4-Methylmorpholine → (1RS,2S)-2-{(3RS)-4-Acetyl-3-isopropyl-2-oxo-6-phenyl-1,2,3,4-tetrahydropyrazin-1-yl}methylcarbonylamino-3-phenyl-1-(1,3-thiazol-2-yl)-1-propanol

HRID 1061683ノート

反応式

HRID 1061683 の反応式
CN1CCOCC1.[C:8]([N:11]1[CH:16]=[C:15]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:14]([CH2:23][C:24](O)=[O:25])[C:13](=[O:27])[CH:12]1[CH:28]([CH3:30])[CH3:29])(=[O:10])[CH3:9].ClC(OCC(C)C)=O.Cl.[NH2:40][C@@H:41]([CH2:49][C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1)[CH:42]([C:44]1[S:45][CH:46]=[CH:47][N:48]=1)[OH:43]>O1CCCC1.CS(C)=O.O>[C:8]([N:11]1[CH:16]=[C:15]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:14]([CH2:23][C:24]([NH:40][C@@H:41]([CH2:49][C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=2)[CH:42]([C:44]2[S:45][CH:46]=[CH:47][N:48]=2)[OH:43])=[O:25])[C:13](=[O:27])[CH:12]1[CH:28]([CH3:30])[CH3:29])(=[O:10])[CH3:9]

参加物

8

反応物 4

HCID 79724-Methylmorpholine2 回HCID 62365Isobutyl chloroformateHCID 22284314{(3RS)-4-Acetyl-3-isopropyl-2-oxo-6-phenyl-1,2,3,4-tetrahydropyrazin-1-yl}acetic acidHCID 69748243(1RS,2S)-2-amino-3-phenyl-1-(1,3-thiazol-2-yl)-1-propanol hydrochloride

生成物 1

HCID 60073849(1RS,2S)-2-{(3RS)-4-Acetyl-3-isopropyl-2-oxo-6-phenyl-1,2,3,4-tetrahydropyrazin-1-yl}methylcarbonylamino-3-phenyl-1-(1,3-thiazol-2-yl)-1-propanol

試薬・触媒・溶媒 3

HCID 679Dimethyl Sulfoxide溶媒HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-10 °C

実験手順

N-Methylmorpholine (66.4 μl) is added to a solution of {(3RS)-4-acetyl-3-isopropyl-2-oxo-6-phenyl-1,2,3,4-tetrahydropyrazin-1-yl}acetic acid (162 mg, Reference compound No. 51-1) in tetrahydrofuran (2.5 ml). The mixture is cooled to −10° C., isobutyl chloroformate (65.4 μl) is added to the mixture, and the whole is stirred for 15 minutes. A mixed solution of (1RS,2S)-2-amino-3-phenyl-1-(1,3-thiazol-2-yl)-1-propanol hydrochloride (150 mg, Reference compound No. 10-2) and N-methylmorpholine (132.6 μl) in tetrahydrofuran (2.5 ml) and dimethyl sulfoxide (1 ml) is added thereto, and the whole is stirred overnight. Water is added to the reaction mixture, and the whole is extracted with ethyl acetate. The extract is washed with an aqueous sodium hydrogencarbonate solution, water and saturated brine successively and dried over magnesium sulfate. The extract is concentrated under reduced pressure, and the resulting residue is purified by column chromatography to give the titled compound (162.9 mg).

後処理

  1. stirringthe whole is stirred overnight
  2. extractionthe whole is extracted with ethyl acetate
  3. washThe extract is washed with an aqueous sodium hydrogencarbonate solution, water and saturated brine successively
  4. dry with materialdried over magnesium sulfate
  5. concentrationThe extract is concentrated under reduced pressure
  6. customthe resulting residue is purified by column chromatography

出典と根拠

ORDレコード
ord-20062eec12b94237b3f5613ebb52f1fa
出典データセット
uspto-grants-2005_11
特許番号
US06960575B2

反応ノート

読み込み中…