(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protected → tert-butyl (1S,2R)-2-(6-carbamoyl-5-(6-ethoxypyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate

HRID 1396431Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1396431
Cl[C:2]1[N:7]=[N:6][C:5]([C:8]([NH2:10])=[O:9])=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH2:19][CH3:20])[N:13]=2)[CH:3]=1.[NH2:21][C@@H:22]1[CH2:27][CH2:26][CH2:25][CH2:24][C@@H:23]1[NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32]>CN1C(=O)CCC1>[C:8]([C:5]1[N:6]=[N:7][C:2]([NH:21][C@@H:22]2[CH2:27][CH2:26][CH2:25][CH2:24][C@@H:23]2[NH:28][C:29](=[O:35])[O:30][C:31]([CH3:33])([CH3:32])[CH3:34])=[CH:3][C:4]=1[NH:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH2:19][CH3:20])[N:13]=1)(=[O:9])[NH2:10]

Komponenten

4

Edukt 2

HCID 1514389(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protected2×HCID 866897756-Chloro-4-(6-ethoxypyridin-2-ylamino)pyridazine-3-carboxamide

Produkt 1

HCID 86689776tert-butyl (1S,2R)-2-(6-carbamoyl-5-(6-ethoxypyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamateAusbeute 46 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 13387N-methyl-2-pyrrolidoneLösungsmittel

Reaktionsbedingungen

Temperatur
140 °C

Versuchsvorschrift

6-Chloro-4-(6-ethoxypyridin-2-ylamino)pyridazine-3-carboxamide (33 mg, 112 μmol) and tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (50 mg, 233 μmol) were combined in NMP (2 mL) and stirred at 140° C. for 48 h. A second portion of tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (50 mg, 233 μmol) was added and the reaction was stirred at 140° C. for 96 h, then cooled to room temperature and concentrated in vacuo. The residue obtained was partitioned between water and EtOAc. The aqueous layer was extracted with EtOAc and the organics were combined and washed with brine. The solvent was removed in vacuo to give an orange foam. The foam was concentrated onto silica and purified by chromatography (4 g RediSep Gold, 0 to 5% of a mixture of MeOH containing 0.5% NH4OH in dichloromethane, 20 min) to give tert-butyl (1S,2R)-2-(6-carbamoyl-5-(6-ethoxypyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate (32.3 mg, 51.4 μmol, 46%) containing some dichloromethane impurity. This was used directly without further purification. MS (EI/CI) m/z: 372.3 [M+H].

Aufarbeitung

  1. stirringthe reaction was stirred at 140° C. for 96 h
  2. temperaturecooled to room temperature
  3. concentrationconcentrated in vacuo
  4. customThe residue obtained
  5. customwas partitioned between water and EtOAc
  6. extractionThe aqueous layer was extracted with EtOAc
  7. washwashed with brine
  8. customThe solvent was removed in vacuo
  9. customto give an orange foam
  10. concentrationThe foam was concentrated onto silica
  11. custompurified by chromatography (4 g RediSep Gold, 0 to 5% of a mixture of MeOH containing 0.5% NH4OH in dichloromethane, 20 min)

Quellen und Nachweise

ORD-Eintrag
ord-65d1b1de0a2a4cbf8cb97f3074410d48
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08901124B2

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