Sodium Hydroxide → N-[4-(8-azabicyclo[3.2.1]oct-8-yl)-3-(trifluoromethyl)benzyl]-N'-1H-indazol-4-ylurea

HRID 586081Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 586081
[CH:1]12[N:8]([C:9]3[CH:32]=[CH:31][C:12]([CH2:13][NH:14][C:15]([NH:17][C:18]4[CH:26]=[CH:25][CH:24]=[C:23]5[C:19]=4[CH:20]=[N:21][N:22]5C(OC)=O)=[O:16])=[CH:11][C:10]=3[C:33]([F:36])([F:35])[F:34])[CH:5]([CH2:6][CH2:7]1)[CH2:4][CH2:3][CH2:2]2.[OH-].[Na+]>CO>[CH:5]12[N:8]([C:9]3[CH:32]=[CH:31][C:12]([CH2:13][NH:14][C:15]([NH:17][C:18]4[CH:26]=[CH:25][CH:24]=[C:23]5[C:19]=4[CH:20]=[N:21][NH:22]5)=[O:16])=[CH:11][C:10]=3[C:33]([F:34])([F:36])[F:35])[CH:1]([CH2:7][CH2:6]1)[CH2:2][CH2:3][CH2:4]2

Komponenten

4

Edukt 2

HCID 14798Sodium HydroxideHCID 22337659methyl 4-[({[4-(8-azabicyclo[3.2.1]oct-8-yl)-3-(trifluoromethyl)benzyl]amino}carbonyl)amino]-1H-indazole-1-carboxylate

Produkt 1

HCID 22337696N-[4-(8-azabicyclo[3.2.1]oct-8-yl)-3-(trifluoromethyl)benzyl]-N'-1H-indazol-4-ylurea

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel2×

Versuchsvorschrift

A suspension of methyl 4-[({[4-(8-azabicyclo[3.2.1]oct-8-yl)-3-(trifluoromethyl)benzyl]amino}carbonyl)amino]-1H-indazole-1-carboxylate (1.65 g, 3.29 mmol) in methanol (30 mL) was treated with 1.2 N NaOH in MeOH (10 mL). The mixture was stirred for 30 minutes and concentrated under reduced pressure. The residue was partitioned between ethyl acetate and saturated NaHCO3 solution. The separated aqueous phase was extracted with ethyl acetate and the combined organic layers were washed with brine, dried (Na2SO4), filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography (7% to 10% MeOH/CH2Cl2) to provide the title compound as a solid. The obtained solid was treated with ethanolic HCl followed by precipitation with diethyl ether to provide the hydrochloride salt. 1H NMR (300 MHz, DMSO-d6) δ 8.99 (s, 1H), 8.19 (s, 1H), 7.62 (d, 1H, J=7.5 Hz), 7.57 (d, 1H, J=2.0 Hz), 7.46 (dd, 1H, J=8.5, 2.0 Hz), 7.19 (t, 1H, J=8.1 Hz), 7.10 (m, 3H), 4.31 (m, 2H), 3.72 (m, 2H), 1.93 (m, 2H), 1.87-1.56 (m, 5H), 1.48 (m, 3H); MS (ESI) 444 (M+H)+; Anal. Calcd for C23H24F3N5O.1.6HCl: C, 55.05; H, 5.14; N, 13.96. Found: C, 54.95; H, 4.66; N, 13.53.

Aufarbeitung

  1. concentrationconcentrated under reduced pressure
  2. customThe residue was partitioned between ethyl acetate and saturated NaHCO3 solution
  3. extractionThe separated aqueous phase was extracted with ethyl acetate
  4. washthe combined organic layers were washed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customThe residue was purified by flash chromatography (7% to 10% MeOH/CH2Cl2)

Quellen und Nachweise

ORD-Eintrag
ord-b184f81289be457baa19f55171c8e73b
Quelldatensatz
uspto-grants-2005_08
Patentnummer
US06933311B2

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