Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → 3-(3,5-Difluoro-phenyl)-2-[(2-isoquinolin-3-yl-1h-benzoimidazole-4-carbonyl)-amino]-propionic acid methyl ester

HRID 1910113Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1910113
[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([C:11]2[NH:15][C:14]3[CH:16]=[CH:17][CH:18]=[C:19]([C:20](O)=[O:21])[C:13]=3[N:12]=2)[N:2]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[CH3:48][O:49][C:50](=[O:62])[CH:51]([NH2:61])[CH2:52][C:53]1[CH:58]=[C:57]([F:59])[CH:56]=[C:55]([F:60])[CH:54]=1>C(OCC)(=O)C>[CH3:48][O:49][C:50](=[O:62])[CH:51]([NH:61][C:20]([C:19]1[C:13]2[N:12]=[C:11]([C:3]3[N:2]=[CH:1][C:10]4[C:5]([CH:4]=3)=[CH:6][CH:7]=[CH:8][CH:9]=4)[NH:15][C:14]=2[CH:16]=[CH:17][CH:18]=1)=[O:21])[CH2:52][C:53]1[CH:54]=[C:55]([F:60])[CH:56]=[C:57]([F:59])[CH:58]=1

Komponenten

5

Edukt 3

HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66940454Methyl 2-amino-3-(3,5-difluorophenyl)propanoate hydrochlorideHCID 669406062-isoquinolin-3-yl-1H-benzoimidazole-4-carboxylic acid

Produkt 1

HCID 669403573-(3,5-Difluoro-phenyl)-2-[(2-isoquinolin-3-yl-1h-benzoimidazole-4-carbonyl)-amino]-propionic acid methyl esterAusbeute 50 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

145 mg (0.5 mmol) of 2-isoquinolin-3-yl-1H-benzoimidazole-4-carboxylic acid (synthesized in Example 1, Step 3)) was reacted with 280 mg (0.75 mmol) of HBTU and 2-amino-3-(3,5-difluoro-phenyl)-propionic acid methyl ester HCl salt (126 mg, 0.5 mmol) as described in general procedure A. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate (30 mL). The organic phase was washed with 1% NaOH aq. solution, then dried over Na2SO4 and concentrated under vacuum. The residue was purified by flash column chromatography (DCM/EtOAc=1:1 then DCM/EtOAc/MeOH=15:15:1) to give 3-(3,5-difluoro-phenyl)-2-[(2-isoquinolin-3-yl-1H-benzoimidazole-4-carbonyl)-amino]-propionic acid methyl ester (120 mg, 50%). LCMS: 487 (M+1)+.

Aufarbeitung

  1. washThe organic phase was washed with 1% NaOH aq. solution
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated under vacuum
  4. customThe residue was purified by flash column chromatography (DCM/EtOAc=1:1

Quellen und Nachweise

ORD-Eintrag
ord-861dd41bce3248d38985dddda92ef247
Quelldatensatz
uspto-grants-2013_12
Patentnummer
US08598353B2

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