2-Methoxyphenylboronic acid → (3-{[2-(2'-Methoxy-biphenyl-2-ylamino)-ethylamino]-methyl}-phenyl)-piperidin-1-yl-methanone

HRID 606666노트

반응식

HRID 606666 반응식
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][CH2:9][CH2:10][NH:11][CH2:12][C:13]1[CH:14]=[C:15]([C:19]([N:21]2[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]2)=[O:20])[CH:16]=[CH:17][CH:18]=1.[CH3:27][O:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1B(O)O>C([O-])([O-])=O.[Na+].[Na+].CCO.C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:27][O:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][CH2:9][CH2:10][NH:11][CH2:12][C:13]1[CH:14]=[C:15]([C:19]([N:21]2[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]2)=[O:20])[CH:16]=[CH:17][CH:18]=1

참가 물질

5

반응물 2

HCID 27339582-Methoxyphenylboronic acidHCID 58975554(3-{[2-(2-Bromo-phenylamino)-ethylamino]-methyl}-phenyl)-piperidin-1-yl-methanone

생성물 1

HCID 58975557(3-{[2-(2'-Methoxy-biphenyl-2-ylamino)-ethylamino]-methyl}-phenyl)-piperidin-1-yl-methanone수율 31.6%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 18778779HCID 18778779, 화합물용매

실험 절차

To a solution of (3-{[2-(2-bromo-phenylamino)-ethylamino]-methyl}-phenyl)piperidin-1-yl-methanone (Example 17; 0.051 g, 0.12 mmol) and 2-methoxybenzeneboronic acid (0.037 g, 0.25 mmol) in 2 M Na2CO3/EtOH/toluene (1:1:4, 6 mL) was added Pd(PPh3)4 (0.014 g, 0.012 mmol), and the resulting solution was stirred at reflux for 16 h. The solution was partitioned with EtOAc (20 mL) and satd aqueous NaHCO3 (20 mL), and the aqueous layer was back-extracted with EtOAc (3×30 mL). The combined organic layers were washed with brine, dried (MgSO4), filtered, and concentrated under reduced pressure. The crude residue was purified by preparative TLC (10% CH3OH/CH2Cl2) to provide a tan oil (0.0168 g, 28%). MS (ESI): mass calculated for C28H33N3O2, 443.26; m/z found, 444.2 [M+H]+, 466.2 [M+Na]+. 1H NMR (400 MHz, CDCl3): 7.38-7.22 (m, 7H), 7.08-6.97 (m, 3H), 6.78-6.72 (br s, 2H), 4.15 (br s, 1H), 3.69-3.76 (br m, 4H), 3.68 (s, 3H), 3.29-3.24 (br m, 4H), 2.86-2.76 (m, 2H), 1.75-1.49 (br m, 8H). 13C NMR (100 MHz, CDCl3): 170.2, 156.8, 145.8, 140.4, 136.5, 131.9, 130.7, 129.0, 128.9, 128.6, 128.4, 128.0, 126.4, 125.3, 124.9, 121.1, 116.8, 111.2, 110.5, 55.6, 53.2, 48.7, 47.8, 43.5, 43.6, 26.5, 25.6, 24.5.

후처리

  1. temperatureat reflux for 16 h
  2. customThe solution was partitioned with EtOAc (20 mL)
  3. extractionthe aqueous layer was back-extracted with EtOAc (3×30 mL)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude residue was purified by preparative TLC (10% CH3OH/CH2Cl2)

출처 및 근거

ORD 기록
ord-8156bfc67ba54be9819311081cc26b83
출처 데이터셋
uspto-grants-2011_03
특허 번호
US07915420B2

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