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

HRID 1091728Notes

Reaction equation

HRID 1091728 reaction equation
[F:1][C:2]1[CH:22]=[CH:21][C:5]([CH2:6][C:7]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][C:15]=3[N+:17]([O-])=O)[C:10](=[O:20])[NH:9][N:8]=2)=[CH:4][C:3]=1[C:23]([N:25]1[CH2:30][CH2:29][CH:28]([O:31][CH3:32])[CH2:27][CH2:26]1)=[O:24]>[Pd].C(O)C>[NH2:17][C:15]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:16]=1[C:7]([CH2:6][C:5]1[CH:21]=[CH:22][C:2]([F:1])=[C:3]([C:23]([N:25]3[CH2:30][CH2:29][CH:28]([O:31][CH3:32])[CH2:27][CH2:26]3)=[O:24])[CH:4]=1)=[N:8][NH:9][C:10]2=[O:20]

Participants

4

Reactant 1

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

Product 1

HCID 577918455-amino-4-(4-fluoro-3-(4-methoxypiperidine-1-carbonyl)benzyl)phthalazin-1(2H)-oneYield 29.8%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

4-(4-fluoro-3-(4-methoxypiperidine-1-carbonyl)benzyl)-5-nitrophthalazin-1 (2H)-one (45) (40 mg, 0.09 mmol) was added to 5% palladium on carbon (4 mg, 0.04 mmol) in ethanol (7 ml) at 25° C. under air. The resulting mixture was hydrogenated at 25° C. for 22 hours. The catalyst was filtered and washed with ethanol and the solvent evaporated to a pale brown gum. The crude product 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 material as a beige solid (11 mg, 29.5% yield); 1H NMR (400.132 MHz, DMSO) δ 1.66-1.81 (2H, m), 1.86-1.96 (2H, m), 3.10-3.19 (1H, m), 3.36 (3H, s), 3.44-3.50 (2H, m), 3.55-3.64 (1H, m), 3.91-3.99 (1H, m), 4.08 (2H, s), 4.44 (2H, s), 6.99 (1H, d), 7.05-7.10 (1H, m), 7.23-7.28 (2H, m), 7.50-7.54 (1H, m), 7.94 (1H, d), 9.95 (1H, s); m/z (LC-MS, ESI+), RT=1.50 (M+H 411.3).

Workup

  1. filtrationThe catalyst was filtered
  2. washwashed with ethanol
  3. customthe solvent evaporated to a pale brown gum
  4. customThe crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length)
  5. additionFractions containing the desired compound
  6. customwere evaporated to dryness

Sources & evidence

ORD record
ord-614adb28d4ef4d019341417b6c90a96f
Source dataset
uspto-grants-2012_03
Patent number
US08129380B2

Reaction notes

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