Cesium carbonate → 1-(3-(methylamino)-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(phenyl(tetrahydrofuran-2-yl)methyl)urea

HRID 590853Notes

Reaction equation

HRID 590853 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]2[C:8]([NH:30][CH3:31])=[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.[C:32]1([CH:38]([CH:43]2[CH2:47][CH2:46][CH2:45][O:44]2)[NH:39][C:40]([NH2:42])=[O:41])[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=C(OC)C=CC=2OC)=C(C(C)C)C=1)C.C1C=[C-]C(CCN)=CC=1.Cl[Pd+].O1CCOCC1.CCOC(C)=O>[CH3:31][NH:30][C:8]1[C:5]2[CH:6]=[N:7][C:2]([NH:42][C:40]([NH:39][CH:38]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[CH:43]3[CH2:47][CH2:46][CH2:45][O:44]3)=[O:41])=[CH:3][C:4]=2[N:10]([C:11]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[N:9]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 1182717571-(Phenyl(tetrahydrofuran-2-yl)methyl)ureaHCID 1182724066-chloro-N-methyl-1-trityl-1H-pyrazolo[4,3-c]pyridin-3-amine

Product 1

HCID 1182722511-(3-(methylamino)-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(phenyl(tetrahydrofuran-2-yl)methyl)urea

Reagents, catalysts & solvents 3

HCID 25112666BrettPhos PalladacycleCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

6-chloro-N-methyl-1-trityl-1H-pyrazolo[4,3-c]pyridin-3-amine (400 mg, 0.941 mmol), 1-(phenyl(tetrahydrofuran-2-yl)methyl)urea (228 mg, 1.035 mmol), cesium carbonate (920 mg, 2.82 mmol) and BrettPhos precatalyst (52.6 mg, 0.066 mmol) were taken up in dioxane (9.5 ml) in a 20 mL microwave vial. The vial was evacuated and back-filled with N2 (×3). The reaction mixture was stirred at 100° C. for two hours. Room temperature was attained. The crude reaction mixture was diluted with EtOAc and filtered through celite. The filtrate was concentrated in vacuo, taken up in 5 ml of DCM, and purified on silica gel 5-50% DCM/EtOAc to give 1-(3-(methylamino)-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(phenyl(tetrahydrofuran-2-yl)methyl)urea. MS ESI calc'd. for C38H37N6O2 [M+H]+ 609. found 609.

Workup

  1. customThe vial was evacuated
  2. additionback-filled with N2 (×3)
  3. customRoom temperature
  4. customThe crude reaction mixture
  5. filtrationfiltered through celite
  6. concentrationThe filtrate was concentrated in vacuo
  7. custompurified on silica gel 5-50% DCM/EtOAc

Sources & evidence

ORD record
ord-b7386dca42fa491a9c416b6f4f663130
Source dataset
uspto-grants-2016_01
Patent number
US09233979B2

Reaction notes

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