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Diisopropylethylamine → 5-(5-(1-Acetyl-piperidin-4-yl)-2-{[4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carbonyl]-amino}-phenyl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester

HRID 1445238
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HRID 1445238 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:13][C:12]([C:14]2[CH:19]=[C:18]([CH:20]3[CH2:25][CH2:24][N:23]([C:26](=[O:28])[CH3:27])[CH2:22][CH2:21]3)[CH:17]=[CH:16][C:15]=2[NH2:29])=[CH:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[C:54]([C:56]1[N:57]=[C:58]([C:69](O)=[O:70])[N:59]([CH2:61][O:62][CH2:63][CH2:64][Si:65]([CH3:68])([CH3:67])[CH3:66])[CH:60]=1)#[N:55].[K+].C(C1N=C(C([O-])=O)N(COCC[Si](C)(C)C)C=1)#N.CCN(C(C)C)C(C)C>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:13][C:12]([C:14]2[CH:19]=[C:18]([CH:20]3[CH2:21][CH2:22][N:23]([C:26](=[O:28])[CH3:27])[CH2:24][CH2:25]3)[CH:17]=[CH:16][C:15]=2[NH:29][C:69]([C:58]2[N:59]([CH2:61][O:62][CH2:63][CH2:64][Si:65]([CH3:68])([CH3:67])[CH3:66])[CH:60]=[C:56]([C:54]#[N:55])[N:57]=2)=[O:70])=[CH:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
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참가 물질

7

반응물 5

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 591285815-[5-(1-Acetyl-piperidin-4-yl)-2-amino-phenyl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl esterHCID 591285854-Cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole-2-carboxylic acidHCID 67188357potassium 4-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole-2-carboxylate

생성물 1

HCID 591285915-(5-(1-Acetyl-piperidin-4-yl)-2-{[4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carbonyl]-amino}-phenyl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester수율 98%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

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온도
0 °C

실험 절차

A solution of 5-[5-(1-acetyl-piperidin-4-yl)-2-amino-phenyl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (as prepared in the previous step, 0.25 g, 0.63 mmol) in CH2Cl2 was treated with PyBroP (0.44 g, 0.94 mmol) and 4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid, potassium salt (as prepared in Example 3, step (d), 0.21 g, 0.69 mmol). The resulting slurry was cooled to 0° C. and treated with DIEA (0.33 mL, 1.88 mmol). The ice bath was removed and the mixture stirred at room temperature for 18 h. The reaction was diluted with CH2Cl2 and washed with saturated aqueous NaHCO3. The organic layer was dried over MgSO4 and concentrated in vacuo. Silica gel chromatography (25-45% EtOAc in hexanes then 100% EtOAc) afforded the title compound (399 mg, 98%) as a white solid. LC-MS (ESI, m/z): Calcd. for C34H48N6O5Si 649.4 (M+H), found 649.9.

후처리

  1. customThe ice bath was removed
  2. additionThe reaction was diluted with CH2Cl2
  3. washwashed with saturated aqueous NaHCO3
  4. dry with materialThe organic layer was dried over MgSO4
  5. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-7f885dac9f57496499337ab74ad1cb82
출처 데이터셋
uspto-grants-2010_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07662837B2

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