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

HRID 1396422
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1396422
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]=[C:16]([CH3:18])[CH:15]=[C:14]([CH3:19])[CH:13]=2)[CH:3]=1.[NH2:20][C@@H:21]1[CH2:26][CH2:25][CH2:24][CH2:23][C@@H:22]1[NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31]>CN1C(=O)CCC1.C(OCC)(=O)C>[C:8]([C:5]1[N:6]=[N:7][C:2]([NH:20][C@@H:21]2[CH2:26][CH2:25][CH2:24][CH2:23][C@@H:22]2[NH:27][C:28](=[O:34])[O:29][C:30]([CH3:32])([CH3:31])[CH3:33])=[CH:3][C:4]=1[NH:11][C:12]1[CH:17]=[C:16]([CH3:18])[CH:15]=[C:14]([CH3:19])[CH:13]=1)(=[O:9])[NH2:10]
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

5

Edukt 2

HCID 1514389(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protected3×HCID 73777170HCID 73777170, Verbindung

Produkt 1

HCID 86689771tert-butyl (1S,2R)-2-(6-carbamoyl-5-(3,5-dimethylphenylamino)pyridazin-3-ylamino)cyclohexylcarbamateAusbeute 42 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8857Ethyl AcetateLösungsmittel
HCID 13387
N-methyl-2-pyrrolidone
Lösungsmittel

Reaktionsbedingungen

Temperatur
140 °C

Versuchsvorschrift

To a solution of 6-chloro-4-(3,5-dimethylphenylamino)pyridazine-3-carboxamide (44 mg, 159 μmol) in NMP (530 μL) was added tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (68.2 mg, 318 μmol) and the mixture heated to 140° C. for 20 h. Additional tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (68.2 mg, 318 μmol) was then added and heating continued for a further 7 h. Finally, another portion of tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (34.1 mg, 159 μmol) was added and the mixture heated for 16 h. The reaction mixture was cooled, and then diluted with ethyl acetate. The phases were separated and the organic phase then washed with water and brine. The organic phase was collected, concentrated in vacuo, and the residue obtained was purified by chromatography (silica, 30 to 70% ethyl acetate in hexanes) to give tert-butyl (1S,2R)-2-(6-carbamoyl-5-(3,5-dimethylphenylamino)pyridazin-3-ylamino)cyclohexylcarbamate (30 mg, 66.0 μmol, 42%) as a brown oil. MS (EI/CI) m/z: 455.2 [M+H].

Aufarbeitung

  1. temperatureheating
  2. temperaturethe mixture heated for 16 h
  3. temperatureThe reaction mixture was cooled
  4. customThe phases were separated
  5. washthe organic phase then washed with water and brine
  6. customThe organic phase was collected
  7. concentrationconcentrated in vacuo
  8. customthe residue obtained
  9. customwas purified by chromatography (silica, 30 to 70% ethyl acetate in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-a8d84a34310e4717a1eac7a61825a30c
Quelldatensatz
uspto-grants-2014_12
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08901124B2

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