1,2-Dichloroethane → 1,1-dimethylethyl (3R)-3-(cyclopentyl methyl)-4-{5-[(dimethylamino)carbonyl]-4,5-dihydro-1H-pyrazol-1-yl}-4-oxobutanoate

HRID 1396979ノート

反応式

HRID 1396979 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.C[CH2:27][N:28](C(C)C)[CH:29](C)C.C(Cl)CCl.CNC>ClCCl.C1COCC1>[CH:1]1([CH2:6][C@@H:7]([C:8]([N:10]2[CH:14]([C:15]([N:28]([CH3:29])[CH3:27])=[O:16])[CH2:13][CH:12]=[N:11]2)=[O:9])[CH2:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:5][CH2:4][CH2:3][CH2:2]1

参加物

7

反応物 4

HCID 111,2-DichloroethaneHCID 674DimethylamineHCID 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 682880781,1-dimethylethyl (3R)-3-(cyclopentyl methyl)-4-{5-[(dimethylamino)carbonyl]-4,5-dihydro-1H-pyrazol-1-yl}-4-oxobutanoate収率 83%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran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 N-methylmethanamine (1.0 ml, 2.0 mmol), which was in THF. The reaction mixture was stirred at room temperature overnight. The mixture was then washed with water (5 mL), NaHCO3 solution (5 mL×3), and concentrated to provide the crude product which was purified by Combiflash automated silica gel chromatography (0-50% EtOAc in hex) to afford 1,1-dimethylethyl (3R)-3-(cyclopentyl methyl)-4-{5-[(dimethylamino)carbonyl]-4,5-dihydro-1H-pyrazol-1-yl}-4-oxobutanoate (315 mg, 0.83 mmol, 83% yield) as a yellow solid. MS: 380 ([M+H]+).

後処理

  1. washThe mixture was then washed with water (5 mL), NaHCO3 solution (5 mL×3)
  2. concentrationconcentrated
  3. customto provide the crude product which
  4. customwas purified by Combiflash automated silica gel chromatography (0-50% EtOAc in hex)

出典と根拠

ORDレコード
ord-5af7b5569df34929a520738fb60257b9
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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