HCID 59598357, compound → HCID 59598369, compound

HRID 2359702Notes

Reaction equation

HRID 2359702 reaction equation
O[CH:2]([C:28]1[C:37]2[C:32](=[CH:33][C:34]([O:38][CH3:39])=[CH:35][CH:36]=2)[N:31]=[CH:30][CH:29]=1)[C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]([C:12]2[C:13](=[O:27])[N:14]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[N:15]([CH2:18][CH2:19][CH3:20])[C:16]=2[CH3:17])=[O:11])=[CH:5][CH:4]=1>C(O)=O.C(OCC)(=O)C.[Zn]>[CH3:39][O:38][C:34]1[CH:33]=[C:32]2[C:37]([C:28]([CH2:2][C:3]3[CH:4]=[CH:5][C:6]([NH:9][C:10]([C:12]4[C:13](=[O:27])[N:14]([C:21]5[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=5)[N:15]([CH2:18][CH2:19][CH3:20])[C:16]=4[CH3:17])=[O:11])=[CH:7][CH:8]=3)=[CH:29][CH:30]=[N:31]2)=[CH:36][CH:35]=1

Participants

5

Reactant 1

HCID 59598357HCID 59598357, compound

Product 1

HCID 59598369HCID 59598369, compoundYield 25%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 284Formic AcidSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

In a 25 mL round bottom flask was dissolved N-(4-(hydroxy(7-methoxyquinolin-4-yl)methyl)phenyl)-5-methyl-3-oxo-2-phenyl-1-propyl-2,3-dihydro-1H-pyrazole-4-carboxamide (104 mg, 199 μmol) in 4 mL of formic acid and the resultant was then treated with zinc dust (325 mg, 4975 μmol) and heated at 60° C. After 6 h the reaction mixture was diluted with ethyl acetate, filtered over Celite and neutralized with aqueous NaHCO3 (sat). The aqueous phase was extracted with ethyl acetate, and then the organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. The crude mixture was purified by MPLC (ISCO, dichloromethane: 1% NH4OH in MeOH, 100:0 to 90:10) to afford N-(4-((7-methoxyquinolin-4-yl)methyl)phenyl)-5-methyl-3-oxo-2-phenyl-1-propyl-2,3-dihydro-1H-pyrazole-4-carboxamide (25 mg, 25% yield) as an off-white solid. MS (ESI pos. ion) m/z: 507 (MH+). Calc'd exact mass for C31H30N4O3: 506. 1H NMR (400 MHz, DMSO-d6) 10.65 (s, 1H), 8.74 (d, J=4.42 Hz, 1H), 8.10 (d, J=9.22 Hz, 1H), 7.57 (t, J=7.52 Hz, 2H), 7.46-7.52 (m, 3H), 7.35-7.44 (m, 3H), 7.14-7.28 (m, 4H), 4.38 (s, 2H), 3.90 (s, 3H), 3.79 (t, J=7.14 Hz, 2H), 2.72 (s, 3H), 1.32-1.41 (m, 2H), 0.66 (t, J=7.39 Hz, 3H).

Workup

  1. filtrationfiltered over Celite
  2. extractionThe aqueous phase was extracted with ethyl acetate
  3. dry with materialthe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude mixture was purified by MPLC (ISCO, dichloromethane: 1% NH4OH in MeOH, 100:0 to 90:10)

Sources & evidence

ORD record
ord-6f97253b66944d98b992c8c05f638554
Source dataset
uspto-grants-2014_04
Patent number
US08685983B2

Reaction notes

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