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Diisopropylethylamine → Isopropyl 2-(5-bromo-4-(4-cyano-4-methylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-oxoacetate

HRID 718407
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HRID 718407 반응식
CC[N:3]([CH:7]([CH3:9])C)[CH:4]([CH3:6])C.[Br:10][C:11]1[C:12](Cl)=[C:13]([C:19](=[O:26])[C:20]([O:22][CH:23]([CH3:25])[CH3:24])=[O:21])[C:14]([CH3:18])=[N:15][C:16]=1[CH3:17]>CC#N.CCOCC>[Br:10][C:11]1[C:12]([N:3]2[CH2:4][CH2:6][C:13]([C:14]#[N:15])([CH3:12])[CH2:9][CH2:7]2)=[C:13]([C:19](=[O:26])[C:20]([O:22][CH:23]([CH3:25])[CH3:24])=[O:21])[C:14]([CH3:18])=[N:15][C:16]=1[CH3:17]
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참가 물질

5

반응물 2

HCID 81531DiisopropylethylamineHCID 118307804Isopropyl 2-(5-bromo-4-chloro-2,6-dimethylpyridin-3-yl)-2-oxoacetate

생성물 1

HCID 118307723Isopropyl 2-(5-bromo-4-(4-cyano-4-methylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-oxoacetate수율 76.1%

시약·촉매·용매 2

HCID 3283Diethyl Ether용매HCID 6342Acetonitrile용매

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온도
80 °C

실험 절차

To a solution of 4-methylpiperidine-4-carbonitrile, HCl (1.0 g, 6.22 mmol) and DIEA (4.4 mL, 24.9 mmol) in anhydrous CH3CN (30 mL) was added isopropyl 2-(5-bromo-4-chloro-2,6-dimethylpyridin-3-yl)-2-oxoacetate (2.1 g, 6.22 mmol) at rt. The resulting mixture was placed in a pre-heated oil bath (80° C.) and stirred for 72 h; cooled, diluted with ether, washed with water, brine, and dried (MgSO4). The crude product was charged (DCM) to a 80 g ISCO silica gel cartridge and gradient eluted (5-35% EtOAc/hexanes) using an Isolera chromatography station to give isopropyl 2-(5-bromo-4-(4-cyano-4-methylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-oxoacetate 1.0 g (38%). 1H NMR (500 MHz, DMSO-d6) δ 5.08-5.03 (m, 1H), 3.54-3.40 (m, 4H), 2.61 (s, 3H), 2.30 (s, 3H), 1.92 (d, J=12.4 Hz, 2H), (2H missing), 1.35 (s, 3H), 1.28 (d, J=5.9 Hz, 6H). UPLC (M+H)=424.3.

후처리

  1. customThe resulting mixture was placed in a pre-heated oil bath
  2. temperaturecooled
  3. washwashed with water, brine
  4. dry with materialdried (MgSO4)
  5. additionThe crude product was charged (DCM) to a 80 g ISCO silica gel cartridge and gradient
  6. washeluted (5-35% EtOAc/hexanes)

출처 및 근거

ORD 기록
ord-283472ba5c534e65b62b31fb96c84519
출처 데이터셋
uspto-grants-2015_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09193720B2

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