Diisopropylethylamine → 6-Butyl-5-(4-cyclohexyloxy-phenyl)-pyridazine-3-carboxylic acid (8-methyl-8-aza-bicyclo[3.2.1]oct-3-yl)-amide dihydrochloride

HRID 402054

Reaktionsgleichung

Reaktionsgleichung von HRID 402054
[ClH:1].Cl.N1CCOC(CN[C:11]([C:13]2[N:14]=[N:15][C:16]([CH2:32][CH2:33][CH2:34][CH3:35])=[C:17]([C:19]3[CH:24]=[CH:23][C:22]([O:25][CH:26]4[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]4)=[CH:21][CH:20]=3)[CH:18]=2)=[O:12])C1.[CH3:36][N:37]1[CH:42]2[CH2:43][CH2:44][CH:38]1[CH2:39][CH:40]([NH2:45])[CH2:41]2.C(N(C(C)C)C(C)C)C>C1COCC1.C(OCC)C>[ClH:1].[ClH:1].[CH3:36][N:37]1[CH:42]2[CH2:43][CH2:44][CH:38]1[CH2:39][CH:40]([NH:45][C:11]([C:13]1[N:14]=[N:15][C:16]([CH2:32][CH2:33][CH2:34][CH3:35])=[C:17]([C:19]3[CH:24]=[CH:23][C:22]([O:25][CH:26]4[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31]4)=[CH:21][CH:20]=3)[CH:18]=1)=[O:12])[CH2:41]2

Komponenten

6

Edukt 3

HCID 81531DiisopropylethylamineHCID 4083948-Methyl-8-azabicyclo[3.2.1]octan-3-amineHCID 673737226-Butyl-5-(4-cyclohexyloxy-phenyl)-pyridazine-3-carboxylic acid (morpholin-2-ylmethyl)-amide dihydrochloride

Produkt 1

HCID 673748216-Butyl-5-(4-cyclohexyloxy-phenyl)-pyridazine-3-carboxylic acid (8-methyl-8-aza-bicyclo[3.2.1]oct-3-yl)-amide dihydrochloride

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 3283Diethyl EtherLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

A mixture of 6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazine-3-carboxylic acid pentafluorophenyl ester hydrochloride (Example 90, 0.108 mmol, 60 mg), 8-methyl-8-aza-bicyclo[3.2.1]oct-3-ylamine (0.05 mL), ethyl-diisopropyl-amine (0.2 mL) in THF (2.0 mL) may be stirred at room temperature for 3 h. The reaction mixture may be diluted with diethyl ether, washed with water and 2 M aq. sodium hydroxide solution and dried over magnesium sulfate. The crude product may be purified by column chromatography on silica gel using 2-5% 2 M ammonia in MeOH in DCM and treated with 4 N HCl in dioxane. The organic solvents may be removed under reduced pressure, and the product dried overnight under high vacuum to provide the free base of the title compound. 1H NMR (free base, 400 MHz, CDCl3) δ 8.72 (1H, d), 8.09 (1H, s), 7.27 (2H, d), 7.01 (2H, d), 4.30-4.36 (2H, m), 3.20 (2H, bs), 3.08 (2H, t), 2.32 (3H, s), 1.26-2.35 (22H, m), 0.87 (3H, t).

Aufarbeitung

  1. washwashed with water and 2 M aq. sodium hydroxide solution
  2. dry with materialdried over magnesium sulfate
  3. customThe crude product may be purified by column chromatography on silica gel using 2-5% 2 M ammonia in MeOH in DCM
  4. additiontreated with 4 N HCl in dioxane
  5. customThe organic solvents may be removed under reduced pressure
  6. customthe product dried overnight under high vacuum

Quellen und Nachweise

ORD-Eintrag
ord-ac38a5fb5a154fdba62020b7f32c2924
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08741900B2

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