Hydrochloric Acid → 4-[2-(4-Bromo-phenyl)-2-oxo-ethylcarbamoyl]-3-(2-methoxycarbonylamino-3-methyl-butyryl)-imidazolidine-1-carboxylic acid tert-butyl ester

HRID 71795

反応式

HRID 71795 の反応式
CO[C:3]([CH:5]1[CH2:9][N:8]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:7][N:6]1[C:17](=[O:27])[CH:18]([NH:22][C:23]([O:25][CH3:26])=[O:24])[CH:19]([CH3:21])[CH3:20])=[O:4].[Li+].[OH-].Cl.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.Cl.[NH2:65][CH2:66][C:67]([C:69]1[CH:74]=[CH:73][C:72]([Br:75])=[CH:71][CH:70]=1)=[O:68]>C1COCC1.CO>[C:13]([O:12][C:10]([N:8]1[CH2:9][CH:5]([C:3](=[O:4])[NH:65][CH2:66][C:67]([C:69]2[CH:74]=[CH:73][C:72]([Br:75])=[CH:71][CH:70]=2)=[O:68])[N:6]([C:17](=[O:27])[CH:18]([NH:22][C:23]([O:25][CH3:26])=[O:24])[CH:19]([CH3:20])[CH3:21])[CH2:7]1)=[O:11])([CH3:15])([CH3:16])[CH3:14]

参加物

9

反応物 6

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 81531DiisopropylethylamineHCID 27982162-Amino-1-(4-bromophenyl)ethan-1-one hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 666211143-(2-Methoxycarbonylamino-3-methyl-butyryl)-imidazolidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-methyl ester

生成物 1

HCID 666206294-[2-(4-Bromo-phenyl)-2-oxo-ethylcarbamoyl]-3-(2-methoxycarbonylamino-3-methyl-butyryl)-imidazolidine-1-carboxylic acid tert-butyl ester収率 107.6%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

3-(2-Methoxycarbonylamino-3-methyl-butyryl)-imidazolidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-methyl ester (460 mg, 1.18 mmol) was dissolved in THF (3 mL) and MeOH (2 mL). An aqueous solution of LiOH (49.8 mg, 1.18 mmol) was added and stirring at room temperature was continued. After the hydrolysis was complete, the reaction was neutralized with aqueous HCl (1.18 mL, 1M). The organic solvents were removed in vacuo and the aqueous suspension was frozen and lyophilized. The crude material was used in the next step without further purification. The crude material was dissolved in DMF (4.0 mL) and HATU (448 mg, 1.18 mmol) and DIEA (152 mg, 1.18 mmol) were added. The reaction was stirred at room temperature for five minutes, after which the amino-(4′bromo) acetophenone hydrochloride salt (295 mg, 1.18 mmol) was added. Stirring at room temperature was continued. After 90 minutes, all volatiles were removed in vacuo and the crude material was purified via silica gel chromatography (eluent: EtOAc/hexanes) to yield the slightly impure product 4-[2-(4-Bromo-phenyl)-2-oxo-ethylcarbamoyl]-3-(2-methoxycarbonylamino-3-methyl-butyryl)-imidazolidine-1-carboxylic acid tert-butyl ester (723 mg): LCMS-ESI+: calc'd for C24H33BrN4O7: 569.4 (M+). Found: 570.4/572.4 (M+H+).

後処理

  1. customThe organic solvents were removed in vacuo
  2. temperaturethe aqueous suspension was frozen
  3. customThe crude material was used in the next step without further purification
  4. dissolutionThe crude material was dissolved in DMF (4.0 mL)
  5. stirringThe reaction was stirred at room temperature for five minutes
  6. stirringStirring at room temperature
  7. customall volatiles were removed in vacuo
  8. customthe crude material was purified via silica gel chromatography (eluent: EtOAc/hexanes)

出典と根拠

ORDレコード
ord-a93eb2602c944e5b9deb3f2588851b41
出典データセット
uspto-grants-2014_09
特許番号
US08822430B2

関連ノート

読み込み中…