1-Hydroxybenzotriazole → HCID 59620342、化合物

HRID 2070148ノート

反応式

HRID 2070148 の反応式
Cl.Cl.[NH2:3][CH:4]1[CH2:13][C:12]2[C:7](=[C:8]([NH2:14])[CH:9]=[CH:10][CH:11]=2)[NH:6][C:5]1=[O:15].O.[C:17]([O:21][C:22]([NH:24][C@@H:25]([C:30](O)=[O:31])[CH2:26][CH:27]([CH3:29])[CH3:28])=[O:23])([CH3:20])([CH3:19])[CH3:18].ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.C(=O)(O)[O-].[Na+]>CN(C=O)C.O.C(OCC)(=O)C.C(N(CC)CC)C>[NH2:14][C:8]1[CH:9]=[CH:10][CH:11]=[C:12]2[C:7]=1[NH:6][C:5](=[O:15])[CH:4]([NH:3][C:30](=[O:31])[C@H:25]([NH:24][C:22](=[O:23])[O:21][C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:26][CH:27]([CH3:29])[CH3:28])[CH2:13]2

参加物

10

反応物 5

HCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2724763D-Leucine, N-[(1,1-dimethylethoxy)carbonyl]-, monohydrateHCID 68412119HCID 68412119、化合物

生成物 1

HCID 59620342HCID 59620342、化合物収率 88.3%

試薬・触媒・溶媒 4

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8471Triethylamine溶媒HCID 8857Ethyl Acetate溶媒

実験手順

3,8-Diamino-3,4-dihydroquinolin-2(1H)-one dihydrochloride (9.0 g) was suspended in N,N-dimethylformaldehyde (90 mL), and triethylamine (15 mL) was added to the suspension under cooling on ice. Subsequently, N-tert-butoxycarbonyl-D-leucine monohydrate (9.87 g), 1-hydroxybenzotriazole (4.86 g), and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (7.67 g) were sequentially added to the mixture, followed by stirring at room temperature for one hour. To the resultant mixture were added saturated aqueous sodium bicarbonate solution, ethyl acetate, and water, and the mixture was subjected to extraction. The organic layer was sequentially washed with water and saturated aqueous sodium chloride solution, and was dried over sodium sulfate. The solvent was evaporated under reduced pressure, and the precipitates were filtered by use of ethyl acetate, whereby tert-butyl (2R)-1-(8-amino-2-oxo-1,2,3,4-tetrahydroquinolin-3-ylamino)-4-methyl-1-oxopentan-2-ylcarbamate (12.4 g) was yielded as a diastereomeric mixture. Subsequently, the thus-obtained tert-butyl (2R)-1-(8-amino-2-oxo-1,2,3,4-tetrahydroquinolin-3-ylamino)-4-methyl-1-oxopentan-2-ylcarbamate (7.68 g) was dissolved in ethanol (77 mL), and concentrated hydrochloric acid (34 mL) was added thereto, followed by heating to 60° C. while being stirred for 30 minutes. The resultant mixture was neutralized with saturated aqueous sodium bicarbonate solution under cooling on ice and was then subjected to extraction with chloroform. The organic layer was washed with saturated aqueous sodium chloride solution and dried over sodium sulfate. The solvent was evaporated under reduced pressure, and the thus-recovered residue was purified through silica gel column chromatography (chloroform:methanol=15:1), whereby the title compound (diastereomer of lower polarity: 2.85 g, diastereomer of higher polarity: 2.73 g) was yielded.

後処理

  1. temperatureunder cooling on ice
  2. extractionthe mixture was subjected to extraction
  3. washThe organic layer was sequentially washed with water and saturated aqueous sodium chloride solution
  4. dry with materialwas dried over sodium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. filtrationthe precipitates were filtered by use of ethyl acetate

出典と根拠

ORDレコード
ord-4e42950a4b5d43fbbe864f5cd377bf93
出典データセット
uspto-grants-2012_10
特許番号
US08299255B2

反応ノート

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