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

HRID 1887146Notes

Reaction equation

HRID 1887146 reaction equation
[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]

Participants

7

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-d4d843959eb3441dab3cb2dd9318b25e
Source dataset
uspto-grants-2013_08
Patent number
US08501739B2

Reaction notes

Loading…