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

HRID 470921
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HRID 470921 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(B(O)O)[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1>C(Cl)Cl.CC([O-])=O.CC([O-])=O.[Cu+2]>[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][N:23]([C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)[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]
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참가 물질

6

반응물 3

HCID 1049PyridineHCID 66827Phenylboronic 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 86692194Methyl 2-tert-butoxy-2-(4-(4-fluorophenyl)-2-isopropyl-8,8-dimethyl-6-phenyl-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)acetate

시약·촉매·용매 2

HCID 8895
Cupric acetate
촉매
HCID 6344Dichloromethane용매

실험 절차

A mixture of Cu(OAc)2 (8.21 mg, 0.045 mmol) and pyridine (3.66 μl, 0.045 mmol) in CH2Cl2 (0.5 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) (10 mg, 0.023 mmol), phenylboronic acid (5.51 mg, 0.045 mmol) and 17 mg molecular sieves. The resulting mixture was stirred at room temperature open to air for 17 h. The mixture was adsorbed directly onto silica gel and purified by flash chromatography (Biotage; 0%-50% EtOAc/hexane). 1H NMR (500 MHz, CDCl3) δ ppm 7.38 (ddd, J=8.4, 5.8, 2.3 Hz, 1H), 7.27-7.16 (m, 5H), 6.87-6.73 (m, 3H), 4.86 (s, 1H), 3.94 (d, J=15.6 Hz, 1H), 3.73 (s, 3H), 3.69 (d, J=15.6 Hz, 1H), 3.55 (dt, J=13.0, 6.4 Hz, 1H), 3.44-3.34 (m, 1H), 3.28 (d, J=12.5Hz, 1H), 1.49 (d, J=3.7 Hz, 6H), 1.33 (d, J=6.1 Hz, 3H), 1.17 (d, J=6.7 Hz, 3H), 1.01 (s, 9H). 19F NMR (500 MHz, CDCl3) δ ppm −113.64. LCMS (M+H) calcd for C32H40FN2O3: 519.30. found: 519.45.

후처리

  1. stirringThe resulting mixture was stirred at room temperature open to air for 17 h
  2. custompurified by flash chromatography (Biotage; 0%-50% EtOAc/hexane)

출처 및 근거

ORD 기록
ord-401d553b13864251921153957528ffaa
출처 데이터셋
uspto-grants-2014_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08629276B2

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