Sodium Hydroxide → 8-{4-[4-(1-Benzenesulfonyl-1H-indol-5-ylamino)-quinazolin-6-yl]-benzyl}-8-aza-bicyclo[3.2.1]octan-3-ol

HRID 991469Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 991469
[CH:1]12[NH:8][CH:5]([CH2:6][CH2:7]1)[CH2:4][CH:3]([OH:9])[CH2:2]2.[C:10]1([S:16]([N:19]2[C:27]3[C:22](=[CH:23][C:24]([NH:28][C:29]4[C:38]5[C:33](=[CH:34][CH:35]=[C:36]([C:39]6[CH:46]=[CH:45][C:42]([CH:43]=O)=[CH:41][CH:40]=6)[CH:37]=5)[N:32]=[CH:31][N:30]=4)=[CH:25][CH:26]=3)[CH:21]=[CH:20]2)(=[O:18])=[O:17])[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[BH3-]C#N.[Na+].[OH-].[Na+]>C(Cl)Cl.CC(O)=O.CO.C(Cl)(Cl)Cl>[C:10]1([S:16]([N:19]2[C:27]3[C:22](=[CH:23][C:24]([NH:28][C:29]4[C:38]5[C:33](=[CH:34][CH:35]=[C:36]([C:39]6[CH:40]=[CH:41][C:42]([CH2:43][N:8]7[CH:5]8[CH2:6][CH2:7][CH:1]7[CH2:2][CH:3]([OH:9])[CH2:4]8)=[CH:45][CH:46]=6)[CH:37]=5)[N:32]=[CH:31][N:30]=4)=[CH:25][CH:26]=3)[CH:21]=[CH:20]2)(=[O:17])=[O:18])[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Komponenten

9

Edukt 4

HCID 14798Sodium HydroxideHCID 681478-Azabicyclo[3.2.1]octan-3-olHCID 5003444Sodium cyanoborohydrideHCID 116706224-[4-(1-Benzenesulfonyl-1H-indol-5-ylamino)-quinazolin-6-yl]-benzaldehyde

Produkt 1

HCID 98519638-{4-[4-(1-Benzenesulfonyl-1H-indol-5-ylamino)-quinazolin-6-yl]-benzyl}-8-aza-bicyclo[3.2.1]octan-3-olAusbeute 36,9 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 176Acetic AcidLösungsmittelHCID 887MethanolLösungsmittelHCID 6212ChloroformLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of CHCl3 (1.5 mL) and MeOH (3 mL) in a round-bottom flask under N2 was added 8-aza-bicyclo[3.2.1]octan-3-ol 24 (70 mg, 0.495 mmol). AcOH was added to adjust the pH to 5. To the amine solution was added 4-[4-(1-benzenesulfonyl-1H-indol-5-ylamino)-quinazolin-6-yl]-benzaldehyde 22 (100 mg, 0.198 mmol) and the resulting solution was stirred at room temperature for 3 hours. NaCNBH3 was added to the reaction mixture which was then allowed to stir overnight at room temperature under an atmosphere of N2. The solution was diluted with CH2Cl2 and poured into 1N NaOH (10 mL). The aqueous layer was separated and extracted with another 2×15 mL of CH2Cl2. The organic layers were dried (MgSO4) and the solvent was removed under reduced pressure to provide a yellow viscous oil. The residue was purified by flash chromatography (silica gel, CH2Cl2-10%MeOH/CH2Cl2) to provide 45 mg of compound 23 as a white solid in 36% yield. HPLC, rt=5.25 min; MS (Cl) m/e 616.2 (M++1, 100).

Aufarbeitung

  1. stirringto stir overnight at room temperature under an atmosphere of N2
  2. customThe aqueous layer was separated
  3. extractionextracted with another 2×15 mL of CH2Cl2
  4. dry with materialThe organic layers were dried (MgSO4)
  5. customthe solvent was removed under reduced pressure
  6. customto provide a yellow viscous oil
  7. customThe residue was purified by flash chromatography (silica gel, CH2Cl2-10%MeOH/CH2Cl2)

Quellen und Nachweise

ORD-Eintrag
ord-6fc0de08823a4388a6b3a17c0dcbebd9
Quelldatensatz
uspto-grants-2002_10
Patentnummer
US06465449B1

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