Hydrochloric Acid → HCID 118036627, Verbindung

HRID 1778080Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1778080
Cl[C:2]1[C:7]([C:8]#[N:9])=[CH:6][N:5]=[C:4]([NH:10][C:11]([N:13]2[C:22]3[C:17](=[CH:18][CH:19]=[C:20]([CH:23]([O:26]C)OC)[N:21]=3)[CH2:16][CH2:15][CH2:14]2)=[O:12])[CH:3]=1.[CH3:28][N:29]1[CH2:33][CH2:32][C:31]2([CH2:38][CH2:37][NH:36][CH2:35][CH2:34]2)[CH2:30]1.[F-].[K+].C([O-])([O-])=O.[K+].[K+].Cl>CN(C=O)C.CCOC(C)=O>[C:8]([C:7]1[C:2]([N:36]2[CH2:37][CH2:38][C:31]3([CH2:30][N:29]([CH3:28])[CH2:33][CH2:32]3)[CH2:34][CH2:35]2)=[CH:3][C:4]([NH:10][C:11]([N:13]2[C:22]3[C:17](=[CH:18][CH:19]=[C:20]([CH:23]=[O:26])[N:21]=3)[CH2:16][CH2:15][CH2:14]2)=[O:12])=[N:5][CH:6]=1)#[N:9]

Komponenten

8

Edukt 5

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 522689Potassium FluorideHCID 526441212-Methyl-2,8-diazaspiro[4.5]decaneHCID 118036382HCID 118036382, Verbindung2×

Produkt 1

HCID 118036627HCID 118036627, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

N-(4-chloro-5-cyanopyridin-2-yl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide (intermediate 2J, 40 mg, 0.103 mmol) and 2-methyl-2,8-diazaspiro[4.5]decane (31.8 mg, 0.206 mmol) were dissolved in DMF (1 ml) under argon. The mixture was stirred at 100° C. for 2 h. KF (12.0 mg, 0.206 mmol) and K2CO3 (42.8 mg, 0.309 mmol) were added to the reaction mixture and it was stirred at 100° C. for 3 h. Subsequently, the reaction mixture was cooled to room temperature, treated with conc. HCl (200 μl) and stirred for 30 min. The reaction mixture was diluted in EtOAc and washed with sat. aq. NaHCO3 (2×) and brine. The organic layer was dried over Na2SO4, filtered and concentrated under vacuum. The crude material was purified by normal phase chromatography (4 g silica gel cartridge, heptanes/EtOAc 100:0 to 0:100) followed by supercritical fluid chromatography (SFC 1, diethylaminopropyl stationary phase, DEAP column) to give the title compound as a white solid.

Aufarbeitung

  1. stirringwas stirred at 100° C. for 3 h
  2. temperatureSubsequently, the reaction mixture was cooled to room temperature
  3. stirringstirred for 30 min
  4. washwashed with sat. aq. NaHCO3 (2×) and brine
  5. dry with materialThe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customThe crude material was purified by normal phase chromatography (4 g silica gel cartridge, heptanes/EtOAc 100:0 to 0:100)

Quellen und Nachweise

ORD-Eintrag
ord-35e2f3cd57a949db86d46e101bbd24fa
Quelldatensatz
uspto-grants-2016_02
Patentnummer
US09266883B2

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