Trifluoroacetic acid → 2-(6-pyrrolidin-2-ylpyridin-3-yl)-1H-benzimidazole-4-carboxamide

HRID 564233Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 564233
C(OC([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[CH:21]=[CH:20][C:16]([C:17](O)=O)=[CH:15][N:14]=1)=O)(C)(C)C.C(N1C=CN=C1)(N1C=CN=C1)=O.Cl.Cl.[NH2:36][C:37]1[C:45]([NH2:46])=[CH:44][CH:43]=[CH:42][C:38]=1[C:39]([NH2:41])=[O:40].FC(F)(F)C(O)=O>N1C=CC=CC=1.CN(C)C=O.ClCCl>[NH:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[N:14]=[CH:15][C:16]([C:17]2[NH:46][C:45]3[CH:44]=[CH:43][CH:42]=[C:38]([C:39]([NH2:41])=[O:40])[C:37]=3[N:36]=2)=[CH:20][CH:21]=1

Komponenten

8

Edukt 4

HCID 6422Trifluoroacetic acidHCID 682631,1'-CarbonyldiimidazoleHCID 534228072,3-Diaminobenzamide dihydrochlorideHCID 667607276-(1-(Tert-butoxycarbonyl)pyrrolidin-2-yl)nicotinic acid

Produkt 1

HCID 667597102-(6-pyrrolidin-2-ylpyridin-3-yl)-1H-benzimidazole-4-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 1049PyridineLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
40 °C

Versuchsvorschrift

To a mixture of 6-(1-(tert-butoxycarbonyl)pyrrolidin-2-yl)nicotinic acid (3 g, 10.6 mmol) in pyridine (10 mL) and N,N-dimethylformamide (50 mL) at ambient temperature was added 1,1′-carbonyldiimidazole (2.2 g, 16 mmol). The mixture was heated at 40° C. for 1 hour, treated with 2,3-diaminobenzamide dihydrochloride (2.4 g, 10.6 mmol), stirred at ambient temperature, for 16 hours and concentrated. The residue was heated in acetic acid (100 mL) at 110° C. for 2 hours, cooled and concentrated. The residue was purified by flash chromatography on silica gel using ethyl acetate to provide the acyclic intermediate. This intermediate was dissolved in dichloromethane (100 mL) and trifluoroacetic acid (20 mL) and the mixture was stirred at room temperature for 16 hours and was concentrated. The residue was purified by HPLC (Zorbax C-8, 0.1% trifluoroacetic acid/acetonitrile/water) to provide the title compound. 1H NMR (methanol-d4) δ 2.04-2.36 (m, 3H), 2.49-2.74 (m, 1H), 3.39-3.72 (m, 2H), 4.98 (t, J=7.63 Hz, 1H), 7.17-7.49 (m, 1H), 7.69 (d, J=8.14 Hz, 1H), 7.81 (d, J=8.14 Hz, 1H), 7.99 (d, J=7.46 Hz, 1H), 8.64 (dd, J=8.31, 2.20 Hz, 1H), 9.42 (s, 1H).

Aufarbeitung

  1. concentrationconcentrated
  2. temperatureThe residue was heated in acetic acid (100 mL) at 110° C. for 2 hours
  3. temperaturecooled
  4. concentrationconcentrated
  5. customThe residue was purified by flash chromatography on silica gel
  6. customto provide the acyclic intermediate
  7. concentrationwas concentrated
  8. customThe residue was purified by HPLC (Zorbax C-8, 0.1% trifluoroacetic acid/acetonitrile/water)

Quellen und Nachweise

ORD-Eintrag
ord-bc23ca5d15db4ac59f413856420061ab
Quelldatensatz
uspto-grants-2011_11
Patentnummer
US08067613B2

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