1,2-Dichloroethane → 3'-(4-Fluoro-phenyl)-4-(1-phenyl-1h-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2h-[1,2']bipyrazine hydrochloride salt

HRID 220499

Reaktionsgleichung

Reaktionsgleichung von HRID 220499
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([N:14]3[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]3)=[N:10][CH:11]=[CH:12][N:13]=2)=[CH:4][CH:3]=1.[C:20]1([N:26]2[CH:30]=[C:29]([CH:31]=O)[CH:28]=[N:27]2)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C.[Cl:51]CCCl>>[ClH:51].[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([N:14]3[CH2:15][CH2:16][N:17]([CH2:31][C:29]4[CH:28]=[N:27][N:26]([C:20]5[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=5)[CH:30]=4)[CH2:18][CH2:19]3)=[N:10][CH:11]=[CH:12][N:13]=2)=[CH:4][CH:3]=1

Komponenten

6

Edukt 5

HCID 111,2-DichloroethaneHCID 176Acetic AcidHCID 9520891-Phenyl-1H-pyrazole-4-carbaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 673669592-(4-Fluorophenyl)-3-(piperazin-1-yl)pyrazine

Produkt 1

HCID 685966613'-(4-Fluoro-phenyl)-4-(1-phenyl-1h-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2h-[1,2']bipyrazine hydrochloride saltAusbeute 100 %

Versuchsvorschrift

Form the free base of 3′-(4-fluoro-phenyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl dihydrochloride by SCX-2® chromatography washing with methanol then eluting with 2M ammonia in methanol. Dissolve 3′-(4-fluoro-phenyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (0.200 g, 0.774 mmol) in DCE (5 mL). Add 1-phenyl-1H-pyrazole-4-carbaldehyde (0.200 g, 1.16 mmol, 1.5 eq.). Stir at room temperature for 20-30 min. Add sodium triacetoxyborohydride (0.33 g, 1.55 mmol, 2 eq.) followed by acetic acid (0.048 g, 0.81 mmol, 1.05 eq.). Stir the reaction mixture at room temperature for 48 hr. Purify by SCX cartridge, followed by reverse phase chromatography to obtain the freebase of the title compound (0.360 g, 0.87 mmol, 100% yield). MS (ES): m/z=415.3[M+H]. Dissolve in methanol (5 mL). Add ammonium chloride (0.047 g, 0.87 mmol, 1 eq.). Stir the reaction mixture at room temperature for 2 hr. and concentrate to give the title compound (0.327 g, 83% yield for salt formation). MS (ES): m/z=415.3[M+H]+.

Aufarbeitung

  1. washForm the free base of 3′-(4-fluoro-phenyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl dihydrochloride by SCX-2® chromatography washing with methanol
  2. washthen eluting with 2M ammonia in methanol
  3. stirringStir the reaction mixture at room temperature for 48 hr
  4. customPurify by SCX cartridge

Quellen und Nachweise

ORD-Eintrag
ord-2d5aa96a821c486eb0c630a139d4a83d
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08202873B2

Verknüpfte Notizen

Wird geladen…