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Water → N1-(cyanomethyl)-N2-(4-{4-[4-(tert-butoxycarbonyl)piperazin-1-yl]phenyl}-1-methyl-1H-pyrazol-3-yl)leucinamide

HRID 1744117
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HRID 1744117 반응식
Br[C:2]1[C:3]([NH:8][C@H:9]([C:14]([NH:16][CH2:17][C:18]#[N:19])=[O:15])[CH2:10][CH:11]([CH3:13])[CH3:12])=[N:4][N:5]([CH3:7])[CH:6]=1.[C:20]([O:24][C:25]([N:27]1[CH2:32][CH2:31][N:30]([C:33]2[CH:38]=[CH:37][C:36](B(O)O)=[CH:35][CH:34]=2)[CH2:29][CH2:28]1)=[O:26])([CH3:23])([CH3:22])[CH3:21].C(=O)([O-])[O-].[Na+].[Na+].O>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:18]([CH2:17][NH:16][C:14](=[O:15])[C@H:9]([CH2:10][CH:11]([CH3:13])[CH3:12])[NH:8][C:3]1[C:2]([C:36]2[CH:35]=[CH:34][C:33]([N:30]3[CH2:29][CH2:28][N:27]([C:25]([O:24][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:26])[CH2:32][CH2:31]3)=[CH:38][CH:37]=2)=[CH:6][N:5]([CH3:7])[N:4]=1)#[N:19]
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참가 물질

7

반응물 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 52330144-(4-BOC-Piperazino)phenylboronic acidHCID 86594568N2-(4-bromo-1-methyl-1H-pyrazol-3-yl)-N1-(cyanomethyl)leucinamide

생성물 1

HCID 86594569N1-(cyanomethyl)-N2-(4-{4-[4-(tert-butoxycarbonyl)piperazin-1-yl]phenyl}-1-methyl-1H-pyrazol-3-yl)leucinamide

시약·촉매·용매 2

HCID 44119782
Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)
촉매
3회
HCID 6228Dimethylformamide용매

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온도
90 °C

실험 절차

To N2-(4-bromo-1-methyl-1H-pyrazol-3-yl)-N1-(cyanomethyl)leucinamide (250 mg, 0.762 mmol), and 4-[4-(tert-butoxycarbonyl)-1-piperazinyl]phenylboronic acid (350 mg, 1.14 mmol, prepared as described in Example 1) in DMF (8 mL) under dry nitrogen was added aqueous sodium carbonate (2.0 M, 0.9 mL, 1.7 mmol) followed by the catalyst PdCl2(dppf) (20 mg, 0.022 mmol). The reaction was heated to 90° C. for 0.5 hours and an additional aliquot of PdCl2(dppf) (20 mg, 0.022 mmol) was added and the reaction mixture heated for 1½ hour during which time an additional aliquot of PdCl2(dppf) (20 mg, 0.022 mmol) was added. Water was added and the product extracted with ether (2×), dried over Na2SO4, concentrated in vacuo and purified by flash chromatography over silica gel (EtOAc/Hex, 6/4 then 8/2) to afford N1-(cyanomethyl)-N2-(4-{4-[4-(tert-butoxycarbonyl)piperazin-1-yl]phenyl}-1-methyl-1H-pyrazol-3-yl)leucinamide.

후처리

  1. additionwas added
  2. extractionthe product extracted with ether (2×)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. custompurified by flash chromatography over silica gel (EtOAc/Hex, 6/4

출처 및 근거

ORD 기록
ord-0f56e6c90f094bec98f54c9a9836830e
출처 데이터셋
uspto-grants-2006_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07012075B2

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