Pyridine → 3-[4-(azetidin-1-ylcarbonyl)-2-chlorophenoxy]-5-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethoxy)-N-pyrazin-2-ylbenzamide

HRID 20604

Reaktionsgleichung

Reaktionsgleichung von HRID 20604
ClC(N(C)C)=C(C)C.[N:9]1([C:13]([C:15]2[CH:42]=[CH:41][C:18]([O:19][C:20]3[CH:21]=[C:22]([CH:26]=[C:27]([O:29][C@@H:30]([CH3:40])[CH2:31][O:32][Si:33]([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:35])[CH3:34])[CH:28]=3)[C:23](O)=[O:24])=[C:17]([Cl:43])[CH:16]=2)=[O:14])[CH2:12][CH2:11][CH2:10]1.[NH2:44][C:45]1[CH:50]=[N:49][C:48](C)=[CH:47][N:46]=1.N1C=CC=CC=1>C(Cl)Cl>[N:9]1([C:13]([C:15]2[CH:42]=[CH:41][C:18]([O:19][C:20]3[CH:21]=[C:22]([CH:26]=[C:27]([O:29][C@@H:30]([CH3:40])[CH2:31][O:32][Si:33]([C:36]([CH3:37])([CH3:38])[CH3:39])([CH3:35])[CH3:34])[CH:28]=3)[C:23]([NH:44][C:45]3[CH:50]=[N:49][CH:48]=[CH:47][N:46]=3)=[O:24])=[C:17]([Cl:43])[CH:16]=2)=[O:14])[CH2:10][CH2:11][CH2:12]1

Komponenten

6

Edukt 4

HCID 1049PyridineHCID 3132155-Methylpyrazin-2-amineHCID 6407921-Chloro-N,N-2-trimethylpropenylamineHCID 593469103-[4-(Azetidin-1-ylcarbonyl)-2-chlorophenoxy]-5-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethoxy)benzoic acid

Produkt 1

HCID 593469193-[4-(azetidin-1-ylcarbonyl)-2-chlorophenoxy]-5-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethoxy)-N-pyrazin-2-ylbenzamideAusbeute 12,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

1-Chloro-N,N,2-trimethyl-1-propenylamine (0.073 mL, 0.55 mmol) was added to a solution of 3-[4-(azetidin-1-ylcarbonyl)-2-chlorophenoxy]-5-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethoxy)benzoic acid (260 mg, 0.5 mmol) in DCM (10 mL) and stirred at RT for 1 hour. 2-Amino-5-methylpyrazine (95 mg, 1 mmol) and pyridine (0.081 mL, 1.0 mmol) were added and the reaction stirred for a further 30 mins. The solvent was removed in vacuo. Water (10 mL) was added and the mixture extracted with ethyl acetate (2×10 mL). The extracts were combined and washed with 1N citric acid, water (10 mL) and brine (10 mL), dried (MgSO4), filtered, and evaporated in vacuo to give the crude product which was chromatographed on silica, eluting with a gradient of 50-100% ethyl acetate in isohexane, to give the desired compound (37 mg).

Aufarbeitung

  1. stirringthe reaction stirred for a further 30 mins
  2. customThe solvent was removed in vacuo
  3. additionWater (10 mL) was added
  4. extractionthe mixture extracted with ethyl acetate (2×10 mL)
  5. washwashed with 1N citric acid, water (10 mL) and brine (10 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customto give the crude product which
  10. customwas chromatographed on silica
  11. washeluting with a gradient of 50-100% ethyl acetate in isohexane

Quellen und Nachweise

ORD-Eintrag
ord-1074c8a6c1f44ccba7847b5fb8d95594
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07745475B2

Verknüpfte Notizen

Wird geladen…