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Hydrochloric Acid → methyl (R)-2-oxo-1-phenyl-2-((S)-2-(5-(4-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[b]thiophen-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidin-1-yl)ethylcarbamate

HRID 1751406
ノート
印刷プレビュー

反応式

HRID 1751406 の反応式
Cl.[CH3:2][C:3]1([CH3:42])[C:7]([CH3:9])([CH3:8])[O:6][B:5]([C:10]2[CH:11]=[CH:12][C:13]3[CH:17]=[C:16]([C:18]4[CH:23]=[CH:22][C:21]([C:24]5[NH:28][C:27]([C@@H:29]6[CH2:33][CH2:32][CH2:31][N:30]6C(OC(C)(C)C)=O)=[N:26][CH:25]=5)=[CH:20][CH:19]=4)[S:15][C:14]=3[CH:41]=2)[O:4]1.CN1CCOCC1.CCOC(C(C#N)=NOC(N1CCOCC1)=[N+](C)C)=O.F[P-](F)(F)(F)(F)F.[CH3:77][O:78][C:79]([NH:81][C@H:82]([C:86]1[CH:91]=[CH:90][CH:89]=[CH:88][CH:87]=1)[C:83](O)=[O:84])=[O:80]>O1CCOCC1.ClCCl.C(OCC)(=O)C>[O:84]=[C:83]([N:30]1[CH2:31][CH2:32][CH2:33][C@H:29]1[C:27]1[NH:28][C:24]([C:21]2[CH:20]=[CH:19][C:18]([C:16]3[S:15][C:14]4[CH:41]=[C:10]([B:5]5[O:6][C:7]([CH3:9])([CH3:8])[C:3]([CH3:42])([CH3:2])[O:4]5)[CH:11]=[CH:12][C:13]=4[CH:17]=3)=[CH:23][CH:22]=2)=[CH:25][N:26]=1)[C@H:82]([NH:81][C:79](=[O:80])[O:78][CH3:77])[C:86]1[CH:91]=[CH:90][CH:89]=[CH:88][CH:87]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

9

反応物 5

HCID 313Hydrochloric AcidHCID 79724-Methylmorpholine2 回HCID 10910775(alphaR)-alpha-((Methoxycarbonyl)amino)benzeneacetic acidHCID 69676593(S)-tert-butyl 2-(5-(4-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[b]thiophen-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylateHCID 75951468(1-Cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphate

生成物 1

HCID 86708731methyl (R)-2-oxo-1-phenyl-2-((S)-2-(5-(4-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[b]thiophen-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidin-1-yl)ethylcarbamate収率 69.6%

試薬・触媒・溶媒 3

HCID 6344Dichloromethane溶媒2 回HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

実験手順

A solution of hydrogen chloride in dioxane (4 N, 5 mL) was added to a solution of (S)-tert-butyl 2-(5-(4-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[b]thiophen-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (328 mg, 0.56 mmol) in dichloromethane (5 mL). Gas evolution was observed. After 20 min the solvent was removed under reduced pressure and the residue was placed under high vacuum for 30 min. The solid was taken up in N,N-dimethylformamide (3 mL) and N-methylmorpholine (158 μL, 1.43 mmol) was added to the solution. In a separate vessel, COMU (258 mg, 0.605 mmol), and N-methylmorpholine (158 μL, 1.43 mmol) were added to a solution of (R)-2-(methoxycarbonylamino)-2-phenylacetic acid (126 mg, 0.604 mmol) in dichloromethane (3 mL). This was stirred for 5 minutes and both solutions were combined. After 15 minutes the mixture was diluted with ethyl acetate (20 mL) and washed with water (5 mL) and brine (5 mL). The organic phase was dried over sodium sulfate and filtered. The solvent was removed under reduced pressure and the residue was subjected to flash chromatography with eluant of (10% methanol in ethyl acetate) and hexane. The product containing fractions were combined and the solvent was removed under reduced pressure to provide methyl (R)-2-oxo-1-phenyl-2-((S)-2-(5-(4-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[b]thiophen-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidin-1-yl)ethylcarbamate (261 mg, 0.39 mmol, 69%).

後処理

  1. customAfter 20 min the solvent was removed under reduced pressure
  2. washwashed with water (5 mL) and brine (5 mL)
  3. dry with materialThe organic phase was dried over sodium sulfate
  4. filtrationfiltered
  5. customThe solvent was removed under reduced pressure
  6. additionThe product containing fractions
  7. customthe solvent was removed under reduced pressure

出典と根拠

ORDレコード
ord-58cb4ddbfe8949cd84f48418a6688da1
出典データセット
uspto-grants-2015_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09156823B2

反応ノート

読み込み中…

このページの内容参加物実験手順後処理出典と根拠反応ノート