1-Hydroxybenzotriazole → HCID 59275430, Verbindung

HRID 1672001Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1672001
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:20]=[CH:19][C:18]([C:21]4[CH:22]=[C:23]([CH:27]=[CH:28][C:29]=4[CH3:30])[C:24](O)=[O:25])=[CH:17][C:11]=3[C:12]=2[C:13](=[O:16])[NH:14][CH3:15])=[CH:4][CH:3]=1.[N:31]1[CH:36]=[C:35]([C:37]2([NH2:40])[CH2:39][CH2:38]2)[CH:34]=[N:33][CH:32]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.C(N(C(C)C)CC)(C)C>C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[O:9][C:10]3[CH:20]=[CH:19][C:18]([C:21]4[CH:22]=[C:23]([C:24](=[O:25])[NH:40][C:37]5([C:35]6[CH:36]=[N:31][CH:32]=[N:33][CH:34]=6)[CH2:39][CH2:38]5)[CH:27]=[CH:28][C:29]=4[CH3:30])=[CH:17][C:11]=3[C:12]=2[C:13]([NH:14][CH3:15])=[O:16])=[CH:6][CH:7]=1

Komponenten

7

Edukt 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 552962391-(Pyrimidin-5-yl)cyclopropan-1-amineHCID 592756533-(2-(4-Fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-4-methylbenzoic acid

Produkt 1

HCID 59275430HCID 59275430, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a mixture of 3-(2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-4-methylbenzoic acid (0.1 g, 0.25 mmol, 1 eq), 1-(pyrimidin-5-yl)cyclopropanamine (0.041 g, 0.3 mmol, 1.2 eq) (60% purity), HOBT (0.057 g, 0.42 mmol, 1.7 eq), EDC.HCl (0086 g, 0.44 mmol, 1.8 eq) in DCM at ambient temperature under nitrogen was added Diisopropylehtylamine (0.162 g, 1.2 mmol, 5.0 eq). The clear mixture was stirred at ambient temperature for overnight. The mixture was concentrated, diluted with water and extracted with EtOAc. The organic layer is further washed with water, dried over sodium sulphate and concentrated. The product obtained was further purified by column chromatography (neutral alumina) using 0.5% Methanol/DCM and finally it was purified by preparative HPLC. Yield: 0.02 g (20%). 1H NMR (400 MHz, DMSO-d6): δ 1.34-1.35 (m, 2H), 1.41-1.42 (m, 2H), 2.29 (s, 3H), 2.81-2.82 (d, 3H), J=4.56 Hz), 738-7.45 (m, 4H), 7.58 (d, 1H, J=0.96 Hz), 7.75 (d, 1H, J=8.4 Hz), 7.81 (s, 1H), 7.83 (m, 1H), 7.98-8.01 (m, 2H), 8.46-8.47 (d, 1H, J=4.6 Hz), 8.64 (s, 2H), 9.01 (s, 1H), 9.31 (s, 1H). LCMS: (ES+) m/z=521.2 (M+H). LCMS Method: Column-Ascentis Express C18 (5×2.1 mm-2.7 μm) Mphase A: 2% ACN-98% H2O-10 mM NH4COOH Mphase B: 98% ACN-2% H2O-10 mM NH4COOH Flow: 1 ML/Min

Aufarbeitung

  1. concentrationThe mixture was concentrated
  2. additiondiluted with water
  3. extractionextracted with EtOAc
  4. washThe organic layer is further washed with water
  5. dry with materialdried over sodium sulphate
  6. concentrationconcentrated
  7. customThe product obtained
  8. customwas further purified by column chromatography (neutral alumina)
  9. customwas purified by preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-08f81ce1073c4fc59fe1221810b439d1
Quelldatensatz
uspto-grants-2011_08
Patentnummer
US07994171B2

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