1-(1,3-Dimethyl-1H-pyrazol-4-yl)-8-(6-methoxy-5-nitro-pyridin-3-yl)-3-methyl-1,3-dihydro-imidazo[4,5-c]quinolin-2-one → 8-(5-Amino-6-methoxy-pyridin-3-yl)-1-(1,3-dimethyl-1H-pyrazol-4-yl)-3-methyl-1,3-dihydro-imidazo[4,5-c]quinolin-2-one

HRID 445685Notes

Reaction equation

HRID 445685 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([N:7]2[C:19]3[C:18]4[CH:17]=[C:16]([C:20]5[CH:21]=[N:22][C:23]([O:29][CH3:30])=[C:24]([N+:26]([O-])=O)[CH:25]=5)[CH:15]=[CH:14][C:13]=4[N:12]=[CH:11][C:10]=3[N:9]([CH3:31])[C:8]2=[O:32])[C:4]([CH3:33])=[N:3]1.[H][H]>C1COCC1.CO.[Pd]>[NH2:26][C:24]1[CH:25]=[C:20]([C:16]2[CH:15]=[CH:14][C:13]3[N:12]=[CH:11][C:10]4[N:9]([CH3:31])[C:8](=[O:32])[N:7]([C:5]5[C:4]([CH3:33])=[N:3][N:2]([CH3:1])[CH:6]=5)[C:19]=4[C:18]=3[CH:17]=2)[CH:21]=[N:22][C:23]=1[O:29][CH3:30]

Participants

6

Reactant 2

HCID 596196541-(1,3-Dimethyl-1H-pyrazol-4-yl)-8-(6-methoxy-5-nitro-pyridin-3-yl)-3-methyl-1,3-dihydro-imidazo[4,5-c]quinolin-2-oneHCID 178418361HCID 178418361, compound

Product 1

HCID 596200338-(5-Amino-6-methoxy-pyridin-3-yl)-1-(1,3-dimethyl-1H-pyrazol-4-yl)-3-methyl-1,3-dihydro-imidazo[4,5-c]quinolin-2-one

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 1-(1,3-dimethyl-1H-pyrazol-4-yl)-8-(6-methoxy-5-nitro-pyridin-3-yl)-3-methyl-1,3-dihydro-imidazo[4,5-c]quinolin-2-one (Example 66, 50 mg, 0.112 mmol) in 5 ml THF and 5 ml MeOH was stirred in presence of palladium 10% on charcoal under 1.1 bar of hydrogen for 5 h at rt. The reaction mixture was filtered over Celite and the catalyst was washed with MeOH/THF. The filtrate was evaporated and the crude product was purified by Prep.HPLC (H2O (0.1% TFA)/CH3CN 95:5 to 50:50). The fractions containing products were collected together, basified with NaHCO3, concentrated and extracted with EtOAc (3×). The combined organic layers were dried over Na2SO4, filtered and evaporated to give the title compound as a light yellow solid. (HPLC: tR 2.29 min (Method A); M+H=416 MS-ES; 1H-NMR (d6-DMSO, 400 MHz) 8.94 (s, 1H), 8.12-8.10 (m, 1H), 8.08-8.05 (m, 1H), 7.76-7.72 (m, 1H), 7.47-7.45 (m, 1H), 7.43-7.41 (m, 1H), 7.00-6.97 (m, 11-1), 5.11 (s, br, 2H), 3.92 (s, 3H), 3.89 (s, 3H), 3.57 (s, 3H), 1.94 (s, 3H))

Workup

  1. filtrationThe reaction mixture was filtered over Celite
  2. washthe catalyst was washed with MeOH/THF
  3. customThe filtrate was evaporated
  4. customthe crude product was purified by Prep.HPLC (H2O (0.1% TFA)/CH3CN 95:5 to 50:50)
  5. additionThe fractions containing products
  6. customwere collected together
  7. concentrationconcentrated
  8. extractionextracted with EtOAc (3×)
  9. dry with materialThe combined organic layers were dried over Na2SO4
  10. filtrationfiltered
  11. customevaporated

Sources & evidence

ORD record
ord-d029461b0746407faacaa11338a8fb1b
Source dataset
uspto-grants-2013_07
Patent number
US08476294B2

Reaction notes

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