Hydrochloric Acid → {1-[5-[2-(4-Bromo-phenyl)-2-oxo-ethylcarbamoyl]-3-(2,2,2-trifluoro-ethyl)-imidazolidine-1-carbonyl]-2-methyl-propyl}-carbamic acid methyl ester

HRID 71801

反応式

HRID 71801 の反応式
CO[C:3]([CH:5]1[CH2:9][N:8]([CH2:10][C:11]([F:14])([F:13])[F:12])[CH2:7][N:6]1[C:15](=[O:25])[CH:16]([NH:20][C:21]([O:23][CH3:24])=[O:22])[CH:17]([CH3:19])[CH3:18])=[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.[NH2:63][CH2:64][C:65]([C:67]1[CH:72]=[CH:71][C:70]([Br:73])=[CH:69][CH:68]=1)=[O:66]>C1COCC1.CO>[CH3:24][O:23][C:21](=[O:22])[NH:20][CH:16]([C:15]([N:6]1[CH:5]([C:3](=[O:4])[NH:63][CH2:64][C:65]([C:67]2[CH:72]=[CH:71][C:70]([Br:73])=[CH:69][CH:68]=2)=[O:66])[CH2:9][N:8]([CH2:10][C:11]([F:14])([F:12])[F:13])[CH2:7]1)=[O:25])[CH:17]([CH3:18])[CH3:19]

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 666201763-(2-Methoxycarbonylamino-3-methyl-butyryl)-1-(2,2,2-trifluoro-ethyl)-imidazolidine-4-carboxylic acid methyl ester

生成物 1

HCID 66620808{1-[5-[2-(4-Bromo-phenyl)-2-oxo-ethylcarbamoyl]-3-(2,2,2-trifluoro-ethyl)-imidazolidine-1-carbonyl]-2-methyl-propyl}-carbamic acid methyl ester収率 104.4%

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)-1-(2,2,2-trifluoro-ethyl)-imidazolidine-4-carboxylic acid methyl ester (95 mg, 0.257 mmol) was dissolved in THF (1.8 mL) and MeOH (0.9 mL). An aqueous solution of LiOH (10.8 mg, 0.208 mmol) was added and stirring at room temperature was continued. After the hydrolysis was complete, the reaction was neutralized with aqueous HCl (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 (1.5 mL) and HATU (97.6 mg, 0.257 mmol) and DIEA (66.3 mg, 0.514 mmol) were added. The reaction was stirred at room temperature for five minutes, after which the amino-(4′bromo) acetophenone hydrochloride salt (64.2 mg, 0.257 mmol) was added. Stirring at room temperature was continued. After 60 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 {1-[5-[2-(4-Bromo-phenyl)-2-oxo-ethylcarbamoyl]-3-(2,2,2-trifluoro-ethyl)-imidazolidine-1-carbonyl]-2-methyl-propyl}-carbamic acid methyl ester (148 mg): LCMS-ESI+: calc'd for C21H26BrF3N4O5: 551.3 (M+). Found: 551.2/553.2 (M+).

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 (1.5 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-15b9a3f8dbab4e319af45c84aeb9bfcb
出典データセット
uspto-grants-2014_09
特許番号
US08822430B2

関連ノート

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