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 220506Notes

Reaction equation

HRID 220506 reaction equation
[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

Participants

7

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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]+.

Workup

  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

Sources & evidence

ORD record
ord-10a6424dd4844339a60df5552692da79
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

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