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Pyridine → Methyl 2-(6-([1,1'-biphenyl]-4-yl)-4-(4-fluorophenyl)-2-isopropyl-8,8-dimethyl-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)-2-(tert-butoxy)acetate

HRID 470924
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HRID 470924 반응식
N1C=CC=CC=1.[C:7]([O:11][CH:12]([C:17]1[C:18]([CH:36]([CH3:38])[CH3:37])=[N:19][C:20]2[C:21]([CH3:35])([CH3:34])[CH2:22][NH:23][CH2:24][C:25]=2[C:26]=1[C:27]1[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=1)[C:13]([O:15][CH3:16])=[O:14])([CH3:10])([CH3:9])[CH3:8].[C:39]1([C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)[CH:44]=[CH:43][C:42](B(O)O)=[CH:41][CH:40]=1>C(Cl)Cl.CC([O-])=O.CC([O-])=O.[Cu+2]>[C:39]1([C:48]2[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=2)[CH:44]=[CH:43][C:42]([N:23]2[CH2:22][C:21]([CH3:35])([CH3:34])[C:20]3[N:19]=[C:18]([CH:36]([CH3:38])[CH3:37])[C:17]([CH:12]([O:11][C:7]([CH3:10])([CH3:9])[CH3:8])[C:13]([O:15][CH3:16])=[O:14])=[C:26]([C:27]4[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=4)[C:25]=3[CH2:24]2)=[CH:41][CH:40]=1
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참가 물질

6

반응물 3

HCID 1049PyridineHCID 1512531,1'-Biphenyl-4-yl-boronic acidHCID 86692192Methyl 2-tert-butoxy-2-(4-(4-fluorophenyl)-2-isopropyl-8,8-dimethyl-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)acetate2회

생성물 1

HCID 86692197Methyl 2-(6-([1,1'-biphenyl]-4-yl)-4-(4-fluorophenyl)-2-isopropyl-8,8-dimethyl-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)-2-(tert-butoxy)acetate수율 84.8%

시약·촉매·용매 2

HCID 8895Cupric acetate촉매HCID 6344Dichloromethane용매

실험 절차

A mixture of Cu(OAc)2 (16.42 mg, 0.090 mmol) and pyridine (7 μl, 0.09 mmol) in CH2Cl2 (1 mL) was stirred for 5 min. Added to this were methyl 2-(tert-butoxy)-2-(4-(4-fluorophenyl)-2-isopropyl-8,8-dimethyl-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)acetate (intermediate 5) (20 mg, 0.045 mmol), 4-biphenylboronic acid (17.90 mg, 0.09 mmol) and 34 mg molecular sieves. After stirring uncovered for 18 h, the mixture was adsorbed directly onto silica gel and was purified by flash column chromatography (Biotage; 0%-50% EtOAc/hexane) to give methyl 2-(6-([1,1′-biphenyl]-4-yl)-4-(4-fluorophenyl)-2-isopropyl-8,8-dimethyl-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)-2-(tert-butoxy)acetate (22.7 mg, 84% yield) as a colorless oil. LCMS (M+H) calcd for C38H44FN2O3: 595.33. found: 595.4. 19F NMR (500 MHz, Methanol d4) δ ppm: −113.055.

후처리

  1. stirringAfter stirring
  2. waituncovered for 18 h
  3. customwas purified by flash column chromatography (Biotage; 0%-50% EtOAc/hexane)

출처 및 근거

ORD 기록
ord-a180de50cf324295a3908a2348d282ae
출처 데이터셋
uspto-grants-2014_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08629276B2

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