA (2 mL)
  4. stirringstirred at room temperature for 2 h
  5. custompurified by mass-triggered reverse-phase HPLC
  6. additionFractions containing pure compound
  7. filtrationwere filtered through a PS—HCO3 cartridge
  8. concentrationthe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-2a3027144e3543709945afef49bbad63
Source dataset
uspto-grants-2016_01
Patent number
US09226922B2

Reaction notes

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