2-Chloro-4-methylquinoline → HCID 67400087, 화합물

HRID 913093

반응식

HRID 913093 반응식
Cl[C:2]1[CH:11]=[C:10]([CH3:12])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH:23]([NH2:26])[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14].O(C(C)(C)C)[K]>C(COC)OC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH:23]([NH:26][C:2]2[CH:11]=[C:10]([CH3:12])[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[N:3]=2)[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:14])[CH3:15]

참가 물질

6

반응물 3

HCID 694492-Chloro-4-methylquinolineHCID 12682914-Amino-1-Boc-piperidineHCID 178418922HCID 178418922, 화합물

생성물 1

HCID 67400087HCID 67400087, 화합물

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 80711,2-Dimethoxyethane용매

반응 조건

온도
90 °C

실험 절차

To a degassed solution of 2-chloro-4-methyl-quinoline (1.00 g, 5.63 mmol, 1.0 equiv; commercially available) and 4-amino-piperidine-1-carboxylic acid tert-butyl ester (1.35 g, 6.76 mmol, 1.2 equiv; commercially available) in dimethoxyethane (15 mL) was added KOtert-Bu (0.88 g, 7.88 mmol, 1.4 equiv), (R)-(−)-1-[(S)-2-(dicyclohexyl-phosphino)-ferrocenyl]ethyl-di-tert-butylphosphine (3.12 mg, 0.0056 mmol, 0.1 mol %; Josiphos ligand [CAS RN 158923-11-6]; commercially available from Strem Chemicals, USA) and palladium(II) acetate (1.26 mg, 0.0056 mmol, 0.1 mol %). The reaction mixture was stirred at 90° C. for 18 h, concentrated by evaporation under reduced pressure and the residue purified by silica column chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of heptane (+1% triethylamine)/ethyl acetate providing 0.54 g (28%) of the title compound. 1H NMR (300 MHz, DMSO): δ 1.31-1.40 (m, 2H), 1.41 (s, 9H), 1.91-1.96 (m, 2H), 2.46 (s, 3H), 2.93-3.01 (m, 2H), 3.86-3.91 (m, 2H), 4.11-4.17 (m, 1H), 6.59 (s, 1H), 6.80 (d, J=7.7 Hz, 1H), 7.13-7.17 (m, 1H), 7.44-7.47 (m, 2H), 7.73 (d, J=7.7 Hz, 1H). 13C NMR (75 MHz, DMSO): δ 18.16, 28.07, 31.57, 42.39, 46.37, 78.51, 112.89, 120.88, 123.12, 123.64, 125.96, 128.69, 143.28, 147.91, 153.91, 155.93. MS (ISP): 342.5 [M+H]+.

후처리

  1. concentrationconcentrated by evaporation under reduced pressure
  2. customthe residue purified by silica column chromatography
  3. washeluting with a gradient of heptane (+1% triethylamine)/ethyl acetate providing 0.54 g (28%) of the title compound

출처 및 근거

ORD 기록
ord-1a0e631b38954c5e8607db380e43d0da
출처 데이터셋
uspto-grants-2011_09
특허 번호
US08026255B2

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