Acetic Acid → 3'-(4-Fluorophenyl)-4-[2-(3-isobutyl-5-methyl-1-pyridin-2-yl-1H-pyrazol-4-yl)-ethyl]-3,4,5,6-tetrahydro-2H-[1,2']bipyrazine hydrochloride

HRID 220505ノート

反応式

HRID 220505 の反応式
[CH2:1]([C:5]1[C:9]([CH2:10][CH:11]=O)=[C:8]([CH3:13])[N:7]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)[N:6]=1)[CH:2]([CH3:4])[CH3:3].[F:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[C:28]([N:33]3[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]3)=[N:29][CH:30]=[CH:31][N:32]=2)=[CH:23][CH:22]=1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(Cl)[Cl:58]>>[ClH:58].[F:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[C:28]([N:33]3[CH2:34][CH2:35][N:36]([CH2:11][CH2:10][C:9]4[C:5]([CH2:1][CH:2]([CH3:4])[CH3:3])=[N:6][N:7]([C:14]5[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=5)[C:8]=4[CH3:13])[CH2:37][CH2:38]3)=[N:29][CH:30]=[CH:31][N:32]=2)=[CH:23][CH:22]=1

参加物

6

反応物 5

HCID 176Acetic AcidHCID 6344DichloromethaneHCID 5049666Sodium triacetoxyborohydrideHCID 673669592-(4-Fluorophenyl)-3-(piperazin-1-yl)pyrazineHCID 86641652(3-Isobutyl-5-methyl-1-pyridin-2-yl-1H-pyrazol-4-yl)-acetaldehyde

生成物 1

HCID 685945743'-(4-Fluorophenyl)-4-[2-(3-isobutyl-5-methyl-1-pyridin-2-yl-1H-pyrazol-4-yl)-ethyl]-3,4,5,6-tetrahydro-2H-[1,2']bipyrazine hydrochloride収率 50%

実験手順

Combine (3-isobutyl-5-methyl-1-pyridin-2-yl-1H-pyrazol-4-yl)-acetaldehyde (0.21 g, 0.82 mmol), 3′-(4-fluorophenyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (0.21 g, 0.82 mmol) in DCM (10 mL) and stir at room temperature for 15 min. Add glacial acetic acid (0.07 mL, 1.23 mmol) then sodium triacetoxyborohydride (0.26 g, 1.23 mmol). Stir at room temperature for 20 hr. Concentrate, then purify using SCX chromatography and further purify using silica gel chromatography, eluting with 5% 7 M ammonia in methanol:DCM. Dissolve the free base in methanol (5 mL) and treat with ammonium chloride (0.022 g). Concentrate the resulting solution to give the title compound as a white powder (0.22 g, 50%). MS: m/z=500.3 [M+H]+.

後処理

  1. concentrationConcentrate
  2. custompurify
  3. customfurther purify
  4. washeluting with 5% 7 M ammonia in methanol
  5. dissolutionDissolve the free base in methanol (5 mL)
  6. additiontreat with ammonium chloride (0.022 g)
  7. concentrationConcentrate the resulting solution

出典と根拠

ORDレコード
ord-3118001bfa0546168184abf0e0c093a0
出典データセット
uspto-grants-2012_06
特許番号
US08202873B2

反応ノート

読み込み中…