Isoamylamine → 6-[4-(5-Fluoro-2-trifluoromethylbenzoyl)piperazin-1-YL]imidazo[1,2-B]pyridazine-2-carboxylic acid (3-methylbutyl)amide

HRID 1985640Notes

Reaction equation

HRID 1985640 reaction equation
C([O:3][C:4]([C:6]1[N:7]=[C:8]2[CH:13]=[CH:12][C:11]([N:14]3[CH2:19][CH2:18][N:17]([C:20](=[O:32])[C:21]4[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:22]=4[C:28]([F:31])([F:30])[F:29])[CH2:16][CH2:15]3)=[N:10][N:9]2[CH:33]=1)=O)C.[CH2:34]([NH2:39])[CH2:35][CH:36]([CH3:38])[CH3:37].[C-]#N.[Na+]>>[CH3:37][CH:36]([CH3:38])[CH2:35][CH2:34][NH:39][C:4]([C:6]1[N:7]=[C:8]2[CH:13]=[CH:12][C:11]([N:14]3[CH2:15][CH2:16][N:17]([C:20](=[O:32])[C:21]4[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:22]=4[C:28]([F:31])([F:30])[F:29])[CH2:18][CH2:19]3)=[N:10][N:9]2[CH:33]=1)=[O:3]

Participants

4

Reactant 3

HCID 7894IsoamylamineHCID 8929Sodium CyanideHCID 668634596-[4-(5-Fluoro-2-trifluoromethylbenzoyl)piperazin-1-YL]imidazo[1,2-B]pyridazine-2-carboxylic acid ethyl ester

Product 1

HCID 117061156-[4-(5-Fluoro-2-trifluoromethylbenzoyl)piperazin-1-YL]imidazo[1,2-B]pyridazine-2-carboxylic acid (3-methylbutyl)amideYield 85%

Procedure

A mixture of 6-[4-(5-fluoro-2-trifluoromethylbenzoyl)piperazin-1-yl]imidazo[1,2-b]pyridazine-2-carboxylic acid ethyl ester (0.100 g, 0.215 mmol), isoamylamine (1 mL), and sodium cyanide (0.020 g, 0.408 mmol) was stirred at room temperature over night. The reaction mixture was concentrated in vacuo, diluted with ethyl acetate and washed with water. The organic layer was dried over anhydrous Na2SO4, concentrated. The residue was purified by column chromatography. The title compound was obtained as a white solid in 85% yield (0.092 g). 1H NMR (300 MHz, CDCl3) δ 8.13 (s, 1H), 7.74-7.7 (m, 1H), 7.65 (d, J=9.9 Hz, 1H), 7.21-7.16 (m, 1H), 6.86 (d, J=9.9 Hz, 1H), 4.02-3.92 (m, 1H), 3.89-3.79 (m, 1H), 3.62-3.54 (m, 2H), 3.49-3.39 (m, 4H), 3.35-3.28 (m, 2H), 1.74-1.6 (m, 1H), 1.53-1.44 (m, 2H), 0.91 (d, J=6.6 Hz, 6H). 13C NMR (75 MHz, CDCl3) δ 165.9, 162.5, 162.4, 154.7, 138.4, 137.0, 136.9, 135.6, 129.7, 129.6, 129.5, 126.4, 125.1, 123.3, 122.9, 122.4, 121.4, 118.1, 116.8, 116.5, 114.9, 114.6, 111.8, 46.2, 46.1, 45.6, 41.2, 38.5, 37.3, 25.7, 22.4. MS (ES+) m/z 507 (M+1).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. additiondiluted with ethyl acetate
  3. washwashed with water
  4. dry with materialThe organic layer was dried over anhydrous Na2SO4
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-2cb73622b05646e9bc0dfb8c25b951ea
Source dataset
uspto-grants-2009_06
Patent number
US07547698B2

Reaction notes

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