Diisopropylethylamine → 6-((1-(3-Fluoro-5-(trifluoromethyl)benzyl)piperidin-4-yl)amino)pyridazine-3-carbonitrile

HRID 1258157Notes

Reaction equation

HRID 1258157 reaction equation
Cl[C:2]1[N:7]=[N:6][C:5]([C:8]#[N:9])=[CH:4][CH:3]=1.[F:10][C:11]1[CH:12]=[C:13]([CH:22]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:24]=1)[CH2:14][N:15]1[CH2:20][CH2:19][CH:18]([NH2:21])[CH2:17][CH2:16]1.C(N(C(C)C)CC)(C)C>C(#N)C.ClCCl>[F:10][C:11]1[CH:12]=[C:13]([CH:22]=[C:23]([C:25]([F:28])([F:26])[F:27])[CH:24]=1)[CH2:14][N:15]1[CH2:20][CH2:19][CH:18]([NH:21][C:2]2[N:7]=[N:6][C:5]([C:8]#[N:9])=[CH:4][CH:3]=2)[CH2:17][CH2:16]1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 133828716-Chloropyridazine-3-carbonitrileHCID 532561571-(3-Fluoro-5-trifluoromethyl-benzyl)-piperidin-4-ylamine

Product 1

HCID 249891986-((1-(3-Fluoro-5-(trifluoromethyl)benzyl)piperidin-4-yl)amino)pyridazine-3-carbonitrileYield 80.5%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 6-chloro-pyridazine-3-carbonitrile (D4) (1.39 g, 9.95 mmol), 1-(3-fluoro-5-trifluoromethyl-benzyl)-piperidin-4-ylamine (D7) (2.5 g, 9.04 mmol) and diisopropylethylamine (2.63 ml, 14.92 mmol) in acetonitrile (2 ml) was stirred at 120° C. for 30 min, under microwave irradiation ((Biotage MW-oven). The mixture was then diluted with dichloromethane (50 ml) and extracted with a saturated solution of sodium carbonate. The organic layer was separated, dried (Na2SO4), filtered, evaporated in vacuo and the residue purified by column chromatography (silica gel; 0-2.5% ammonia in methanol (7M)/dichloromethane). The desired fractions were collected and evaporated in vacuo. The residue precipitated from diisopropylether to yield E17 (2.76 g, 73%) as a solid. C18H17F4N5 requires 379. Found 380 (MH+); mp: 151.4° C.

Workup

  1. extractionextracted with a saturated solution of sodium carbonate
  2. customThe organic layer was separated
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customthe residue purified by column chromatography (silica gel; 0-2.5% ammonia in methanol (7M)/dichloromethane)
  7. customThe desired fractions were collected
  8. customevaporated in vacuo
  9. customThe residue precipitated from diisopropylether

Sources & evidence

ORD record
ord-1ba884f371b745969ada46dcb27749b5
Source dataset
uspto-grants-2013_06
Patent number
US08466153B2

Reaction notes

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