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

反応式

HRID 220499 の反応式
[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

参加物

6

反応物 5

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

生成物 1

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

実験手順

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]+.

後処理

  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

出典と根拠

ORDレコード
ord-2d5aa96a821c486eb0c630a139d4a83d
出典データセット
uspto-grants-2012_06
特許番号
US08202873B2

関連ノート

読み込み中…