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4-Methylmorpholine → (S)-N-((1S,2S)-1-((2R,4R)-1-(4-methoxybenzyl)-4-(allyloxy)pyrrolidin-2-yl)-3-(3,5-difluorophenyl)-1-hydroxypropan-2-yl)-2-((R)-3-acetamido-3-isobutyl-2-oxopyrrolidin-1-yl)-4-phenylbutanamide

HRID 132948
ノート
印刷プレビュー

反応式

HRID 132948 の反応式
[C:1]([NH:4][C@:5]1([CH2:23][CH:24]([CH3:26])[CH3:25])[CH2:9][CH2:8][N:7]([C@@H:10]([CH2:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:11](O)=[O:12])[C:6]1=[O:22])(=[O:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:51][O:52][C:53]1[CH:81]=[CH:80][C:56]([CH2:57][N:58]2[CH2:62][C@H:61]([O:63][CH2:64][CH:65]=[CH2:66])[CH2:60][C@@H:59]2[C@@H:67]([OH:79])[C@@H:68]([NH2:78])[CH2:69][C:70]2[CH:75]=[C:74]([F:76])[CH:73]=[C:72]([F:77])[CH:71]=2)=[CH:55][CH:54]=1.CN1CCOCC1>CN(C=O)C>[CH3:51][O:52][C:53]1[CH:81]=[CH:80][C:56]([CH2:57][N:58]2[CH2:62][C@H:61]([O:63][CH2:64][CH:65]=[CH2:66])[CH2:60][C@@H:59]2[C@@H:67]([OH:79])[C@@H:68]([NH:78][C:11](=[O:12])[C@@H:10]([N:7]2[CH2:8][CH2:9][C@:5]([NH:4][C:1](=[O:3])[CH3:2])([CH2:23][CH:24]([CH3:25])[CH3:26])[C:6]2=[O:22])[CH2:14][CH2:15][C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH2:69][C:70]2[CH:71]=[C:72]([F:77])[CH:73]=[C:74]([F:76])[CH:75]=2)=[CH:55][CH:54]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 4

HCID 79724-MethylmorpholineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58608197(1S,2S)-1-((2R,4R)-1-(4-methoxybenzyl)-4-(allyloxy)pyrrolidin-2-yl)-2-amino-3-(3,5-difluorophenyl)propan-1-olHCID 59733913(S)-2-((R)-3-acetamido-3-isobutyl-2-oxopyrrolidin-1-yl)-4-phenylbutanoic acid

生成物 1

HCID 69195642
(S)-N-((1S,2S)-1-((2R,4R)-1-(4-methoxybenzyl)-4-(allyloxy)pyrrolidin-2-yl)-3-(3,5-difluorophenyl)-1-hydroxypropan-2-yl)-2-((R)-3-acetamido-3-isobutyl-2-oxopyrrolidin-1-yl)-4-phenylbutanamide
収率 55.3%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

実験手順

Step 1 (A): To a solution of (S)-2-((R)-3-acetamido-3-isobutyl-2-oxopyrrolidin-1-yl)-4-phenylbutanoic acid (Preparation B, 96 mg, 0.266 mmol) in DMF (1.5 ml) was added HATU (121 mg, 0.319 mmol). A solution of (1S,2S)-1-((2R,4R)-1-(4-methoxybenzyl)-4-(allyloxy)pyrrolidin-2-yl)-2-amino-3-(3,5-difluorophenyl)propan-1-ol (Preparation C, 115 mg, 0.266 mmol) in DMF (1.0 ml) was then added, followed by N-methylmorpholine (102 μl, 0.931 mmol). The reaction mixture was stirred at rt for 30 min. pH 4 buffer was then added to quench. The mixture was extracted with ethyl acetate. The organic phase was washed with sat. aqueous NaCl, dried (MgSO4), and concentrated in vacuo. Flash chromatography (silica gel, 75-100% ethyl acetate/hexane) gave 114 mg (55%) of (S)-N-((1S,2S)-1-((2R,4R)-1-(4-methoxybenzyl)-4-(allyloxy)pyrrolidin-2-yl)-3-(3,5-difluorophenyl)-1-hydroxypropan-2-yl)-2-((R)-3-acetamido-3-isobutyl-2-oxopyrrolidin-1-yl)-4-phenylbutanamide as a clear, colorless oil:

後処理

  1. additionbuffer was then added
  2. customto quench
  3. extractionThe mixture was extracted with ethyl acetate
  4. washThe organic phase was washed with sat. aqueous NaCl
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-68bf58505f86480bb1a54345dabf7314
出典データセット
uspto-grants-2008_06
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07388007B2

反応ノート

読み込み中…

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