Toluene → N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(4-(2-methylpyridin-4-yl)-3-(trifluoromethyl)phenyl)acetamide

HRID 1036234노트

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HRID 1036234 반응식
[C:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:11]=[CH:12][C:13]([NH:16][C:17](=[O:30])[CH2:18][C:19]3[CH:24]=[CH:23][C:22](Br)=[C:21]([C:26]([F:29])([F:28])[F:27])[CH:20]=3)=[N:14][CH:15]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[CH3:31][C:32]1[CH:37]=[C:36](B(O)O)[CH:35]=[CH:34][N:33]=1.C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>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.C(O)C>[C:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:11]=[CH:12][C:13]([NH:16][C:17](=[O:30])[CH2:18][C:19]3[CH:24]=[CH:23][C:22]([C:36]4[CH:35]=[CH:34][N:33]=[C:32]([CH3:31])[CH:37]=4)=[C:21]([C:26]([F:29])([F:28])[F:27])[CH:20]=3)=[N:14][CH:15]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2]

참가 물질

7

반응물 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 41926642-Methylpyridine-4-boronic acidHCID 58447760N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(4-bromo-3-(trifluoromethyl)phenyl)acetamide

생성물 1

HCID 58447713N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(4-(2-methylpyridin-4-yl)-3-(trifluoromethyl)phenyl)acetamide

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 702Ethanol용매

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온도
110 °C

실험 절차

To a reaction vessel charged with N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(4-bromo-3-(trifluoromethyl)phenyl)acetamide 192-1 (300 mg, 0.62 mmol), 2-methylpyridin-4-ylboronic acid 172-1 (127 mg, 0.93 mmol) and Pd(PPh3)4 (36 m g, 0.03 mmol) was added toluene (6 mL), ethanol (2 mL) and saturated sodium carbonate (2 mL). The reaction mixture was flushed with nitrogen and heated to 110° C. for 10 hours. After the reaction was cooled down to room temperature, it was partitioned between ethyl acetate and saturated NaHCO3 and the organic phase was washed with brine and dried over Na2SO4. The solvent was removed by rotary evaporation and the residue was purified by reverse phase HPLC to give N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(4-(2-methylpyridin-4-yl)-3-(trifluoromethyl)phenyl)acetamide 172. MS m/z 498.2 (M+1). 1H NMR 400 MHz (DMSO-d6) δ10.67 (s, 1H), 8.66 (d, 1H), 8.05 (m, 1H), 7.94 (m, 2H), 7.75 (d, 1H), 7.52 (s, 1H), 7.45 (m, 3H), 3.88 (s, 2H), 3.58 (b, 4H), 3.14 (b, 2H), 3.09 (b, 2H), 2.61 (s, 3H), 2.05 (s, 3H).

후처리

  1. customThe reaction mixture was flushed with nitrogen
  2. temperatureAfter the reaction was cooled down to room temperature
  3. customit was partitioned between ethyl acetate and saturated NaHCO3
  4. washthe organic phase was washed with brine
  5. dry with materialdried over Na2SO4
  6. customThe solvent was removed by rotary evaporation
  7. customthe residue was purified by reverse phase HPLC

출처 및 근거

ORD 기록
ord-2a485fca9b6d40ed85813690412e9a2b
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08546396B2

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