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Water → Tert-butyl 4-[2'-(2-{[(cyanomethyl)amino]carbonyl}-4-methylpentyl)[1,1'-biphenyl]-4-yl]-1-piperazinecarboxylate

HRID 1744073
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HRID 1744073 반응식
Br[C:2]1[CH:19]=[CH:18][CH:17]=[CH:16][C:3]=1[CH2:4][CH:5]([CH2:12][CH:13]([CH3:15])[CH3:14])[C:6]([NH:8][CH2:9][C:10]#[N:11])=[O:7].[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:10]([CH2:9][NH:8][C:6]([CH:5]([CH2:12][CH:13]([CH3:15])[CH3:14])[CH2:4][C:3]1[CH:16]=[CH:17][CH:18]=[CH:19][C:2]=1[C:36]1[CH:35]=[CH:34][C:33]([N:30]2[CH2:29][CH2:28][N:27]([C:25]([O:24][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:26])[CH2:32][CH2:31]2)=[CH:38][CH:37]=1)=[O:7])#[N:11]
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참가 물질

7

반응물 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 52330144-(4-BOC-Piperazino)phenylboronic acidHCID 222361892-(2-bromobenzyl)-N-(cyanomethyl)-4-methylpentanamide

생성물 1

HCID 22235962Tert-butyl 4-[2'-(2-{[(cyanomethyl)amino]carbonyl}-4-methylpentyl)[1,1'-biphenyl]-4-yl]-1-piperazinecarboxylate

시약·촉매·용매 2

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

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온도
90 °C

실험 절차

To 2-(2-bromobenzyl)-N-(cyanomethyl)-4-methylpentanamide (260 mg, 0.805 mmol) and 4-[4-(tert-butoxycarbonyl)-1-piperazinyl]phenylboronic acid (275 mg, 0.886 mmol) in DMF (10 mL) under dry nitrogen was added aqueous sodium carbonate (2 M, 1.2 mL, 2.42 mmol) followed by the catalyst PdCl2(dppf) (25 mg, 0.025 mmol). The reaction was heated to 90° C. for 0.5 hours and more PdCl2(dppf) (25 mg, 0.025 mmol) was added and the reaction mixture was heated for another 4 hours. 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, 35/65) to afford tert-butyl 4-[2′-(2-{[(cyanomethyl)amino]carbonyl}-4-methylpentyl)[1,1 ′-biphenyl]-4-yl]-1-piperazinecarboxylate.

후처리

  1. temperaturethe reaction mixture was heated for another 4 hours
  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, 35/65)

출처 및 근거

ORD 기록
ord-7a6f68e372b1441dbc2a21c8b365f9e8
출처 데이터셋
uspto-grants-2006_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07012075B2

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