1-Hydroxybenzotriazole → N-((1R)-1-(N-((1R)-2-(2-Fluorophenyl)-1-(methylcarbamoyl)ethyl)-N-methyl-carbamoyl)-2-(2-naphthyl)ethyl)-N-methylcarbamic acid tert-butylester

HRID 495789

反応式

HRID 495789 の反応式
[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].ON1C2C=CC=C[C:17]=2N=N1.Cl.CN(C)CCCN=C=NCC.[F:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=1[CH2:42][C@@H:43]([NH:48][CH3:49])[C:44]([NH:46][CH3:47])=[O:45].C(N(C(C)C)CC)(C)C.C(OC(CNC([CH2:72][C:73]1[CH:82]=[CH:81][C:80]2[C:75](=[CH:76][CH:77]=[CH:78][CH:79]=2)[CH:74]=1)C(O)=O)=O)(C)(C)C.ON1C2N=CC=CC=2N=N1>C(Cl)Cl>[C:1]([O:5][C:6](=[O:7])[N:8]([C@@H:9]([C:10](=[O:12])[N:48]([C@@H:43]([C:44](=[O:45])[NH:46][CH3:47])[CH2:42][C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][C:36]=1[F:35])[CH3:49])[CH2:72][C:73]1[CH:82]=[CH:81][C:80]2[C:75](=[CH:76][CH:77]=[CH:78][CH:79]=2)[CH:74]=1)[CH3:17])([CH3:2])([CH3:3])[CH3:4]

参加物

9

反応物 7

HCID 757711-HydroxybenzotriazoleHCID 78288N-(tert-butoxycarbonyl)glycineHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2 回HCID 223270012-(Tert-butoxycarbonylmethylamino)-3-(2-naphthyl)propionic acidHCID 54111884(2R)-3-(2-Fluorophenyl)-N-methyl-2-(methylamino)propionamide

生成物 1

HCID 53671638N-((1R)-1-(N-((1R)-2-(2-Fluorophenyl)-1-(methylcarbamoyl)ethyl)-N-methyl-carbamoyl)-2-(2-naphthyl)ethyl)-N-methylcarbamic acid tert-butylester収率 69%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒3 回

実験手順

Tert-Butoxycarbonylaminoacetic acid (0.18 g; 2.39 mmol) was dissolved in methylene chloride (20 mL). 1-Hydroxybenzotriazole (0.32 g; 2.39 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.55 g; 2.87 mmol) were added and the reaction mixture was stirred for 15 min at room temperature. (2R)-3-(2-Fluorophenyl)-N-methyl-2-(methylamino)propionamide (1.0 g; 4.78 mmol) and diisopropylethylamine (0.9 mL; 5.26 mmol) was added and the reaction mixture was stirred for 12 hours at room temperature. A mixture of 2-(tert-butoxycarbonylmethylamino)-3-(2-naphthyl)propionic acid (0.78 g; 2.39 mmol), 1-hydroxy-7-azabenzotriazole (0.33 g; 2.39 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.55 g; 2.87 mmol) were dissolved in methylene chloride (20 mL) and added to the reaction mixture. The reaction mixture was stirred for 12 hours at room temperature. Methylene chloride (50 mL) was added and the reaction mixture was washed with water (30 mL), an aqueous solution of sodium hydrogen sulfate (10%; 30 mL), an aqueous solution of sodium hydrogen carbonate/sodium carbonate (pH 9; 30 mL) and water (30 mL) and dried (magnesium sulfate). The solvent was removed in vacuo and the residue was chromatographed on silica (2.5×30 cm) using ethyl acetate/heptane (2:1) as eluent to afford 0.86 g of N-((1R)-1-(N-((1R)-2-(2-fluorophenyl)-1-(methylcarbamoyl)ethyl)-N-methylcarbamoyl)-2-(2-naphthyl)ethyl)-N-methyl-carbamic acid tert-butylester.

後処理

  1. stirringthe reaction mixture was stirred for 12 hours at room temperature
  2. additionadded to the reaction mixture
  3. stirringThe reaction mixture was stirred for 12 hours at room temperature
  4. washthe reaction mixture was washed with water (30 mL)
  5. dry with materialan aqueous solution of sodium hydrogen sulfate (10%; 30 mL), an aqueous solution of sodium hydrogen carbonate/sodium carbonate (pH 9; 30 mL) and water (30 mL) and dried (magnesium sulfate)
  6. customThe solvent was removed in vacuo
  7. customthe residue was chromatographed on silica (2.5×30 cm)

出典と根拠

ORDレコード
ord-d64104bcf41b4169b1ca0270290a763d
出典データセット
uspto-grants-2005_09
特許番号
US06939880B2

関連ノート

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