Hydrochloric Acid → HCID 67373292, Verbindung

HRID 2168727Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2168727
[ClH:1].Cl.[CH2:3]([C:7]1[N:8]=[N:9][C:10]([O:31][CH:32]2[CH2:37][CH2:36][N:35]([CH3:38])[CH2:34][CH2:33]2)=[CH:11][C:12]=1[C:13]1[CH:14]=[CH:15][C:16]([O:24][CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]2)=[C:17]([NH:19][S:20]([CH3:23])(=[O:22])=[O:21])[CH:18]=1)[CH2:4][CH2:5][CH3:6].[CH2:39](Br)[CH:40]([CH3:42])[CH3:41].C(=O)([O-])[O-].[K+].[K+].Cl>CN(C=O)C.O.CCOC(C)=O.C(Cl)Cl.CCOCC>[ClH:1].[ClH:1].[CH2:3]([C:7]1[N:8]=[N:9][C:10]([O:31][CH:32]2[CH2:37][CH2:36][N:35]([CH3:38])[CH2:34][CH2:33]2)=[CH:11][C:12]=1[C:13]1[CH:14]=[CH:15][C:16]([O:24][CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]2)=[C:17]([N:19]([CH2:39][CH:40]([CH3:42])[CH3:41])[S:20]([CH3:23])(=[O:21])=[O:22])[CH:18]=1)[CH2:4][CH2:5][CH3:6]

Komponenten

9

Edukt 4

HCID 313Hydrochloric AcidHCID 65551-Bromo-2-methylpropaneHCID 11430Potassium CarbonateHCID 67374404HCID 67374404, Verbindung

Produkt 1

HCID 67373292HCID 67373292, VerbindungAusbeute 117,7 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 3283Diethyl EtherLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 22728543Water ethylacetateLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

To a solution of N-{5-[3-butyl-6-(1-methyl-piperidin-4-yloxy)-pyridazin-4-yl]-2-cyclohexyloxy-phenyl}-methanesulfonamide dihydrochloride (0.1 mmol, 59 mg) in DMF (1.0 mL) was added isobutyl bromide (0.2 mmol, 22 μL), and potassium carbonate (0.4 mmol, 56 mg). And the mixture was stirred at 90° C. for 2 hours. It was then diluted with water/EtOAc. The solvent was removed in vacuo and the residue was purified by silica gel chromatography (DCM to DCM+10% 2N NH3 in MeOH) to give a colorless sticky solid, which was dissolved in DCM (1.0 mL), 2N HCl in ether (1.0 mL) was added, condensed, triturated with hexanes to provide the title compound (38 mg). LCMS: m/z 574 [M+1]. 1H NMR (400 MHz, CD3OD): δ 7.39 (1 H, d), 7.31 (1 H, s), 7.25 (1 H, d), 7.04 (1 H, s), 5.42 (1 H, bs), 4.46-4.53 (1 H, m), 3.42-3.48 (1 H, m), 2.98-3.30 (5 H, m), 2.95 (3 H, s), 2.90-2.94 (2 H, m), 2.69 (3 H, s), 2.09-2.30 (6 H, m), 1.82-1.88 (2H, m), 1.20-1.69 (11 H, m), 0.89-0.93 (6 H, m), 0.79 (3 H, t).

Aufarbeitung

  1. customThe solvent was removed in vacuo
  2. customthe residue was purified by silica gel chromatography (DCM to DCM+10% 2N NH3 in MeOH)
  3. customto give a colorless sticky solid, which
  4. customcondensed
  5. customtriturated with hexanes

Quellen und Nachweise

ORD-Eintrag
ord-feab5424841f400887bec79dd85a009b
Quelldatensatz
uspto-grants-2015_06
Patentnummer
US09045461B2

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