2-Chloropropane → 1-Isopropyl-4-[6-(4-trifluoromethylphenyl)pyridazin-3-yl]-[1,4]diazepane, dihydrochloride

HRID 80910

Reaktionsgleichung

Reaktionsgleichung von HRID 80910
[ClH:1].Cl.[F:3][C:4]([F:25])([F:24])[C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:16]=[N:15][C:14]([N:17]3[CH2:23][CH2:22][CH2:21][NH:20][CH2:19][CH2:18]3)=[CH:13][CH:12]=2)=[CH:7][CH:6]=1.C(N(CC)CC)C.[H-].[Na+].[Cl:35][CH:36]([CH3:38])[CH3:37]>C1COCC1.CN(C)C=O>[ClH:35].[ClH:1].[CH:36]([N:20]1[CH2:21][CH2:22][CH2:23][N:17]([C:14]2[N:15]=[N:16][C:11]([C:8]3[CH:9]=[CH:10][C:5]([C:4]([F:24])([F:3])[F:25])=[CH:6][CH:7]=3)=[CH:12][CH:13]=2)[CH2:18][CH2:19]1)([CH3:38])[CH3:37]

Komponenten

7

Edukt 4

HCID 63612-ChloropropaneHCID 8471TriethylamineHCID 24758Sodium hydrideHCID 1317307784-[6-(4-Trifluoromethylphenyl)pyridazin-3-yl][1,4]diazepane, dihydrochloride

Produkt 1

HCID 1317307771-Isopropyl-4-[6-(4-trifluoromethylphenyl)pyridazin-3-yl]-[1,4]diazepane, dihydrochlorideAusbeute 21 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

4-[6-(4-Trifluoromethylphenyl)pyridazin-3-yl][1,4]diazepane, dihydrochloride (0.028 g, 0.071 mmol) was suspended in THF (4 mL) and triethylamine (0.022 g, 0.21 mmol) was added. Sodium hydride (0.0085 g, 0.35 mmol) was added and the reaction mixture was stirred at rt for 20 min. Dry N,N-dimethylformamide (1 mL) and 2-chloropropane (0.056 g, 0.71 mmol) was added and the reaction mixture was heated 30 min at 160° C. and 30 min at 180° C. in a microwave oven. The reaction mixture was purified on a silicagel column (0.04-0.063 mesh) using dichloromethane/MeOH (9:1) as eluent. This afforded a crude oil containing several components that was purified further by preparative HPLC using Method B. This afforded 9 mg of an oil which was dissolved into MeOH. Addition of HCl in diethyl ether afforded 6.5 mg (21%) of the title compound as an oily dihydrochloride.

Aufarbeitung

  1. temperaturethe reaction mixture was heated 30 min at 160° C. and 30 min at 180° C. in a microwave oven
  2. customThe reaction mixture was purified on a silicagel column (0.04-0.063 mesh)
  3. customThis afforded a crude oil
  4. additioncontaining several components that
  5. customwas purified further by preparative HPLC
  6. dissolutionThis afforded 9 mg of an oil which was dissolved into MeOH
  7. additionAddition of HCl in diethyl ether

Quellen und Nachweise

ORD-Eintrag
ord-48faf4b9d2b044d9ba597e68eb6d8c3d
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08846677B2

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