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

HRID 588188Notes

Reaction equation

HRID 588188 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH3:8])[C:5]2[C:9](=[O:31])[NH:10][N:11]([C:12]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:4]=2[CH:3]=1.[C:32]1([C@H:38]([NH:40][C:41]([NH2:43])=[O:42])[CH3:39])[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:8][C:6]1[C:5]2[C:9](=[O:31])[NH:10][N:11]([C:12]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)([C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)[C:4]=2[CH:3]=[C:2]([NH:43][C:41]([NH:40][C@@H:38]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH3:39])=[O:42])[N:7]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 13013340(R)-1-(1-phenylethyl)ureaHCID 1182721366-chloro-4-methyl-1-trityl-1H-pyrazolo[4,3-c]pyridin-3(2H)-one2×

Product 1

HCID 118272012(R)-1-(4-methyl-3-oxo-1-trityl-2,3-dihydro-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

6-Chloro-4-methyl-1-trityl-1H-pyrazolo[4,3-c]pyridin-3 (2H)-one (Intermediate 4B; 300 mg, 0.704 mmol), (R)-1-(1-phenylethyl)urea (139 mg, 0.845 mmol), palladium(II) acetate (31.6 mg, 0.141 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (122 mg, 0.211 mmol), and cesium carbonate (574 mg, 1.761 mmol) were taken up in dioxane (10.0 mL) in a 25 mL microwave vial. The vial was evacuated and back-filled with N2 (×3) then the reaction mixture was heated to 80° C. for 24 h. The reaction mixture was diluted with DCM, filtered through celite, and the filtrate was washed with water then brine. The organic layer was dried over sodium sulfate, filtered, concentrated in vacuo, and purified by flash chromatography (20-80% EtOAc/Hexanes) to give (R)-1-(4-methyl-3-oxo-1-trityl-2,3-dihydro-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea. MS ESI calc'd. For C35H31N5O2 [M+1]+ 554. found 554.

Workup

  1. customThe vial was evacuated
  2. additionback-filled with N2 (×3)
  3. additionThe reaction mixture was diluted with DCM
  4. filtrationfiltered through celite
  5. washthe filtrate was washed with water
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. custompurified by flash chromatography (20-80% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-addc161ea0394e22b3b2f793125db281
Source dataset
uspto-grants-2016_01
Patent number
US09226922B2

Reaction notes

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