Sodium hydride → methyl 1-methyl-3-((8-methyl-8-azabicyclo[3.2.1]octan-3-ylamino)methyl)-1H-indazole-4-carboxylate

HRID 1644277Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1644277
[H-].[Na+].Cl.Cl.[CH3:5][N:6]1[CH:11]2[CH2:12][CH2:13][CH:7]1[CH2:8][CH:9]([NH2:14])[CH2:10]2.[CH:15]([C:17]1[C:25]2[C:24]([C:26]([O:28][CH3:29])=[O:27])=[CH:23][CH:22]=[CH:21][C:20]=2[N:19]([CH3:30])[N:18]=1)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(O)(=O)C.ClCCl>[CH3:30][N:19]1[C:20]2[CH:21]=[CH:22][CH:23]=[C:24]([C:26]([O:28][CH3:29])=[O:27])[C:25]=2[C:17]([CH2:15][NH:14][CH:9]2[CH2:8][CH:7]3[N:6]([CH3:5])[CH:11]([CH2:12][CH2:13]3)[CH2:10]2)=[N:18]1

Komponenten

7

Edukt 4

HCID 24758Sodium hydrideHCID 27759288-methyl-8-azabicyclo[3.2.1]octan-3-amine DihydrochlorideHCID 5049666Sodium triacetoxyborohydrideHCID 86636563HCID 86636563, Verbindung

Produkt 1

HCID 66772681methyl 1-methyl-3-((8-methyl-8-azabicyclo[3.2.1]octan-3-ylamino)methyl)-1H-indazole-4-carboxylateAusbeute 100 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 176Acetic AcidLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

Sodium hydride (60%) (0.19 g) was added in portions to a solution of 8-methyl-8-azabicyclo[3.2.1]octan-3-amine dihydrochloride and stirred at ambient temperature for 1 h. To the reaction mixture, methyl 3-formyl-1-methyl-1H-indazole-4-carboxylate (0.41 g, 1.9 mmol) from Step A of Example 6 in 1% acetic acid in dichloromethane (50 mL) was added and stirred at ambient temperature for 3 h. Sodium triacetoxyborohydride (1.2 g, 5.6 mmol) was added, and the resulting suspension was stirred for 16 h at ambient temperature. The solvent was removed under reduced pressure, and the crude material purified by column chromatography (silica gel, 10:1:0.1 dichloromethane/methanol/concentrated ammonium hydroxide) to afford methyl 1-methyl-3-((8-methyl-8-azabicyclo[3.2.1]octan-3-ylamino)methyl)-1H-indazole-4-carboxylate (0.54 g, 100%) as a yellow oil: 1H NMR (300 MHz, CDCl3) δ 7.75 (d, J=7.5 Hz, 1H), 7.53 (d, J=8.5 Hz, 1H), 7.38 (t, J=6.0 Hz, 1H), 5.49 (s, 1H), 4.26 (s, 2H), 4.04 (s, 3H), 3.96 (s, 3H), 2.99-2.89 (m, 1H), 2.45 (s, 3H), 2.10-1.85 (m, 6H), 1.74-1.62 (m, 4H); LC/MS (ESI+) m/z 343 (M+H).

Aufarbeitung

  1. stirringstirred at ambient temperature for 3 h
  2. stirringthe resulting suspension was stirred for 16 h at ambient temperature
  3. customThe solvent was removed under reduced pressure
  4. customthe crude material purified by column chromatography (silica gel, 10:1:0.1 dichloromethane/methanol/concentrated ammonium hydroxide)

Quellen und Nachweise

ORD-Eintrag
ord-20f4f30c6681451db5bd6092e5ca6fb5
Quelldatensatz
uspto-grants-2012_02
Patentnummer
US08124600B2

Notizen zur Reaktion

Wird geladen…