Hydrazine hydrate (1:1) → 4-(3-(4-ethoxypiperidine-1-carbonyl)-4-fluorobenzyl)-5,6,7-trimethyl-2,6-dihydro-1H-pyrrolo[3,4-d]pyridazin-1-one

HRID 1091740Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1091740
O.[NH2:2][NH2:3].[CH2:4]([O:6][CH:7]1[CH2:12][CH2:11][N:10]([C:13]([C:15]2[CH:16]=[C:17]([CH2:22][C:23]([C:25]3[C:26]([C:33]([O:35]C)=O)=[C:27]([CH3:32])[N:28]([CH3:31])[C:29]=3[CH3:30])=O)[CH:18]=[CH:19][C:20]=2[F:21])=[O:14])[CH2:9][CH2:8]1)[CH3:5]>C(O)(=O)C>[CH2:4]([O:6][CH:7]1[CH2:8][CH2:9][N:10]([C:13]([C:15]2[CH:16]=[C:17]([CH:18]=[CH:19][C:20]=2[F:21])[CH2:22][C:23]2[C:25]3[C:26](=[C:27]([CH3:32])[N:28]([CH3:31])[C:29]=3[CH3:30])[C:33](=[O:35])[NH:2][N:3]=2)=[O:14])[CH2:11][CH2:12]1)[CH3:5]

Komponenten

4

Edukt 2

HCID 24654Hydrazine hydrate (1:1)HCID 57791827Methyl 4-(2-(3-(4-ethoxypiperidine-1-carbonyl)-4-fluorophenyl)acetyl)-1,2,5-trimethyl-1H-pyrrole-3-carboxylate

Produkt 1

HCID 577917774-(3-(4-ethoxypiperidine-1-carbonyl)-4-fluorobenzyl)-5,6,7-trimethyl-2,6-dihydro-1H-pyrrolo[3,4-d]pyridazin-1-oneAusbeute 32,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 176Acetic AcidLösungsmittel

Versuchsvorschrift

Hydrazine hydrate (0.028 mL, 0.38 mmol) was added to methyl 4-(2-(3-(4-ethoxypiperidine-1-carbonyl)-4-fluorophenyl)acetyl)-1,2,5-trimethyl-1H-pyrrole-3-carboxylate (55) (0.158 g, 0.34 mmol) in acetic acid (4 mL). The resulting solution was stirred at room temperature for 2 days. The resulting mixture was evaporated to dryness and the residue was azeotroped with toluene to afford the crude product, 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 (0.049 g, 32.3% yield); 1H NMR (400.132 MHz, DMSO) δ 1.11 (3H, t), 1.29 (1H, m), 1.41 (1H, m), 1.72 (1H, m), 1.86 (1H, m), 2.29 (3H, s), 2.60 (3H, s), 3.05 (1H, m), 3.28 (3H, s), 3.46 (2H, m), 3.53 (3H, s), 3.96 (1H, m), 4.12 (2H, s), 7.16-7.28 (3H, m), 11.17 (1H, s); m/z (LC-MS, ESI+), RT=1.78 min (M+H=441.11).

Aufarbeitung

  1. customThe resulting mixture was evaporated to dryness
  2. customthe residue was azeotroped with toluene
  3. customto afford the crude product, which
  4. customwas 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

Quellen und Nachweise

ORD-Eintrag
ord-0e198fc6d4fa46c4a0e8f20a5508e665
Quelldatensatz
uspto-grants-2012_03
Patentnummer
US08129380B2

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