Diethyl Ether → (4-Isopropyl-piperazin-1-yl)-(6-piperidin-1-ylmethyl-pyridin-3-yl)-methanone

HRID 30453

Reaction equation

HRID 30453 reaction equation
CO[C:3](=[O:17])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][N:11]2[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)=[N:6][CH:5]=1.[Mg+2].[Br-].[Br-].O(CC)CC.[CH:26]([N:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1)([CH3:28])[CH3:27]>C1COCC1>[NH3:6].[CH:26]([N:29]1[CH2:34][CH2:33][N:32]([C:3]([C:4]2[CH:5]=[N:6][C:7]([CH2:10][N:11]3[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16]3)=[CH:8][CH:9]=2)=[O:17])[CH2:31][CH2:30]1)([CH3:28])[CH3:27]

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 780131-IsopropylpiperazineHCID 82241Magnesium BromideHCID 44515770Methyl 6-(piperidin-1-ylmethyl)nicotinate

Product 2

HCID 222AmmoniaYield 3%HCID 11522780(4-Isopropyl-piperazin-1-yl)-(6-piperidin-1-ylmethyl-pyridin-3-yl)-methanoneYield 140.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 6-piperidin-1-ylmethyl-nicotinic acid methyl ester (0.300 g, 1.28 mmol), and MgBr2.OEt2 (0.900 g, 3.84 mmol) in THF (15 mL) was stirred for 15 min. A solution of 1-isopropyl-piperazine (0.325 g, 2.56 mmol) in THF (2 mL) was then added to the reaction drop-wise and the mixture was heated at reflux for 48 h. The reaction mixture was cooled to rt, concentrated, treated with 1 N aq. NaHCO3 (50 mL), and extracted with ethyl acetate (3×50 mL). The organic layers were combined, dried (Na2SO4), and concentrated. Chromatography of the residue (SiO2; 3-6% 2 M NH3 in MeOH/DCM) gave the title compound as an oil (0.297 g, 70%). MS (ESI): exact mass calcd. for C19H30N4O, 330.2; m/z found, 331.2 [M+H]+. 1H NMR (400 MHz, CDCl3): 8.55 (d, J=2.2, 1H), 7.87 (dd, J=7.8, 2.0, 1H), 7.62 (d, J=7.6, 1H), 3.78 (br s, 2H), 3.67 (s, 2H), 3.48 (br s, 2H), 2.77-2.73 (m, 1H), 2.65-2.48 (m, 8H), 1.65-1.59 (m, 4H), 1.49-1.48 (m, 2H), 1.09 (d, J=6.6, 6H).

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux for 48 h
  3. concentrationconcentrated
  4. additiontreated with 1 N aq. NaHCO3 (50 mL)
  5. extractionextracted with ethyl acetate (3×50 mL)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-20e31187433e46aebff1d7b7dceb68c5
Source dataset
uspto-grants-2008_09
Patent number
US07423147B2

Linked notes

Loading…