Ethanol → N-[4-(3'-cyano-biphenyl-4-yl)-1-cyclopropylmethyl-piperidin-4-ylmethyl]-2-(3,5-difluoro-phenyl)-acetamide

HRID 2180171노트

반응식

HRID 2180171 반응식
[CH:1]1([CH2:4][N:5]2[CH2:10][CH2:9][C:8]([CH2:18][NH:19][C:20](=[O:30])[CH2:21][C:22]3[CH:27]=[C:26]([F:28])[CH:25]=[C:24]([F:29])[CH:23]=3)([C:11]3[CH:16]=[CH:15][C:14](I)=[CH:13][CH:12]=3)[CH2:7][CH2:6]2)[CH2:3][CH2:2]1.[C:31]([C:33]1[CH:34]=[C:35](B(O)O)[CH:36]=[CH:37][CH:38]=1)#[N:32].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>[C:31]([C:33]1[CH:38]=[C:37]([C:14]2[CH:15]=[CH:16][C:11]([C:8]3([CH2:18][NH:19][C:20](=[O:30])[CH2:21][C:22]4[CH:27]=[C:26]([F:28])[CH:25]=[C:24]([F:29])[CH:23]=4)[CH2:9][CH2:10][N:5]([CH2:4][CH:1]4[CH2:3][CH2:2]4)[CH2:6][CH2:7]3)=[CH:12][CH:13]=2)[CH:36]=[CH:35][CH:34]=1)#[N:32]

참가 물질

8

반응물 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 27343253-Cyanophenylboronic acidHCID 68533825N-[1-cyclopropylmethyl-4-(4-iodo-phenyl)-piperidin-4-ylmethyl]-2-(3,5-difluoro-phenyl)-acetamide

생성물 1

HCID 22490375N-[4-(3'-cyano-biphenyl-4-yl)-1-cyclopropylmethyl-piperidin-4-ylmethyl]-2-(3,5-difluoro-phenyl)-acetamide수율 60%

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 1140Toluene용매

실험 절차

To a flask containing 1 N-[1-cyclopropylmethyl-4-(4-iodo-phenyl)-piperidin-4-ylmethyl]-2-(3,5-difluoro-phenyl)-acetamide (0.040 g, 0.76 mmol) was added Pd(PPh3)4 (0.01 g, 0.008 mmol, 10 mol %), 3-cyanophenylboronic acid (0.020 g, 0.12 mmol, 1.5 eq.) and Na2CO3 (0.106 g, 1 mmol). The mixture was suspended in toluene (1.5 mL), EtOH (0.75 mL) and H2O (0.5 mL) and heated to 80° C. for 18 h. The reaction mixture was cooled to room temperature and partitioned between EtOAc (5 mL) and saturated Na2CO3 (5 mL). The organic layer was washed with saturated Na2CO3 (3×5 mL), saturated brine (2×5 mL), dried over anhydrous sodium sulfate, filtered and concentrated to give a brown solid which was purified by HPLC to give the title compound N-[4-(3′-cyano-biphenyl-4-yl)-1-cyclopropylmethyl-piperidin-4-ylmethyl]-2-(3,5-difluoro-phenyl)-acetamide (0.036 g, 0.072 mmol, 10%). MS(ESI): 500.3/501.3 (M+1).

후처리

  1. custompartitioned between EtOAc (5 mL) and saturated Na2CO3 (5 mL)
  2. washThe organic layer was washed with saturated Na2CO3 (3×5 mL), saturated brine (2×5 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a brown solid which
  7. customwas purified by HPLC

출처 및 근거

ORD 기록
ord-e0228cd9398d475a8484708452270de5
출처 데이터셋
uspto-grants-2005_05
특허 번호
US06887889B2

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