Triethylamine → tert-butyl (1S,2S,4S)-4-(5'-chloro-6-(3-fluorobenzylamino)-2,4'-bipyridin-2'-yl-amino)-2-methylcyclohexylcarbamate tert-butyl (1R,2R,4R)-4-(5'-chloro-6-(3-fluorobenzylamino)-2,4'-bipyridin-2'-yl-amino)-2-methylcyclohexylcarbamate

HRID 1623335Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1623335
[Cl:1][C:2]1[C:3]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([NH:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=3)[N:10]=2)=[CH:4][C:5](F)=[N:6][CH:7]=1.[NH2:24][C@H:25]1[CH2:30][CH2:29][C@H:28]([NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[C@@H:27]([CH3:39])[CH2:26]1.[NH2:40][C@@H:41]1[CH2:46][CH2:45][C@@H:44]([NH:47][C:48](=[O:54])[O:49][C:50]([CH3:53])([CH3:52])[CH3:51])[C@H:43]([CH3:55])[CH2:42]1.C(N(CC)CC)C>CS(C)=O.CCOC(C)=O.C([O-])(O)=O.[Na+]>[Cl:1][C:2]1[C:3]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([NH:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=3)[N:10]=2)=[CH:4][C:5]([NH:24][C@H:25]2[CH2:30][CH2:29][C@H:28]([NH:31][C:32](=[O:38])[O:33][C:34]([CH3:36])([CH3:35])[CH3:37])[C@@H:27]([CH3:39])[CH2:26]2)=[N:6][CH:7]=1.[Cl:1][C:2]1[C:3]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([NH:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=3)[N:10]=2)=[CH:4][C:5]([NH:40][C@@H:41]2[CH2:46][CH2:45][C@@H:44]([NH:47][C:48](=[O:54])[O:49][C:50]([CH3:52])([CH3:51])[CH3:53])[C@H:43]([CH3:55])[CH2:42]2)=[N:6][CH:7]=1

Komponenten

7

Edukt 3

HCID 8471TriethylamineHCID 58127193HCID 58127193, VerbindungHCID 86650623tert-butyl (1S,2S,4S)-4-amino-2-methylcyclohexylcarbamate tert-butyl (1R,2R,4R)-4-amino-2-methylcyclohexylcarbamate

Produkt 1

HCID 86650625tert-butyl (1S,2S,4S)-4-(5'-chloro-6-(3-fluorobenzylamino)-2,4'-bipyridin-2'-yl-amino)-2-methylcyclohexylcarbamate tert-butyl (1R,2R,4R)-4-(5'-chloro-6-(3-fluorobenzylamino)-2,4'-bipyridin-2'-yl-amino)-2-methylcyclohexylcarbamate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 679Dimethyl SulfoxideLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 516892Sodium BicarbonateLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A mixture of Intermediate B (preparation of intermediate B is described in the intermediate session which is in front of the Examples) (25 mg, 0.075 mmol), tert-butyl (1S,2S,4S)-4-amino-2-methylcyclohexylcarbamate/tert-butyl(1R,2R,4R)-4-amino-2-methylcyclohexylcarbamate (25.8 mg, 0.113 mmol), triethylamine (28 μl, 0.201 mmol) in DMSO (0.25 mL) was heated at 100° C. for 3 days. The mixture was allowed to cool to ambient temperature and diluted with EtOAc (20 mL) and saturated aqueous NaHCO3 solution (10 mL). The separated aqueous layer was extracted with EtOAc (3×). The combined organic layers were dried over Na2SO4, filtered off and concentrated in vacuo providing crude tert-butyl (1S,2S,4S)-4-(5′-chloro-6-(3-fluorobenzylamino)-2,4′-bipyridin-2′-yl-amino)-2-methylcyclohexylcarbamate/tert-butyl (1R,2R,4R)-4-(5′-chloro-6-(3-fluorobenzylamino)-2,4′-bipyridin-2′-yl-amino)-2-methylcyclohexylcarbamate, which was directly used in the next step without further purification.

Aufarbeitung

  1. temperatureto cool to ambient temperature
  2. extractionThe separated aqueous layer was extracted with EtOAc (3×)
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. filtrationfiltered off
  5. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-1ac8c8ddc6d34bf98e19e0851fe482f1
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08778951B2

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