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 1091728노트

반응식

HRID 1091728 반응식
[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]

참가 물질

4

반응물 1

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

생성물 1

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

시약·촉매·용매 2

HCID 23938Palladium촉매HCID 702Ethanol용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-614adb28d4ef4d019341417b6c90a96f
출처 데이터셋
uspto-grants-2012_03
특허 번호
US08129380B2

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