Sodium hydride → 1-[3-(Dimethylamino)propyl]-3-(1-methyl-4-piperidinyl)-1H-indazole difumarate

HRID 652133

Reaktionsgleichung

Reaktionsgleichung von HRID 652133
[H-].[Na+].[CH3:3][N:4]1[CH2:9][CH2:8][CH:7]([C:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[NH:12][N:11]=2)[CH2:6][CH2:5]1.[CH3:19][N:20]([CH2:22][CH2:23][CH2:24]Cl)[CH3:21].[C:26]([OH:33])(=[O:32])/[CH:27]=[CH:28]/[C:29]([OH:31])=[O:30]>CN(C)C=O.C1(C)C=CC=CC=1.C(#N)C.O>[C:26]([OH:33])(=[O:32])/[CH:27]=[CH:28]/[C:29]([OH:31])=[O:30].[C:26]([OH:33])(=[O:32])/[CH:27]=[CH:28]/[C:29]([OH:31])=[O:30].[CH3:19][N:20]([CH3:21])[CH2:22][CH2:23][CH2:24][N:12]1[C:13]2[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:10]([CH:7]2[CH2:6][CH2:5][N:4]([CH3:3])[CH2:9][CH2:8]2)=[N:11]1

Komponenten

9

Edukt 4

HCID 24758Sodium hydrideHCID 669603-Chloro-N,N-dimethyl-1-propanamineHCID 444972Fumaric AcidHCID 178480237HCID 178480237, Verbindung

Produkt 1

HCID 140325031-[3-(Dimethylamino)propyl]-3-(1-methyl-4-piperidinyl)-1H-indazole difumarateAusbeute 18,7 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 962WaterLösungsmittelHCID 1140TolueneLösungsmittelHCID 6228DimethylformamideLösungsmittel2×HCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

To a stirred suspension of 1.15 g of sodium hydride (50% oil dispersion) in 30 ml of dimethylformamide, under nitrogen, was added dropwise 4.3 g of 3-(1-methyl-4-piperidinyl)-1H-indazole dissolved in 30 ml of hot dimethylformamide. After stirring at ambient temperature for 1 hr, a solution of 3.3 g of dimethylaminopropylchloride in 30 ml of toluene was added dropwise. The reaction was then heated at 60° for 1 hr and then stirred at ambient temperature for 16 hrs. The reaction mixture was poured into water and the aqueous suspension was extracted with ethyl acetate (3×150 ml). The organic extracts were combined, washed with water, brine, dried over anhydrous magnesium sulfate, and the solvent evaporated in vacuo to yield an oil. The oil was dissolved in 25 ml of acetonitrile and 4.6 g of fumaric acid was added. The mixture was warmed on the steam bath (ca. 15 min), and then left at ambient temperature for 15 hrs. The resultant solid was filtered and recrystallized from dimethylformamide (thrice) with cooling (ca. 5°) to yield 1.4 g (18.7%) of product, mp 161°-163° C.

Aufarbeitung

  1. temperatureThe reaction was then heated at 60° for 1 hr
  2. stirringstirred at ambient temperature for 16 hrs
  3. extractionthe aqueous suspension was extracted with ethyl acetate (3×150 ml)
  4. washwashed with water, brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customthe solvent evaporated in vacuo
  7. customto yield an oil
  8. temperatureThe mixture was warmed on the steam bath (ca. 15 min)
  9. waitleft at ambient temperature for 15 hrs
  10. filtrationThe resultant solid was filtered
  11. customrecrystallized from dimethylformamide (thrice)
  12. temperaturewith cooling (ca. 5°)

Quellen und Nachweise

ORD-Eintrag
ord-721d2550891b4641a74cbbba3e6bdff2
Quelldatensatz
uspto-grants-1987_06
Patentnummer
US04670447

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