Diisopropylethylamine → 4-[3-(2-Chloro-pyrimidin-4-yl)-benzyl]-2-(R)-methyl-piperazine-1-carboxylic acid tert-butyl ester

HRID 14926

반응식

HRID 14926 반응식
[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[C:10]([CH:17]=[CH:18][CH:19]=2)[CH2:11]OS(C)(=O)=O)[CH:5]=[CH:4][N:3]=1.[C:20]([O:24][C:25]([N:27]1[CH2:32][CH2:31][NH:30][CH2:29][C@H:28]1[CH3:33])=[O:26])([CH3:23])([CH3:22])[CH3:21].C(N(C(C)C)CC)(C)C>COCCOC>[C:20]([O:24][C:25]([N:27]1[CH2:32][CH2:31][N:30]([CH2:11][C:10]2[CH:17]=[CH:18][CH:19]=[C:8]([C:6]3[CH:5]=[CH:4][N:3]=[C:2]([Cl:1])[N:7]=3)[CH:9]=2)[CH2:29][C@H:28]1[CH3:33])=[O:26])([CH3:23])([CH3:21])[CH3:22]

참가 물질

5

반응물 3

HCID 81531DiisopropylethylamineHCID 10262201tert-Butyl (2R)-2-methylpiperazine-1-carboxylate2회HCID 86603313Methanesulfonic acid 3-(2-chloro-pyrimidin-4-yl)-benzyl ester2회

생성물 1

HCID 866033144-[3-(2-Chloro-pyrimidin-4-yl)-benzyl]-2-(R)-methyl-piperazine-1-carboxylic acid tert-butyl ester수율 53%

시약·촉매·용매 1

HCID 80711,2-Dimethoxyethane용매

실험 절차

Intermediate 125 Methanesulfonic acid 3-(2-chloro-pyrimidin-4-yl)-benzyl ester (0.70 g) and Intermediate 127 2-(R)-Methyl-piperazine-1-carboxylic acid tert-butyl ester (0.61 g) with diisopropylethylamine (0.70 mL) in ethylene glycol dimethyl ether (20 mL) was refluxed for 3 hours, cooled to room temperature, evaporated under reduced pressure and the residue was dissolved in dichloromethane, washed with water (3×), brine, dried over dried over Na2SO4, chromatographed on silica gel (dichloromethane:methanol=98:2) to give 0.50 g of oily product with yield 53%. LC-MS showed the product had the expected M+H+ of 403. 1H NMR (Varian 300 MHz, CDCl3, shifts relative to the solvent peak at 7.24 ppm) δ 8.6 (s, 1H) 8.0 (s, 1H) 7.9 (d, 1H) 7.6 (d, 1H) 7.5 (m, 2H) 4.2 (S, 1 h) 3.8 (d, 1H) 3.4 (m, 2H) 3.0 (m, 1H) 2.7 (d, 1H), 2.6 (d, 1H) 2.1 (m, 2H) 1.4 (s, 9H) 1.2 (d, 3H).

후처리

  1. customevaporated under reduced pressure
  2. dissolutionthe residue was dissolved in dichloromethane
  3. washwashed with water (3×), brine
  4. customdried
  5. dry with materialover dried over Na2SO4
  6. customchromatographed on silica gel (dichloromethane:methanol=98:2)

출처 및 근거

ORD 기록
ord-f0c60d0c77b2435c963747fb4f3fe129
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07732444B2

연결된 노트

불러오는 중…