1,1'-Carbonyldiimidazole → 4-[Bis-(3-methyl-pyridin-2-ylmethyl)-amino]-piperidine-1-carboxylic acid (1-methyl-1H-benzoimidazol-2-yl)-amide

HRID 251151

Reaktionsgleichung

Reaktionsgleichung von HRID 251151
[C:1](N1C=CN=C1)(N1C=CN=C1)=[O:2].[NH2:13][C:14]1[N:18]([CH3:19])[C:17]2[CH:20]=[CH:21][CH:22]=[CH:23][C:16]=2[N:15]=1.CCN(C(C)C)C(C)C.[CH3:33][C:34]1[C:35]([CH2:40][N:41]([CH2:48][C:49]2[C:54]([CH3:55])=[CH:53][CH:52]=[CH:51][N:50]=2)[CH:42]2[CH2:47][CH2:46][NH:45][CH2:44][CH2:43]2)=[N:36][CH:37]=[CH:38][CH:39]=1>CN(C=O)C>[CH3:19][N:18]1[C:17]2[CH:20]=[CH:21][CH:22]=[CH:23][C:16]=2[N:15]=[C:14]1[NH:13][C:1]([N:45]1[CH2:46][CH2:47][CH:42]([N:41]([CH2:48][C:49]2[C:54]([CH3:55])=[CH:53][CH:52]=[CH:51][N:50]=2)[CH2:40][C:35]2[C:34]([CH3:33])=[CH:39][CH:38]=[CH:37][N:36]=2)[CH2:43][CH2:44]1)=[O:2]

Komponenten

6

Edukt 4

HCID 682631,1'-CarbonyldiimidazoleHCID 741872-Amino-1-methylbenzimidazoleHCID 81531Diisopropylethylamine2×HCID 58996965Bis-(3-methyl-pyridin-2-ylmethyl)-piperidin-4-yl-amine

Produkt 1

HCID 589970074-[Bis-(3-methyl-pyridin-2-ylmethyl)-amino]-piperidine-1-carboxylic acid (1-methyl-1H-benzoimidazol-2-yl)-amideAusbeute 27 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A solution of 1,1′-carbonyldiimidazole (80.1 mg, 0.494 mmol), 2-amino-1-methylbenzimidazole (70.8 mg, 0.481 mmol), and DIPEA (0.17 mL, 0.97 mmol) in DMF (5 mL) was stirred at room temperature for 2.5 h. To this solution was added DIPEA (0.17 mL, 0.97 mmol) and COMPOUND 249 (149 mg, 0.479 mmol), and the resultant solution was stirred at 60° C. overnight. The solution was concentrated to dryness, treated with saturated aqueous NaHCO3 (30 mL), and extracted with CH2Cl2 (3×15 mL). The combined organic extracts were dried (Na2SO4), filtered, and concentrated. Purification of the crude material by flash chromatography on silica gel (CH2Cl2/MeOH/NH4OH, 92:4:4) provided COMPOUND 290 (62 mg, 27%) as a white solid. 1H NMR (CDCl3) δ 1.63-1.76 (m, 2H), 1.80-2.05 (m, 2H), 2.10 (s, 6H), 2.43-2.80 (m, 3H), 3.54 (s, 3H), 3.83 (s, 4H), 4.61 (br s, 1H), 4.90 (br s, 1H), 7.04-7.20 (m, 6H), 7.36 (d, 2H, J=7.2 Hz), 8.35 (d, 2H, J=1.2 Hz); 13C NMR (CDCl3) 18.43, 27.22, 28.22, 42.96, 45.27, 55.07, 58.34, 108.42, 110.29, 122.33, 122.36, 122.72, 129.12, 131.10, 133.84, 138.37, 146.25, 154.51, 157.80, 163.72; ES-MS m/z 506 (M+Na). Anal. Calcd. for C28H33N7O.0.9H2O: C, 67.28; H, 7.02; N, 19.62. Found: C, 67.19; H, 6.97; N, 19.50.

Aufarbeitung

  1. concentrationThe solution was concentrated to dryness
  2. additiontreated with saturated aqueous NaHCO3 (30 mL)
  3. extractionextracted with CH2Cl2 (3×15 mL)
  4. dry with materialThe combined organic extracts were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification of the crude material by flash chromatography on silica gel (CH2Cl2/MeOH/NH4OH, 92:4:4)

Quellen und Nachweise

ORD-Eintrag
ord-fbb3d68d94aa42a89a4f6ad2d4c30ee9
Quelldatensatz
uspto-grants-2011_01
Patentnummer
US07863293B2

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