4-(4-fluoro-3-(4-methoxypiperidine-1-carbonyl)benzyl)-5-nitrophthalazin-1(2H)-one → 8-amino-4-(4-fluoro-3-(4-methoxypiperidine-1-carbonyl)benzyl)phthalazin-1(2H)-one

HRID 1091718Notes

Reaction equation

HRID 1091718 reaction equation
FC1C=CC(CC2C3C(=CC=CC=3[N+]([O-])=O)C(=O)NN=2)=CC=1C(N1CCC(OC)CC1)=O.[F:33][C:34]1[CH:54]=[CH:53][C:37]([CH2:38][C:39]2[C:48]3[C:43](=[C:44]([N+:49]([O-])=O)[CH:45]=[CH:46][CH:47]=3)[C:42](=[O:52])[NH:41][N:40]=2)=[CH:36][C:35]=1[C:55]([N:57]1[CH2:62][CH2:61][CH:60]([O:63][CH3:64])[CH2:59][CH2:58]1)=[O:56]>C(O)C.[Pd]>[NH2:49][C:44]1[CH:45]=[CH:46][CH:47]=[C:48]2[C:43]=1[C:42](=[O:52])[NH:41][N:40]=[C:39]2[CH2:38][C:37]1[CH:53]=[CH:54][C:34]([F:33])=[C:35]([C:55]([N:57]2[CH2:58][CH2:59][CH:60]([O:63][CH3:64])[CH2:61][CH2:62]2)=[O:56])[CH:36]=1

Participants

5

Reactant 2

HCID 577917724-(4-fluoro-3-(4-methoxypiperidine-1-carbonyl)benzyl)-5-nitrophthalazin-1(2H)-oneHCID 577918634-(4-fluoro-3-(4-methoxypiperidine-1-carbonyl)benzyl)-8-nitrophthalazin-1(2H)-one

Product 1

HCID 577917738-amino-4-(4-fluoro-3-(4-methoxypiperidine-1-carbonyl)benzyl)phthalazin-1(2H)-oneYield 60.8%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent2×

Conditions

Temperature
20 °C

Procedure

A mixture of 4-(4-fluoro-3-(4-methoxypiperidine-1-carbonyl)benzyl)-5-nitrophthalazin-1 (2H)-one (34b) with 4-(4-fluoro-3-(4-methoxypiperidine-1-carbonyl)benzyl)-8-nitrophthalazin-1 (2H)-one (34a) (6 mg, 6.81 μmol) in ethanol (2 ml) was added to 5% palladium on carbon (2 mg, 0.94 μmol) in ethanol (5 mL) at 20° C. and the resulting mixture stirred at 20° C. for 5 hours, under an atmosphere of hydrogen. The catalyst was filtered and washed with ethanol and the solvent evaporated to a foam. Further ethanol and 5% palladium on charcoal (10 mg) were added and mixture stirred for a further 5 hours, under an atmosphere of hydrogen. The catalyst was filtered and washed with ethanol. Evaporation gave a gum, which was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford the desired compound as a colourless gum (1.700 mg, 60.8%); 1H NMR (400.132 MHz, CDCl3) δ 1.25-1.31 (1H, m), 1.51-1.82 (2H, m), 1.89-1.98 (1H, m), 3.09-3.17 (1H, m), 3.38 (3H, s), 3.46-3.51 (2H, m), 3.55-3.63 (1H, m), 3.98-4.05 (1H, m), 4.16 (2H, s), 6.43 (2H, s), 6.79 (1H, d), 6.85 (1H, d), 7.00-7.04 (1H, m), 7.25-7.31 (2H, m), 7.41-7.45 (1H, m), 9.56 (1H, s); m/z (LC-MS, ESI+), RT=1.71 (M+H 411.5).

Workup

  1. filtrationThe catalyst was filtered
  2. washwashed with ethanol
  3. customthe solvent evaporated to a foam
  4. additionFurther ethanol and 5% palladium on charcoal (10 mg) were added
  5. stirringmixture stirred for a further 5 hours, under an atmosphere of hydrogen
  6. filtrationThe catalyst was filtered
  7. washwashed with ethanol
  8. customEvaporation
  9. customgave a gum, which
  10. customwas purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length)
  11. additionFractions containing the desired compound
  12. customwere evaporated to dryness

Sources & evidence

ORD record
ord-1c2207f412a340fdacf74a8f1218e4e8
Source dataset
uspto-grants-2012_03
Patent number
US08129380B2

Reaction notes

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