3-Methyl-5-isoxazolecarboxylic acid → (R)-Methyl 3-(5-methyl isoxazole-3-carboxamido)-2,3-dihydro-1H-indene-5-carboxylate

HRID 1193269ノート

反応式

HRID 1193269 の反応式
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.[CH3:34][C:35]1[O:39][N:38]=[C:37]([C:40]([OH:42])=O)[CH:36]=1.[NH2:43][C@H:44]1[C:52]2[C:47](=[CH:48][CH:49]=[C:50]([C:53]([O:55][CH3:56])=[O:54])[CH:51]=2)[CH2:46][CH2:45]1>ClCCl>[CH3:34][C:35]1[O:39][N:38]=[C:37]([C:40]([NH:43][C@H:44]2[C:52]3[C:47](=[CH:48][CH:49]=[C:50]([C:53]([O:55][CH3:56])=[O:54])[CH:51]=3)[CH2:46][CH2:45]2)=[O:42])[CH:36]=1

参加物

6

反応物 4

HCID 769473-Methyl-5-isoxazolecarboxylic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 55278060(R)-Methyl 3-amino-2,3-dihydro-1H-indene-5-carboxylate

生成物 1

HCID 66798795(R)-Methyl 3-(5-methyl isoxazole-3-carboxamido)-2,3-dihydro-1H-indene-5-carboxylate収率 68%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒3 回

実験手順

HATU (4.4 g, 11.7 mmol, 1.5 eq) and DIPEA (3.0 ml, 15.6 mmol, 2 eq) were added to an ice-cooled solution of 5-methylisoxazole-3-carboxylic acid (990 mg, 7.8 mmol, 1 eq) in dichloromethane (80 ml), and stirring was carried out for 30 min. (R)-Methyl 3-amino-2,3-dihydro-1H-indene-5-carboxylate (A-07) (7.8 mmol, 1 eq) was dissolved in dichloromethane (20 ml) and added dropwise to the reaction solution, and stirring was carried out for 16 h at RT. The reaction solution was diluted with dichloromethane (250 ml), washed with sat. sodium hydrogen carbonate solution (50 ml), sat. ammonium chloride solution (50 ml), water (50 ml) and sat. NaCl solution (50 ml), dried over sodium sulfate and concentrated under reduced pressure. After purification by column chromatography (silica gel, 2% MeOH in dichloro-methane), the desired product was obtained in the form of a yellowish solid. Yield: 68% (1.6 g, 5.3 mmol).

後処理

  1. additionadded dropwise to the reaction solution
  2. stirringstirring
  3. waitwas carried out for 16 h at RT
  4. washwashed with sat. sodium hydrogen carbonate solution (50 ml), sat. ammonium chloride solution (50 ml), water (50 ml) and sat. NaCl solution (50 ml)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customAfter purification by column chromatography (silica gel, 2% MeOH in dichloro-methane)

出典と根拠

ORDレコード
ord-ac9b345feb254794b0b10f4174186e12
出典データセット
uspto-grants-2014_03
特許番号
US08680159B2

反応ノート

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