Acetic Acid → HCID 57406016, Verbindung

HRID 1520050

Reaktionsgleichung

Reaktionsgleichung von HRID 1520050
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O[C:20]([N:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1)=O)(C)(C)C.[CH3:28][C:29]1[CH:30]=[C:31]2[C:35](=[CH:36][CH:37]=1)[NH:34][N:33]=[C:32]2[C:38]1[N:39]=[N:40][N:41]([C:43]2[CH:50]=[CH:49][C:46](C=O)=[CH:45][CH:44]=2)[CH:42]=1.C(O)(=O)C.C([BH3-])#N.[Na+]>CC(N(C)C)=O>[CH3:28][C:29]1[CH:30]=[C:31]2[C:35](=[CH:36][CH:37]=1)[NH:34][N:33]=[C:32]2[C:38]1[N:39]=[N:40][N:41]([C:43]2[CH:44]=[CH:45][C:46]([CH2:20][N:22]3[CH2:23][CH2:24][NH:25][CH2:26][CH2:27]3)=[CH:49][CH:50]=2)[CH:42]=1

Komponenten

7

Edukt 5

HCID 176Acetic AcidHCID 143452tert-Butyl piperazine-1-carboxylateHCID 5003444Sodium cyanoborohydrideHCID 5049666Sodium triacetoxyborohydride2×HCID 715340964-[4-(5-methyl-1H-indazol-3-yl)-1H-1,2,3-triazol-1-yl]benzaldehyde

Produkt 1

HCID 57406016HCID 57406016, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 31374DimethylacetamideLösungsmittel

Versuchsvorschrift

Sodium triacetoxyborohydride (279 mg; 1.32 mmol; 2.0 eq.) was added to a solution of tert-butyl-1-piperazinecarboxylate (1.22 g; 6.59 mmol; 10 eq.) and 4-[4-(5-methyl-1H-indazol-3-yl)-1H-1,2,3-triazol-1-yl]benzaldehyde (200 mg; 0.66 mmol; 1.0 eq.) in DMA (4 mL) and the reaction mixture was stirred overnight at RT. Sodium triacetoxyborohydride (279 mg; 1.32 mmol; 2.0 eq.) and glacial acetic acid (75.42 μl; 1.32 mmol; 2.00 eq.) then sodium cyanoborohydride (83 mg; 1.32 mmol; 2. eq.) were added to complete the reaction which was quenched with water and extracted with EtOAc (twice). Combined organic phases were washed with brine, dried over magnesium sulfate, filtered and concentrated. The resulting gum was stirred at RT in a solution of HCl in dioxane (5 mL, 4N) for 2 hours. The reaction mixture was basified to pH=9-10 and extracted with EtOAc. Organic layer was dried over magnesium sulfate, filtered and concentrated. Purification by preparative HPLC afforded the title compound as a formic acid salt. It was dissolved in MeOH and passed through a SPE-NH2 cartridge. The fractions containing the desired compound were concentrated to dryness affording a yellow gum, which was twice sonicated in 3 mL of Et2O. The suspension obtained was concentrated then dried overnight under high vacuum to afford the title compound as a beige solid. 1H NMR (300 Mz, DMSO-d6) δ: 13.23 (brs, 1H), 9.25 (s, 1H), 8.14-8.13 (m, 1H), 8.00 (d, J=8.5 Hz, 2H), 7.54 (d, J=8.5 Hz, 2H), 7.50 (d, J=8.5 Hz, 1H), 7.28 (dd, J=8.5 Hz, 1.5 Hz, 1H), 3.52 (s, 2H), 2.72-2.69 (m, 4H), 2.487 (s, 3H), 2.32-2.30 (m, 4H). HPLC (Condition A): Rt 2.22 min (purity 95.4%). MS (ESI+): 374.3, MS (ESI−): 372.3.

Aufarbeitung

  1. customthe reaction which
  2. customwas quenched with water
  3. extractionextracted with EtOAc (twice)
  4. washCombined organic phases were washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. stirringThe resulting gum was stirred at RT in a solution of HCl in dioxane (5 mL, 4N) for 2 hours
  9. extractionextracted with EtOAc
  10. dry with materialOrganic layer was dried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customPurification by preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-d42b143345654b8ca8a8c7a48df8541d
Quelldatensatz
uspto-grants-2015_07
Patentnummer
US09073892B2

Verknüpfte Notizen

Wird geladen…