Acetic Acid → 3'-(4-Fluorophenyl)-4-(1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazine dihydrochloride

HRID 220506ノート

反応式

HRID 220506 の反応式
[CH3:1][N:2]1[CH:6]=[C:5]([CH:7]=O)[C:4]([C:9]([F:12])([F:11])[F:10])=[N:3]1.[ClH:13].Cl.[F:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[C:23]([N:28]3[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]3)=[N:24][CH:25]=[CH:26][N:27]=2)=[CH:18][CH:17]=1.C(N(CC)CC)C.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[ClH:13].[ClH:13].[F:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[C:23]([N:28]3[CH2:29][CH2:30][N:31]([CH2:7][C:5]4[C:4]([C:9]([F:12])([F:11])[F:10])=[N:3][N:2]([CH3:1])[CH:6]=4)[CH2:32][CH2:33]3)=[N:24][CH:25]=[CH:26][N:27]=2)=[CH:18][CH:17]=1

参加物

7

反応物 5

HCID 176Acetic AcidHCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 533020711-methyl-3-(trifluoromethyl)-1H-pyrazole-4-carbaldehydeHCID 673669583'-(4-fluoro-phenyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl dihydrochloride

生成物 1

HCID 866416603'-(4-Fluorophenyl)-4-(1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazine dihydrochloride収率 149.2%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

Combine 1-methyl-3-trifluoromethyl-1H-pyrazole-4-carbaldehyde (0.17 g, 0.97 mmol) and 3′-(4-fluorophenyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl dihydrochloride (0.35 g, 1.06 mmol) in DCM (20 mL) and treat with triethylamine (0.30 mL, 2.12 mmol). After stirring for 15 min, add glacial acetic acid (0.08 mL, 1.46 mmol) then sodium triacetoxyborohydride (0.31 g, 1.46 mmol). Stir at room temperature for 18 hr. Concentrate and purify using SCX chromatography and further purify using silica gel chromatography (5% 7 M ammonia in methanol/DCM). Dissolve the free base in methanol (5 mL) and treat with ammonium chloride (0.107 g). Concentrate the resulting solution to give the title compound (0.39 g, 81%). MS: m/z=421.3 [M+H]+.

後処理

  1. stirringStir at room temperature for 18 hr
  2. concentrationConcentrate
  3. custompurify
  4. customfurther purify
  5. dissolutionDissolve the free base in methanol (5 mL)
  6. additiontreat with ammonium chloride (0.107 g)
  7. concentrationConcentrate the resulting solution

出典と根拠

ORDレコード
ord-10a6424dd4844339a60df5552692da79
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…