1,2-Dichloroethane → 3-[(1-Benzyl-5-hydroxy-2-oxo-3-phenyl-8-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-2,2-dimethyl-propionic acid ethyl ester

HRID 920025노트

반응식

HRID 920025 반응식
[CH2:1]([N:8]1[C:17]2[C:12](=[C:13]([OH:27])[C:14]([C:24]([OH:26])=O)=[N:15][C:16]=2[C:18]2[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=2)[CH:11]=[C:10]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:9]1=[O:34])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.Cl.[CH2:50]([O:52][C:53](=[O:59])[C:54]([CH3:58])([CH3:57])[CH2:55][NH2:56])[CH3:51].CCN(C(C)C)C(C)C>C(Cl)Cl.CCOC(C)=O.[Cl-].[Na+].O.Cl>[CH2:50]([O:52][C:53](=[O:59])[C:54]([CH3:58])([CH3:57])[CH2:55][NH:56][C:24]([C:14]1[C:13]([OH:27])=[C:12]2[C:17](=[C:16]([C:18]3[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=3)[N:15]=1)[N:8]([CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:9](=[O:34])[C:10]([C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1)=[CH:11]2)=[O:26])[CH3:51]

참가 물질

10

반응물 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 18698433Ethyl 3-amino-2,2-dimethylpropanoate hydrochlorideHCID 682974401-Benzyl-5-hydroxy-2-oxo-3-phenyl-8-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid

생성물 1

HCID 682974583-[(1-Benzyl-5-hydroxy-2-oxo-3-phenyl-8-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-2,2-dimethyl-propionic acid ethyl ester수율 44.1%

시약·촉매·용매 4

HCID 313Hydrochloric Acid용매HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매HCID 57417360Sodium chloride; water용매

실험 절차

A mixture of 1-benzyl-5-hydroxy-2-oxo-3-phenyl-8-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid (53 mg, 0.118 mmol) and HOBt (26 mg, 0.189 mmol) was dissolved in CH2Cl2 (3 mL). EDC (41 mg, 0.212 mmol) was added, and the resulting mixture was stirred for 10 min. 3-Amino-2,2-dimethyl-propionic acid ethyl ester HCl salt (34 mg, 0.189 mmol) and Hunig's base (0.075 mL, 0.425 mmol) were added, and the mixture was stirred overnight. The mixture was diluted with EtOAc and brine, and 1 M HCl was added until pH was about 3-4. The aqueous layer was extracted with additional EtOAc, and the organic layers were combined, dried over MgSO4 and concentrated. The crude product was purified by silica gel chromatography (5-60% EtOAc/hexanes+1% AcOH) to give 30 mg of the title compound. MS: (+) m/z 577.40 (M+1).

후처리

  1. stirringthe mixture was stirred overnight
  2. additionwas added until pH was about 3-4
  3. extractionThe aqueous layer was extracted with additional EtOAc
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customThe crude product was purified by silica gel chromatography (5-60% EtOAc/hexanes+1% AcOH)

출처 및 근거

ORD 기록
ord-c0d287f08fd8414f99c031490a760c0b
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09271970B2

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