Hydrochloric Acid → HCID 178502473, Verbindung

HRID 1751615Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1751615
Cl.O1CCOCC1.[Br:8][C:9]1[CH:10]=[C:11]2[C:33](=[CH:34][CH:35]=1)[C:15]1[NH:16][C:17]([C@@H:19]3[C@H:24]4[CH2:25][C@H:21]([CH2:22][CH2:23]4)[N:20]3C(OC(C)(C)C)=O)=[N:18][C:14]=1[CH:13]=[CH:12]2.[CH3:36][O:37][C:38]([NH:40][C@@H:41]([CH:45]([CH3:47])[CH3:46])[C:42](O)=[O:43])=[O:39].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl.CO>[Br:8][C:9]1[CH:10]=[C:11]2[C:33](=[CH:34][CH:35]=1)[C:15]1[NH:16][C:17]([C@@H:19]3[C@H:24]4[CH2:25][C@H:21]([CH2:22][CH2:23]4)[N:20]3[C:42](=[O:43])[C@@H:41]([NH:40][C:38](=[O:39])[O:37][CH3:36])[CH:45]([CH3:47])[CH3:46])=[N:18][C:14]=1[CH:13]=[CH:12]2

Komponenten

9

Edukt 6

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10942966(2S)-2-((methoxycarbonyl)amino)-3-methylbutanoic acidHCID 178452510HCID 178452510, Verbindung

Produkt 1

HCID 178502473HCID 178502473, VerbindungAusbeute 99 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 6344DichloromethaneLösungsmittel3×

Versuchsvorschrift

Hydrogen chloride in dioxane solution (4N, 6.78 mL, 27.18 mmol) was added to (1S,3S,4R)-tert-butyl 3-(7-bromo-1H-naphtho[1,2-d]imidazol-2-yl)-2-azabicyclo[2.2.1]heptane-2-carboxylate (0.80 g, 1.81 mmol) in methylene chloride:methanol (18.1 mL: 3.6 mL). The suspension was allowed to stir at room temperature for one hour. Upon completion by LCMS, the reaction was concentrated to dryness and the crude product (assumed 1.81 mmol) was suspended in methylene chloride (18 mL). (S)-2-(methoxycarbonylamino)-3-methylbutanoic acid (0.38 g, 2.17 mmol) and DIPEA (1.58 mL, 9.04 mmol) were added to the slurry. HATU (1.03 g, 2.71 mmol) was added and the reaction was stirred at room temperature for 3 hours. Upon completion, the crude reaction was diluted in methylene chloride and washed with 1N HCl, and aqueous sodium bicarbonate. The organic layer was concentrated and purified by normal phase chromatography (40-80% ethyl acetate (5% methanol) in hexanes) to give methyl (S)-1-((1S,3S,4R)-3-(7-bromo-1H-naphtho[1,2-d]imidazol-2-yl)-2-azabicyclo[2.2.1]heptan-2-yl)-3-methyl-1-oxobutan-2-ylcarbamate (0.949, >99%).

Aufarbeitung

  1. concentrationUpon completion by LCMS, the reaction was concentrated to dryness
  2. stirringthe reaction was stirred at room temperature for 3 hours
  3. customUpon completion, the crude reaction
  4. washwashed with 1N HCl, and aqueous sodium bicarbonate
  5. concentrationThe organic layer was concentrated
  6. custompurified by normal phase chromatography (40-80% ethyl acetate (5% methanol) in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-75cfc73e60a549e684ebcc8437553a89
Quelldatensatz
uspto-grants-2015_10
Patentnummer
US09156823B2

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