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

HRID 551577

반응식

HRID 551577 반응식
[CH:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]([C:12]2[CH:13]=[N:14][C:15]([CH2:18][N:19]3[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]3)=[CH:16][CH:17]=2)=[O:11])[CH2:6][CH2:5]1)([CH3:3])[CH3:2].COC(=O)C1C=CC(CN2CCCCC2)=NC=1.[Mg+2].[Br-].[Br-].O(CC)CC.C(N1CCNCC1)(C)C>C1COCC1>[NH3:4].[CH:1]([N:4]1[CH2:5][CH2:6][N:7]([C:10]([C:12]2[CH:13]=[N:14][C:15]([CH2:18][N:19]3[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24]3)=[CH:16][CH:17]=2)=[O:11])[CH2:8][CH2:9]1)([CH3:3])[CH3:2]

참가 물질

8

반응물 5

HCID 3283Diethyl EtherHCID 780131-IsopropylpiperazineHCID 82241Magnesium BromideHCID 11522780(4-Isopropyl-piperazin-1-yl)-(6-piperidin-1-ylmethyl-pyridin-3-yl)-methanoneHCID 44515770Methyl 6-(piperidin-1-ylmethyl)nicotinate

생성물 2

HCID 222Ammonia수율 3%HCID 11522780(4-Isopropyl-piperazin-1-yl)-(6-piperidin-1-ylmethyl-pyridin-3-yl)-methanone수율 70%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

(4-Isopropyl-piperazin-1-yl)-(6-piperidin-1-ylmethyl-pyridin-3-yl)-methanone. 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).

후처리

  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

출처 및 근거

ORD 기록
ord-f9382c9d72f0458aa7a95e165314612d
출처 데이터셋
uspto-grants-2011_05
특허 번호
US07947718B2

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