1,2-Dichloroethane → 1,1-dimethylethyl (3R)-3-(cyclopentylmethyl)-4-[5-(4-morpholinylcarbonyl)-4,5-dihydro-1H-pyrazol-1-yl]-4-oxobutanoate

HRID 1396983ノート

反応式

HRID 1396983 の反応式
[CH:1]1([CH2:6][C@H:7]([CH2:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[C:8]([N:10]2[CH:14]([C:15](O)=[O:16])[CH2:13][CH:12]=[N:11]2)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.CCN(C(C)C)C(C)C.C(Cl)CCl.[NH:39]1[CH2:44][CH2:43][O:42][CH2:41][CH2:40]1>ClCCl>[CH:1]1([CH2:6][C@@H:7]([C:8]([N:10]2[CH:14]([C:15]([N:39]3[CH2:44][CH2:43][O:42][CH2:41][CH2:40]3)=[O:16])[CH2:13][CH:12]=[N:11]2)=[O:9])[CH2:18][C:19]([O:21][C:22]([CH3:24])([CH3:25])[CH3:23])=[O:20])[CH2:5][CH2:4][CH2:3][CH2:2]1

参加物

6

反応物 4

HCID 111,2-DichloroethaneHCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 682877191-{(2R)-2-(cyclopentylmethyl)-4-[(1,1-dimethylethyl)oxy]-4-oxobutanoyl}-4,5-dihydro-1H-pyrazole-5-carboxylic acid

生成物 1

HCID 682879911,1-dimethylethyl (3R)-3-(cyclopentylmethyl)-4-[5-(4-morpholinylcarbonyl)-4,5-dihydro-1H-pyrazol-1-yl]-4-oxobutanoate収率 58%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of 1-{(2R)-2-(cyclopentylmethyl)-4-[(1,1-dimethylethyl)oxy]-4-oxobutanoyl}-4,5-dihydro-1H-pyrazole-5-carboxylic acid (353 mg, 1.0 mmol), Hunig's base (0.35 ml, 2.0 mmol), EDC (231 mg, 1.2 mmol) and aza-HOBt (136 mg, 1.0 mmol) in dichloromethane (DCM) (10 ml) was added morpholine (0.131 ml, 1.5 mmol). The reaction mixture was stirred at room temperature overnight. After this time, the mixture was washed with water (5 mL) and NaHCO3 solution (5 mL×3), and concentrated to provide the crude product which was purified by Combiflash automated silica gel chromatography (0-100% EtOAc in hex) to afford 1,1-dimethylethyl (3R)-3-(cyclopentylmethyl)-4-[5-(4-morpholinylcarbonyl)-4,5-dihydro-1H-pyrazol-1-yl]-4-oxobutanoate (244 mg, 0.58 mmol, 58% yield) as a white solid. MS: 422 ([M+H]+).

後処理

  1. washAfter this time, the mixture was washed with water (5 mL) and NaHCO3 solution (5 mL×3)
  2. concentrationconcentrated
  3. customto provide the crude product which
  4. customwas purified by Combiflash automated silica gel chromatography (0-100% EtOAc in hex)

出典と根拠

ORDレコード
ord-68d96eb5d5824e26b11d26176def3337
出典データセット
uspto-grants-2014_12
特許番号
US08901119B2

反応ノート

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