Potassium Phosphate, Tribasic → (R)-ethyl 2-benzyl-3-oxo-6-(3-(1-phenylethyl)ureido)-2,3-dihydro-1H-pyrazolo[4,3-c]pyridine-1-carboxylate

HRID 588172Notes

Reaction equation

HRID 588172 reaction equation
[CH2:1]([N:8]1[C:17](=[O:18])[C:11]2[CH:12]=[N:13][C:14](Cl)=[CH:15][C:10]=2[N:9]1[C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:24]1([C@H:30]([NH:32][C:33]([NH2:35])=[O:34])[CH3:31])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.CC(P(C(C)(C)C)C1N(C2C(C3C=CC=CC=3)=NN(C3C=CC=CC=3)C=2C2C=CC=CC=2)N=CC=1)(C)C.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>COCCOC.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:1]([N:8]1[C:17](=[O:18])[C:11]2[CH:12]=[N:13][C:14]([NH:35][C:33]([NH:32][C@@H:30]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH3:31])=[O:34])=[CH:15][C:10]=2[N:9]1[C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 11547931BippyPhosHCID 13013340(R)-1-(1-phenylethyl)ureaHCID 118271800ethyl 2-benzyl-6-chloro-3-oxo-2,3-dihydro-1H-pyrazolo[4,3-c]pyridine-1-carboxylate2×

Product 1

HCID 118373953(R)-ethyl 2-benzyl-3-oxo-6-(3-(1-phenylethyl)ureido)-2,3-dihydro-1H-pyrazolo[4,3-c]pyridine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

Ethyl 2-benzyl-6-chloro-3-oxo-2,3-dihydro-1H-pyrazolo[4,3-c]pyridine-1-carboxylate (Intermediate 12B; 71 mg, 0.214 mmol), (R)-1-(1-phenylethyl)urea (45 mg, 0.274 mmol), bippyphos (13.2 mg, 0.026 mmol), Pd2(dba)3 (5.4 mg, 5.90 μmol), and tripotassium phosphate (74 mg, 0.349 mmol) were taken up in DME (2 mL) in a 5 mL microwave vial. The vial was evacuated and back-filled with N2 (×3) and the reaction stirred at 85° C. for 2 h. Room temperature was attained and the reaction mixture filtered through Celite, eluting with MeCN. Purification of the residue by flash chromatography (12-100% EtOAc-hexanes) gave (R)-ethyl 2-benzyl-3-oxo-6-(3-(1-phenylethyl)ureido)-2,3-dihydro-1H-pyrazolo[4,3-c]pyridine-1-carboxylate. MS ESI calc'd. For C25H25N5O4 [M+1]+ 460. found 460.

Workup

  1. customThe vial was evacuated
  2. additionback-filled with N2 (×3)
  3. customRoom temperature
  4. filtrationthe reaction mixture filtered through Celite
  5. washeluting with MeCN
  6. customPurification of the residue by flash chromatography (12-100% EtOAc-hexanes)

Sources & evidence

ORD record
ord-878bfc84fbec4d8283fa49b414a7cbd5
Source dataset
uspto-grants-2016_01
Patent number
US09226922B2

Reaction notes

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