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 220506노트

반응식

HRID 220506 반응식
[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

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

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]+.

후처리

  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

출처 및 근거

ORD 기록
ord-10a6424dd4844339a60df5552692da79
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08202873B2

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