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Acetic Anhydride → 2-[6-Acetyl-4-(4-fluorophenyl)-2-isopropyl-8,8-dimethyl-5,7-dihydro-1,6-naphthyridin-3-yl]-2-tert-butoxy-acetic acid

HRID 470931
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HRID 470931 반응식
[C:1]([O:5][CH:6]([C:10]1[C:11]([CH:29]([CH3:31])[CH3:30])=[N:12][C:13]2[C:14]([CH3:28])([CH3:27])[CH2:15][NH:16][CH2:17][C:18]=2[C:19]=1[C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=1)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:3])[CH3:2].CCN(CC)CC.[CH3:39][C:40](OC(C)=O)=[O:41]>C(Cl)Cl>[C:40]([N:16]1[CH2:15][C:14]([CH3:28])([CH3:27])[C:13]2[N:12]=[C:11]([CH:29]([CH3:31])[CH3:30])[C:10]([CH:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[C:7]([OH:9])=[O:8])=[C:19]([C:20]3[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=3)[C:18]=2[CH2:17]1)(=[O:41])[CH3:39]
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참가 물질

5

반응물 3

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 717115302-Tert-butoxy-2-(4-(4-fluorophenyl)-2-isopropyl-8,8-dimethyl-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)acetic acid

생성물 1

HCID 717115312-[6-Acetyl-4-(4-fluorophenyl)-2-isopropyl-8,8-dimethyl-5,7-dihydro-1,6-naphthyridin-3-yl]-2-tert-butoxy-acetic acid수율 83.5%

시약·촉매·용매 1

HCID 6344
Dichloromethane
용매

실험 절차

To a stirred solution of 2-tert-butoxy-2-(4-(4-fluorophenyl)-2-isopropyl-8,8-dimethyl-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)acetic acid (example 1)(0.012 g, 0.028 mmol) and Et3N (0.139 ml, 1 mmol) in CH2Cl2 (5 mL) was added Ac2O (0.026 ml, 0.280 mmol) at room temperature. After 3 h, the reaction mixture concentrated and purified by preparative-HPLC (MeCN/H2O/NH4OAc) to afford 2-(6-acetyl-4-(4-fluorophenyl)-2-isopropyl-8,8-dimethyl-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)-2-tert-butoxyacetic acid (0.011 g, 76% yield) as white powder and mixture of rotomers. 1H NMR (500 MHz, CDCl3) δ ppm 7.41-7.54 (1H, m), 7.11-7.23 (3H, m), 4.91 (1H, br. s.), 4.49 (0.7H, d, J=17.4 Hz), 4.28 (0.3H, d, J=16.5Hz), 4.08 (0.7H, d, J=17.7 Hz), 3.93 (0.3H, d, J=16.8 Hz), 3.39-3.52 (2H, m), 3.15-3.27 (1H, m), 2.15 (2H, s), 1.95 (1H, s), 1.27-1.39 (9H, m), 1.15 (3H, d, J=5.5Hz), 0.90 (3H, s), 1.00 (6H, s). LCMS (M+H) calcd for C27H36FN2O4: 471.27. found: 471.3.

후처리

  1. concentrationthe reaction mixture concentrated
  2. custompurified by preparative-HPLC (MeCN/H2O/NH4OAc)
  3. customto afford

출처 및 근거

ORD 기록
ord-b797a82a23924b528de1ed1c97a8ce4b
출처 데이터셋
uspto-grants-2014_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08629276B2

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