Hydrochloric Acid → 3-[4-amino-5-(2-benzyl-2H-indazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-7-yl]piperidin-3-ol

HRID 1972924Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1972924
[NH2:1][C:2]1[C:7]2=[C:8]([C:25]3[CH:26]=[CH:27][C:28]4[C:32]([CH:33]=3)=[N:31][N:30]([CH2:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[CH:29]=4)[CH:9]=[C:10]([C:11]3([OH:24])[CH2:16][CH2:15][CH2:14][N:13](C(OC(C)(C)C)=O)[CH2:12]3)[N:6]2[N:5]=[CH:4][N:3]=1.Cl>CO.O1CCOCC1>[NH2:1][C:2]1[C:7]2=[C:8]([C:25]3[CH:26]=[CH:27][C:28]4[C:32]([CH:33]=3)=[N:31][N:30]([CH2:34][C:35]3[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=3)[CH:29]=4)[CH:9]=[C:10]([C:11]3([OH:24])[CH2:16][CH2:15][CH2:14][NH:13][CH2:12]3)[N:6]2[N:5]=[CH:4][N:3]=1

Komponenten

5

Edukt 2

HCID 313Hydrochloric AcidHCID 58529683tert-butyl 3-[4-amino-5-(2-benzyl-2H-indazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-7-yl]-3-hydroxypiperidine-1-carboxylate

Produkt 1

HCID 585294413-[4-amino-5-(2-benzyl-2H-indazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-7-yl]piperidin-3-olAusbeute 96 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

To a solution of tert-butyl 3-[4-amino-5-(2-benzyl-2H-indazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-7-yl]-3-hydroxypiperidine-1-carboxylate (270 mg, 0.500 mmol) in MeOH (2.5 mL) was added 4M HCl in dioxane (1.25 mL). The mixture was stirred at rt for 17 h. The mixture was concentrated and the residue was dissolved in 3:1 CHCl3/isopropanol (25 mL). The mixture was washed with saturated, aqueous NaHCO3 (25 mL), brine, dried (Na2SO4) and concentrated to dryness to afford 211 mg (96%) of the desired product, which was approximately 50% pure. ES-MS m/z 440.19 [M+H]+, HPLC RT (min) 1.97. 50 mg of material was purified by preparative HPLC using a gradient elution from 15% to 40% acetonitrile in water followed by filtration through an acidic resin, washing with MeOH. The product was eluted with 2M NH3 in MeOH and the filtrate was concentrated to provide 28 mg of pure desired product. 1H NMR (400 MHz, DMSO-d6) δ 8.54 (s, 1 H), 7.89 (s, 1 H), 7.80 (d, 1 H), 7.58 (s, 1 H), 7.27-7.37 (m, 5 H), 7.13 (dd, 1.36 Hz, 1 H), 6.69 (s, 1 H), 5.64 (s, 2 H), 5.19 (s, 1 H), 2.77-2.93 (m, 2 H), 2.43-2.54 (m, 3 H), 2.12 (br s, 1 H), 1.68-1.88 (m, 2 H), 1.33-1.46 (m, 1 H); ES-MS m/z 439.92 [M+H]+, HPLC RT (min) 2.06.

Aufarbeitung

  1. concentrationThe mixture was concentrated
  2. dissolutionthe residue was dissolved in 3:1 CHCl3/isopropanol (25 mL)
  3. washThe mixture was washed with saturated, aqueous NaHCO3 (25 mL), brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated to dryness

Quellen und Nachweise

ORD-Eintrag
ord-d2c38a7a88ff4f4a95136478d7eb66cb
Quelldatensatz
uspto-grants-2013_04
Patentnummer
US08431695B2

Notizen zur Reaktion

Wird geladen…