1,8-Diazabicyclo(5.4.0)undec-7-ene → 6-(1-Benzylpiperidin-4-ylamino)pyridazine-3-carboxylic acid pentylamide

HRID 1171806Notes

Reaction equation

HRID 1171806 reaction equation
N[C:2]1[CH:14]=[CH:13][C:5]([CH2:6][N:7]2[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]2)=[CH:4][CH:3]=1.[CH2:15]([NH:20][C:21]([C:23]1[N:24]=[N:25][C:26](Cl)=[CH:27][CH:28]=1)=[O:22])[CH2:16][CH2:17][CH2:18][CH3:19].[N:30]12CCCN=C1CCCCC2>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C=O)C.C(OCC)(=O)C>[CH2:15]([NH:20][C:21]([C:23]1[N:24]=[N:25][C:26]([NH:30][CH:10]2[CH2:11][CH2:12][N:7]([CH2:6][C:5]3[CH:13]=[CH:14][CH:2]=[CH:3][CH:4]=3)[CH2:8][CH2:9]2)=[CH:27][CH:28]=1)=[O:22])[CH2:16][CH2:17][CH2:18][CH3:19]

Participants

7

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 8461504-(Piperidin-1-ylmethyl)anilineHCID 442031536-Chloropyridazine-3-carboxylic acid pentylamide

Product 1

HCID 116178646-(1-Benzylpiperidin-4-ylamino)pyridazine-3-carboxylic acid pentylamideYield 27%

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 4-aminobenzylpiperidine (0.460 g, 2.42 mmol), 6-chloropyridazine-3-carboxylic acid pentylamide (0.500 g, 2.20 mmol) and tetrabutylammonium bromide (0.071 g, 10 mole %) in DMF (5 mL) was added 1,8-diazabicyclo[5,4,0]undec-7-ene (0.66 mL, 4.40 mmol). The brown reaction mixture was heated at 80° C. for 24 hours. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (50 mL), washed with water, dried over Na2SO4, filtered, and concentrated. The crude material was subjected to column chromatography to afford the title compound as a brown solid in 27% yield (0.238 g). 1H NMR (300 MHz, CDCl3) δ 7.92 (d, J=9.3 Hz, 1H), 7.87 (t, J=5.7 Hz, 1H), 7.31-7.20 (m, 6H), 6.65 (d, J=9.3 Hz, 1H), 4.91 (d, J=7.5 Hz, 1H), 3.91 (m, 1H), 3.51 (s, 2H), 3.42 (q, J=7.2 Hz, 2H), 2.86 (m, 2H), 2.21-2.06 (m, 4H), 1.64-1.54 (m, 4H), 1.37-1.28 (m, 4H), 0.91-0.85 (m, 3H). 13C NMR (75 MHz, CDCl3) δ 163.3, 159.1, 145.2, 138.3, 129.1, 128.3, 127.1, 126.8, 113.7, 63.1, 52.2, 48.8, 39.4, 32.2, 29.3, 29.1, 22.4, 14.0. MS (ES+) m/z 380 (M+1).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. washwashed with water
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-e6083a969f39470291adba85de1253e8
Source dataset
uspto-grants-2010_11
Patent number
US07829712B2

Reaction notes

Loading…