Diisopropylethylamine → 4-(3-(5-cyclopropylpyridin-2-yloxy)benzylidene)-N-(pyridazin-3-yl)piperidine-1-carboxamide

HRID 1666387Notes

Reaction equation

HRID 1666387 reaction equation
FC(F)(F)C(O)=O.[CH:8]1([C:11]2[CH:12]=[CH:13][C:14]([O:17][C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([CH:24]=[C:25]4[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]4)[CH:19]=3)=[N:15][CH:16]=2)[CH2:10][CH2:9]1.[N:31]1[CH:36]=[CH:35][CH:34]=[C:33]([NH:37][C:38](=O)[O:39]C2C=CC=CC=2)[N:32]=1.C(N(C(C)C)CC)(C)C>CC#N>[CH:8]1([C:11]2[CH:12]=[CH:13][C:14]([O:17][C:18]3[CH:19]=[C:20]([CH:21]=[CH:22][CH:23]=3)[CH:24]=[C:25]3[CH2:30][CH2:29][N:28]([C:38]([NH:37][C:33]4[N:32]=[N:31][CH:36]=[CH:35][CH:34]=4)=[O:39])[CH2:27][CH2:26]3)=[N:15][CH:16]=2)[CH2:10][CH2:9]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 20150036Phenyl pyridazin-3-ylcarbamateHCID 668761235-Cyclopropyl-2-(3-(piperidin-4-ylidenemethyl)phenoxy)pyridine trifluoroacetate

Product 1

HCID 533165504-(3-(5-cyclopropylpyridin-2-yloxy)benzylidene)-N-(pyridazin-3-yl)piperidine-1-carboxamideYield 87.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 5-cyclopropyl-2-(3-(piperidin-4-ylidenemethyl)phenoxy)pyridine trifluoroacetate (0.972 g, 3.17 mmol) in CH3CN (10 mL) was added phenyl pyridazin-3-ylcarbamate (0.751 g, 3.49 mmol) followed by diisopropylethylamine (2.76 mL, 15.9 mmol). The reaction was stirred at room temperature for 3 d. The reaction mixture was concentrated and the residue was purified by silica gel column chromatography (0-15% EtOH/CH2Cl2) to afford the title compound as a white foam (1.19 g). Recrystallization from hot diisopropyl ether with a few drops of methanol afforded the title compound as an off-white solid (0.857 g, 63% yield). MS (APCI 10V) AP+2 428.09; 1H NMR (400 MHz, CDCl3) δ ppm 0.61-0.67 (m, 2H) 0.93-0.99 (m, 2H) 1.82-1.90 (m, 1H) 2.45 (t, 2H) 2.59 (t, 2H) 3.54 (t, 2H) 3.64 (t, 2H) 6.39 (s, 1H) 6.79-6.82 (m, 1H) 6.92-6.96 (m, 1H) 6.96-7.01 (m, 2H) 7.30-7.35 (m, 2H) 7.38-7.42 (m, 1H) 7.73 (br. s., 1H) 8.01 (d, 1H) 8.29 (d, 1H) 8.82 (d, 1H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customthe residue was purified by silica gel column chromatography (0-15% EtOH/CH2Cl2)

Sources & evidence

ORD record
ord-7e17e6a6b21b4ce5b359b3cbd2c9c2a8
Source dataset
uspto-grants-2011_10
Patent number
US08044052B2

Reaction notes

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