Hydrochloric Acid → AZD 8329

HRID 552615Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 552615
Cl.O.[NH:3]([C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=[O:10])=[CH:7][CH:6]=1)[NH2:4].[CH:14]12[CH2:23][CH:18]3[CH2:19][CH:20]([CH2:22][CH:16]([CH2:17]3)[CH:15]1[NH:24][C:25](=[O:37])[C:26](=[CH:33]N(C)C)[C:27](=O)[C:28]([CH3:31])([CH3:30])[CH3:29])[CH2:21]2>CO>[CH:16]12[CH2:22][CH:20]3[CH2:19][CH:18]([CH2:23][CH:14]([CH2:21]3)[CH:15]1[NH:24][C:25]([C:26]1[CH:33]=[N:4][N:3]([C:5]3[CH:6]=[CH:7][C:8]([C:9]([OH:11])=[O:10])=[CH:12][CH:13]=3)[C:27]=1[C:28]([CH3:31])([CH3:30])[CH3:29])=[O:37])[CH2:17]2

Komponenten

6

Edukt 4

HCID 313Hydrochloric Acid2×HCID 962Water2×HCID 120894-Hydrazinobenzoic acidHCID 72312260HCID 72312260, Verbindung2×

Produkt 1

HCID 25006684AZD 8329Ausbeute 74,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel2×

Reaktionsbedingungen

Temperatur
22.5 °C

Versuchsvorschrift

Hydrochloric acid (34.5% w/w, 15.88 g, 5.48 g @100.0%, 0.1504 mole, 1.0 mol. eq) and water (70 ml, 1.4 rel. vol) were added to a suspension of 4-hydrazinobenzoic acid (23.35 g, 22.88 g @100.0%, 0.1504 mole, 1.0 mol. eq) in methanol (1250 ml, 12.5 rel. vol). The resulting suspension was stirred for 30 min at 20 to 25° C. and a solution of N-(2-adamantyl)-2-(dimethylaminomethylidene)-4,4-dimethyl-3-oxo-pentanamide (intermediate #4) (53.47 g, 50.0 g @100.0%, 0.150 in 4 mole, 1.0 mol. eq) at 20-25° C. in methanol (250 ml, 5.0 rel. vol)] added over a period of 20 minutes followed by hydrochloric acid (34.5% w/w, 2.38 g, 0.82 g @100.0%, 0.02264 mole, 0.15 mol. eq) and water (70.0 ml, 1.4 rel. vol). The reaction mass temperature was increased to 62-65° C. and maintained for 90.0 min. For work up methanol solution was concentrated atmospherically until the residual volume 6.0 rel. vol (300.0 ml) remained. The resulting suspension was cooled to 20-25° C. and stirred for 1.0 hr. The product was filtered and washed with ethyl acetate (200.0 ml, 4.0 rel. vol) and sucked dry for 30 min. The product was dried under vacuum (100 mbar) at 50° C. for 8 hrs to give crude 4-[4-(2-adamantylcarbamoyl)-5-tert-butyl-pyrazol-1-yl]benzoic acid (47.0 g, 73.0%).

Aufarbeitung

  1. temperatureThe reaction mass temperature was increased to 62-65° C.
  2. temperaturemaintained for 90.0 min
  3. concentrationFor work up methanol solution was concentrated atmospherically until the residual volume 6.0 rel
  4. temperatureThe resulting suspension was cooled to 20-25° C.
  5. stirringstirred for 1.0 hr
  6. filtrationThe product was filtered
  7. washwashed with ethyl acetate (200.0 ml, 4.0 rel. vol)
  8. customsucked dry for 30 min
  9. customThe product was dried under vacuum (100 mbar) at 50° C. for 8 hrs

Quellen und Nachweise

ORD-Eintrag
ord-61aa6bc533514ae8a2491bc850923a70
Quelldatensatz
uspto-grants-2011_05
Patentnummer
US07951833B2

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