Ethanol → 4-(3'-Cyano-biphenyl-4-yl)-1-methyl-piperidine-4-carboxylic acid (3,5-dichloro-phenyl)-amide

HRID 2180193노트

반응식

HRID 2180193 반응식
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]([C:12]2([C:19]3[CH:24]=[CH:23][C:22](I)=[CH:21][CH:20]=3)[CH2:17][CH2:16][N:15]([CH3:18])[CH2:14][CH2:13]2)=[O:11])[CH:5]=[C:6]([Cl:8])[CH:7]=1.[C:26]([C:28]1[CH:29]=[C:30](B(O)O)[CH:31]=[CH:32][CH:33]=1)#[N:27].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.O>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]([C:12]2([C:19]3[CH:24]=[CH:23][C:22]([C:32]4[CH:31]=[CH:30][CH:29]=[C:28]([C:26]#[N:27])[CH:33]=4)=[CH:21][CH:20]=3)[CH2:17][CH2:16][N:15]([CH3:18])[CH2:14][CH2:13]2)=[O:11])[CH:5]=[C:6]([Cl:8])[CH:7]=1

참가 물질

8

반응물 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 27343253-Cyanophenylboronic acidHCID 865871764-(4-Iodo-phenyl)-1-methyl-piperidine-4-carboxylic acid (3,5-dichloro-phenyl)-amide

생성물 1

HCID 207794484-(3'-Cyano-biphenyl-4-yl)-1-methyl-piperidine-4-carboxylic acid (3,5-dichloro-phenyl)-amide수율 400%

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 1140Toluene용매

실험 절차

To a flask containing 4-(4-iodo-phenyl)-1-methyl-piperidine-4-carboxylic acid (3,5-dichloro-phenyl)-amide (175 mg, 0.35 mmol) was added Pd(PPh3)4 (13 mg, 0.035 mmol, 10 mol %), 3-cyanophenylboronic acid (78 mg, 0.53 mmol, 1.5 eq.) and Na2CO3 (0.53 g, 5 mmol). The mixture was suspended in toluene (5 mL), EtOH (2.5 mL) and H2O (2.5 mL) and heated at 90° C. for 18 h. The reaction mixture was cooled to room temperature and partitioned between EtOAc (10 mL) and saturated Na2CO3 (5 mL). The organic layer was washed with saturated Na2CO3 (3×5 mL), dried over anhydrous Na2SO4, filtered and concentrated by rotary evaporation. The crude product was purified by HPLC to give 4-(3′-cyano-biphenyl-4-yl)-1-methyl-piperidine-4-carboxylic acid (3,5-dichloro-phenyl)-amide as a white solid (0.066 g, 1.4 mmol, 14%). 1H NMR (300 MHz, CDCl3): δ 7.95 (M, 1H), 7.91 (M, 1H), 7.62 to 7.76 (m, 6H), 7.51 (d, 2H), 7.19 (br, 1H), 7.15 (t, 1H), 2.71 (m, 6H), 2.42 (s, 3H), 2.30 (m, 2H). MS (ESI): 464.2/466.2 (M+1).

후처리

  1. custompartitioned between EtOAc (10 mL) and saturated Na2CO3 (5 mL)
  2. washThe organic layer was washed with saturated Na2CO3 (3×5 mL)
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated by rotary evaporation
  6. customThe crude product was purified by HPLC

출처 및 근거

ORD 기록
ord-dbe1549e6daa4a8abfbce86bc4a43ea3
출처 데이터셋
uspto-grants-2005_05
특허 번호
US06887889B2

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