4,4'-Diaminodicyclohexylmethane → N-{4-[(4-aminocyclohexyl)methyl]cyclohexyl}-6-chloro-4-(5-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-amine

HRID 2089043

Reaktionsgleichung

Reaktionsgleichung von HRID 2089043
Cl[C:2]1[CH:7]=[C:6]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[C:14]([O:17][CH3:18])[CH:15]=3)[NH:10][CH:9]=2)[CH:5]=[C:4]([Cl:19])[N:3]=1.[CH2:20]([CH:28]1[CH2:33][CH2:32][CH:31]([NH2:34])[CH2:30][CH2:29]1)[CH:21]1[CH2:26][CH2:25][CH:24]([NH2:27])[CH2:23][CH2:22]1>O>[NH2:27][CH:24]1[CH2:23][CH2:22][CH:21]([CH2:20][CH:28]2[CH2:33][CH2:32][CH:31]([NH:34][C:2]3[CH:7]=[C:6]([C:8]4[C:16]5[C:11](=[N:12][CH:13]=[C:14]([O:17][CH3:18])[CH:15]=5)[NH:10][CH:9]=4)[CH:5]=[C:4]([Cl:19])[N:3]=3)[CH2:30][CH2:29]2)[CH2:26][CH2:25]1

Komponenten

4

Edukt 2

HCID 156604,4'-DiaminodicyclohexylmethaneHCID 871921833-(2,6-Dichloro-4-pyridinyl)-5-methoxy-1H-pyrrolo[2,3-b]pyridine

Produkt 1

HCID 87191065N-{4-[(4-aminocyclohexyl)methyl]cyclohexyl}-6-chloro-4-(5-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-amineAusbeute 58,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Versuchsvorschrift

A mixture of Example 149e (0.634 g, 2.16 mmol) and 4,4′-methylenedicyclohexanamine (2.267 g, 10.78 mmol) was heated at 155° C. for 90 minutes and cooled. While still warm, the slurry was treated with water and extracted with EtOAc (2×). The combined organic layers were dried over MgSO4, filtered, concentrated, and purified on a 28 g Biotage KP-NH column using the ISCO Companion flash system eluting with MeOH/EtOAc (3:97 to 5:95) to give 593 mg of the title compound. 55 mg of this material was further purified by reverse-phase HPLC as described in Example 56 to give 17 mg of the title compound as trifluoroacetic acid salts. 1H NMR (400 MHz, CD3OD) ppm 1.02-1.45 (m, 9H), 1.57-1.92 (m, 9H), 1.99-2.18 (m, 2H), 3.02 (m, 1H), 3.70 (m, 1H), 3.95 (s, 3H), 6.72-6.92 (m, 2H), 7.80-7.91 (m, 2H), 8.06 (s, 1H). MS (DCI+) m/z 468.3 (M+H)+.

Aufarbeitung

  1. temperaturecooled
  2. temperatureWhile still warm
  3. extractionextracted with EtOAc (2×)
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified on a 28 g Biotage KP-NH column
  8. washeluting with MeOH/EtOAc (3:97 to 5:95)

Quellen und Nachweise

ORD-Eintrag
ord-fee6dbc9090444cba735461608e3ab1e
Quelldatensatz
uspto-grants-2013_05
Patentnummer
US08435980B2

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