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

HRID 1688389
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Druckvorschau

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Reaktionsgleichung von HRID 1688389
[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[CH:23]=[C:24]([CH:28]=[CH:29][C:30]=1[CH3:31])[C:25]([OH:27])=O.Cl.[N:33]1[CH:38]=[CH:37][C:36]([C:39]2([NH2:42])[CH2:41][CH2:40]2)=[N:35][CH:34]=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:23]=[C:24]([C:25](=[O:27])[NH:42][C:39]2([C:36]3[CH:37]=[CH:38][N:33]=[CH:34][N:35]=3)[CH2:41][CH2:40]2)[CH:28]=[CH:29][C:30]=1[CH3:31]
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Komponenten

6

Edukt 3

HCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 592756803-(4-Fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-4-methylbenzoic acidHCID 672924411-(Pyrimidin-4-yl)cyclopropan-1-amine hydrochloride

Produkt 1

HCID 534682484-Fluoro-2-(4-fluorophenyl)-N-methyl-5-(2-methyl-5-(1-(pyrimidin-4-yl)-cyclopropylcarbamoyl)phenyl)benzofuran-3-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a mixture of 3-(4-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-4-methylbenzoic acid (0.050 g, 0.114 mmol, 1.0 eq), 1-(pyrimidin-4-yl)cyclopropanamine HCl (0.015 g, 0.113 mmol, 1.0 eq) in DMF at 0° C. was added TEA (0.060 g, 0.594 mmol, 5.0 eq) and BOP reagent (0.076 g, 0.172 mmol, 1.5 eq). The reaction mixture was stirred 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 preparative HPLC. Yield: 0.035 g (57.37%). 1H NMR (400 MHz, CD3OD): δ 9.00 (d, J=1.2 Hz, 1H), 8.60 (d, J=5.6 Hz, 1H), 7.98-7.90 (m and dd, 3H), 7.85 (d, J=2.0 Hz, 1H), 7.56 (d, J=8.4 Hz, 1H), 7.51-7.49 (two overlapping d, 2H), 7.35-7.28 (m, 3H), 2.96 (s, 3H), 2.30 (s, 3H), 1.84-1.81 (m, 2H), 1.52-1.49 (m, 2H). 19F NMR (376.57 MHz, CD3OD): δ −76.94 (TFA), −112.22, −122.76 LCMS: (ES+) m/z=539.2 (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 preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-f6bc1b985a494bb599a4dbc435983ec5
Quelldatensatz
uspto-grants-2012_04
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08148382B2

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