Cesium carbonate → 1-(3-cyclopropyl-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(4-fluorobenzyl)urea

HRID 571404Notes

Reaction equation

HRID 571404 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]2[C:8]([CH:30]3[CH2:32][CH2:31]3)=[N:9][N:10]([C:11]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:4]=2[CH:3]=1.[F:33][C:34]1[CH:44]=[CH:43][C:37]([CH2:38][NH:39][C:40]([NH2:42])=[O:41])=[CH:36][CH:35]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:30]1([C:8]2[C:5]3[CH:6]=[N:7][C:2]([NH:42][C:40]([NH:39][CH2:38][C:37]4[CH:43]=[CH:44][C:34]([F:33])=[CH:35][CH:36]=4)=[O:41])=[CH:3][C:4]=3[N:10]([C:11]([C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)([C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)[C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)[N:9]=2)[CH2:31][CH2:32]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 27372894-FluorobenzylureaHCID 1176008606-chloro-3-cyclopropyl-1-trityl-1H-pyrazolo[4,3-c]pyridine

Product 1

HCID 895259191-(3-cyclopropyl-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(4-fluorobenzyl)ureaYield 90%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
80 °C

Procedure

A mixture of 6-chloro-3-cyclopropyl-1-trityl-1H-pyrazolo[4,3-c]pyridine (60 mg, 0.138 mmol), 1-(4-fluorobenzyl)urea (69 mg, 0.413 mmol), palladium(II) acetate (6 mg, 0.028 mmol), Xantphos (4,5-bis(diphenylphosphino)-9,9-dimethyxanthene, 24 mg, 0.041 mmol), and cesium carbonate (112 mg, 0.028 mmol) in dioxane (1 mL) was degassed and refilled with nitrogen (3 times) and then heated at 80° C. overnight. The mixture was diluted with dichloromethane (5 mL) and water (1 mL), and then was filtered through celite. The DCM layer was evaporated under reduced pressure and purified by column chromatography on silica gel (eluting with 0-30% EtOAc/hexanes) to give 1-(3-cyclopropyl-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(4-fluorobenzyl)urea (70 mg, 90% yield) as a clear-white film. MS ESI calc'd. for C36H30FN5O[M+1]+ 568, found 568.

Workup

  1. customwas degassed
  2. additionrefilled with nitrogen (3 times)
  3. additionThe mixture was diluted with dichloromethane (5 mL) and water (1 mL)
  4. filtrationwas filtered through celite
  5. customThe DCM layer was evaporated under reduced pressure
  6. custompurified by column chromatography on silica gel (eluting with 0-30% EtOAc/hexanes)

Sources & evidence

ORD record
ord-45a0eb21516144e29278ff90ea468d56
Source dataset
uspto-grants-2015_05
Patent number
US09023865B2

Reaction notes

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