Potassium Carbonate → 6-[4-(3,3-Difluoro-2-oxo-2,3-dihydroindol-1-YL)piperidin-1-YL]pyridazine-3-carboxylic acid (3-cyclopropylpropyl)amide

HRID 552157Notes

Reaction equation

HRID 552157 reaction equation
[F:1][C:2]1([F:18])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]([CH:11]2[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)[C:3]1=[O:17].[CH:19]1([CH2:22][CH2:23][CH2:24][NH:25][C:26]([C:28]2[N:29]=[N:30][C:31](Cl)=[CH:32][CH:33]=2)=[O:27])[CH2:21][CH2:20]1.C([O-])([O-])=O.[K+].[K+]>[N+](CCCC)(CCCC)(CCCC)CCCC.[I-].O1CCOCC1>[CH:19]1([CH2:22][CH2:23][CH2:24][NH:25][C:26]([C:28]2[N:29]=[N:30][C:31]([N:14]3[CH2:13][CH2:12][CH:11]([N:4]4[C:5]5[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=5)[C:2]([F:1])([F:18])[C:3]4=[O:17])[CH2:16][CH2:15]3)=[CH:32][CH:33]=2)=[O:27])[CH2:21][CH2:20]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 671722233,3-Difluoro-1-piperidin-4-yl-1,3-dihydroindol-2-oneHCID 860259516-Chloropyridazine-3-carboxylic acid (3-cyclopropylpropyl)amide

Product 1

HCID 671720966-[4-(3,3-Difluoro-2-oxo-2,3-dihydroindol-1-YL)piperidin-1-YL]pyridazine-3-carboxylic acid (3-cyclopropylpropyl)amideYield 60%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 3,3-difluoro-1-piperidin-4-yl-1,3-dihydroindol-2-one (0.180 g, 0.71 mmol), 6-chloropyridazine-3-carboxylic acid (3-cyclopropylpropyl)amide (0.160 g, 0.66 mmol), K2CO3 (0.150 g, 1.08 mmol) and n-Bu4NI (10 mg) in dioxane (10 mL) was heated to reflux overnight, then concentrated. The residue was purified by flash chromatography to yield the title compound as a white powder in 60% yield (0.183 g). m.p. 51-53° C. 1H NMR (300 MHz, CDCl3) δ 7.97 (d, J=9.3 Hz, 1H), 7.86 (s, br, 1H), 7.50 (d, J=6.6 Hz, 1H), 7.12-6.91 (m, 3H), 4.66 (d, J=12.9 Hz, 2H), 4.35 (s, br, 1H), 3.46-3.42 (m, 2H), 3.09 (t, J=12.9 Hz, 2H), 2.52-2.35 (m, 2H), 1.90 (d, J=11.4 Hz, 2H), 1.69-1.65 (m, 2H), 1.28-1.23 (m, 2H), 0.72-0.55 (m, 1H), 0.48-0.25 (m, 2H), 0.08-−0.07 (m, 2H.); 13C NMR (75 MHz, CDCl3) δ 165.1, 163.1, 159.7, 144.9, 142.4, 133.4, 127.0, 125.1, 123.7, 120.3, 112.3, 110.7, 106.9, 50.9, 44.6, 39.1, 35.1, 29.5, 28.3, 27.5, 26.1, 10.4, 4.4. MS (ES+) m/z 456.3 (M+1).

Workup

  1. temperaturewas heated
  2. temperatureto reflux overnight
  3. concentrationconcentrated
  4. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-47e8b13e1cbd44b5906345e791e13685
Source dataset
uspto-grants-2011_05
Patent number
US07951805B2

Reaction notes

Loading…