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

HRID 1411022ノート

反応式

HRID 1411022 の反応式
[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]([C:55]1([NH2:58])[CH2:57][CH2:56]1)=[O:54])[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]([C:55]1([NH:58][C:24]([C:14]2[C:13]([OH:27])=[C:12]3[C:17](=[C:16]([C:18]4[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=4)[N:15]=2)[N:8]([CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[C:9](=[O:34])[C:10]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[CH:11]3)=[O:26])[CH2:57][CH2:56]1)=[O:54])[CH3:51]

参加物

10

反応物 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 386203Ethyl 1-aminocyclopropane-1-carboxylate hydrochlorideHCID 682974401-Benzyl-5-hydroxy-2-oxo-3-phenyl-8-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid

生成物 1

HCID 682976101-[(1-Benzyl-5-hydroxy-2-oxo-3-phenyl-8-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-cyclopropanecarboxylic acid ethyl ester収率 36.3%

試薬・触媒・溶媒 4

HCID 313Hydrochloric Acid溶媒HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒HCID 57417360Sodium chloride; water溶媒

実験手順

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. 1-Amino-cyclopropanecarboxylic acid ethyl ester HCl salt (31 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 (5-80% EtOAc/hexanes+1% AcOH) to give 24 mg of the title compound. MS: (+) m/z 561.40 (M+1).

後処理

  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 (5-80% EtOAc/hexanes+1% AcOH)

出典と根拠

ORDレコード
ord-18534bbd74644cc48d7298d3f07d1fad
出典データセット
uspto-grants-2014_12
特許番号
US08921389B2

反応ノート

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