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

HRID 251188

Reaktionsgleichung

Reaktionsgleichung von HRID 251188
[C:1](N1C=CN=C1)(N1C=CN=C1)=[O:2].S(O)(O)(=O)=O.[NH2:18][C:19]1[NH:20][CH:21]=[CH:22][N:23]=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>C(Cl)Cl.CN(C=O)C>[NH:20]1[CH:21]=[CH:22][N:23]=[C:19]1[NH:18][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

7

Edukt 4

HCID 682631,1'-CarbonyldiimidazoleHCID 81531Diisopropylethylamine2×HCID 135136Bis(2-amino-1H-imidazole) sulphateHCID 58996965Bis-(3-methyl-pyridin-2-ylmethyl)-piperidin-4-yl-amine

Produkt 1

HCID 589971064-[bis-(3-methyl-pyridin-2-ylmethyl)-amino]-piperidine-1-carboxylic acid (1H-imidazol-2-yl)-amideAusbeute 17 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

A solution of 1,1′-carbonyldiimidazole (0.0924 g, 0.57 mmol), 2-aminoimidazole sulfate (0.0687 g, 0.52 mmol), and DIPEA (0.36 mL, 2.08 mmol) in CH2Cl2 (6 mL) and DMF (6 mL) was stirred at room temperature for 4.5 hours. The mixture was concentrated to rid of CH2Cl2, and DIPEA (0.36 mL, 2.08 mmol) and COMPOUND 249 (0.1614 g, 0.52 mmol) were added. The mixture stirred at 60° C. for 19 hours, then concentrated. Saturated NaHCO3 (15 mL) was added and extracted with CH2Cl2 (3×30 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated. Purification of the crude material by column chromatography on silica gel (50:1:1 CH2Cl2-MeOH—NH4OH) provided 37.1 mg (16%) COMPOUND 345 as a white solid. 1H NMR (CDCl3) δ 1.66-1.70 (m, 2H), 1.93-1.97 (m, 2H), 2.08 (s, 6H), 2.72 (t, 3H, J=10.8 Hz), 3.82 (s, 4H), 4.32 (d, 2H, J=11.4 Hz), 6.70 (s, 2H), 7.07-7.09 (m, 2H), 7.36 (d, 2H, J=7.2 Hz), 8.34 (s, 2H). 13C NMR (CDCl3) 18.37, 27.61, 44.75, 54.96, 57.81, 122.81, 133.79, 138.43, 145.43, 146.30, 155.71, 157.54. ES-MS m/z 420.1 (M+H). Anal. Calcd. for C23H29N7O.0.3CH2Cl2: C, 62.89; H, 6.70; N, 22.03. Found: C, 62.84; H, 6.93; N, 21.82.

Aufarbeitung

  1. concentrationThe mixture was concentrated
  2. additionwere added
  3. concentrationconcentrated
  4. additionSaturated NaHCO3 (15 mL) was added
  5. extractionextracted with CH2Cl2 (3×30 mL)
  6. dry with materialThe combined organic extracts were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification of the crude material by column chromatography on silica gel (50:1:1 CH2Cl2-MeOH—NH4OH)

Quellen und Nachweise

ORD-Eintrag
ord-a824a137c40b4ec7a5f214a3e3529515
Quelldatensatz
uspto-grants-2011_01
Patentnummer
US07863293B2

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