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

반응식

HRID 220499 반응식
[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

참가 물질

6

반응물 5

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

생성물 1

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

실험 절차

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]+.

후처리

  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

출처 및 근거

ORD 기록
ord-2d5aa96a821c486eb0c630a139d4a83d
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08202873B2

연결된 노트

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