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Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate → 4-Fluoro-2-(4-fluorophenyl)-5-(4-methoxy-2-methyl-5-(1-(pyrimidin-4-yl)cyclopropylcarbamoyl)phenyl)-N-methylbenzofuran-3-carboxamide

HRID 1672075
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Druckvorschau

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Reaktionsgleichung von HRID 1672075
[F:1][C:2]1[C:7]2[C:8]([C:18](=[O:21])[NH:19][CH3:20])=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[O:10][C:6]=2[CH:5]=[CH:4][C:3]=1[C:22]1[C:23]([CH3:33])=[CH:24][C:25]([O:31][CH3:32])=[C:26]([CH:30]=1)[C:27](O)=[O:28].Cl.[N:35]1[CH:40]=[CH:39][C:38]([C:41]2([NH2:44])[CH2:43][CH2:42]2)=[N:37][CH:36]=1.CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.O>[F:1][C:2]1[C:7]2[C:8]([C:18]([NH:19][CH3:20])=[O:21])=[C:9]([C:11]3[CH:12]=[CH:13][C:14]([F:17])=[CH:15][CH:16]=3)[O:10][C:6]=2[CH:5]=[CH:4][C:3]=1[C:22]1[CH:30]=[C:26]([C:27](=[O:28])[NH:44][C:41]2([C:38]3[CH:39]=[CH:40][N:35]=[CH:36][N:37]=3)[CH2:43][CH2:42]2)[C:25]([O:31][CH3:32])=[CH:24][C:23]=1[CH3:33]
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Komponenten

6

Edukt 3

HCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 592754645-(4-Fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl) 2-methoxy-4-methylbenzoic acidHCID 672924411-(Pyrimidin-4-yl)cyclopropan-1-amine hydrochloride

Produkt 1

HCID 534680294-Fluoro-2-(4-fluorophenyl)-5-(4-methoxy-2-methyl-5-(1-(pyrimidin-4-yl)cyclopropylcarbamoyl)phenyl)-N-methylbenzofuran-3-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a mixture of 5-(4-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-2-methoxy-4-methylbenzoic acid (0.080 g, 0.185 mmol, 1.0 eq), 1-(pyrimidin-4-yl)cyclopropanamine HCl (0.025 g, 0.185 mmol, 1.0 eq) in DMF and at 0° C. was added TEA (0.094 g, 0.930 mmol, 5.0 eq) and BOP reagent (0.120 g, 0.271 mmol, 1.5 eq). The reaction mixture was warmed to RT, and stirring was continued at RT overnight. The reaction mixture was diluted with water and extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4, filtered and concentrated. The crude product was purified by prep HPLC. Yield: 0.058 g (58.0%). 1H NMR (400 MHz, CD3OD): δ 9.03 (s, 1H), 8.64 (d, J=1.4 Hz, 1H), 7.97-7.79 (m., 2H), 7.76 (s, 1H), 7.65 (d, J=5.6 Hz, 1H), 7.52 (d, J=8.4 Hz, 1H), 7.31-7.25 (m, 3H), 7.19 (s, 1H), 4.09 (s, 3H), 2.95 (s, 3H), 2.30 (s, 3H), 1.88-1.85 (m, 2H), 1.55-1.52 (m, 2H). 19F NMR (376.57 MHz, CD3OD): δ−77.58 (TFA), −112.32, −122.76. LCMS: (ES+) m/z=569.2 (M+H)+

Aufarbeitung

  1. extractionextracted with EtOAc
  2. washThe organic layer was washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified by prep HPLC

Quellen und Nachweise

ORD-Eintrag
ord-bc348cb389254195a8caae5a9f87ebf4
Quelldatensatz
uspto-grants-2011_08
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US07994171B2

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