1,2-Dichloroethane → 4-(3,5-Dimethyl-1-phenyl-1h-pyrazol-4-ylmethyl)-3'-(4-fluorophenyl)-3,4,5,6-tetrahydro-2h-[1,2']bipyrazine hydrochloride

HRID 220498Notes

Reaction equation

HRID 220498 reaction equation
[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.[CH3:20][C:21]1[C:25]([CH:26]=O)=[C:24]([CH3:28])[N:23]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[N:22]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C.[Cl:53]CCCl>>[ClH:53].[CH3:20][C:21]1[C:25]([CH2:26][N:17]2[CH2:16][CH2:15][N:14]([C:9]3[C:8]([C:5]4[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=4)=[N:13][CH:12]=[CH:11][N:10]=3)[CH2:19][CH2:18]2)=[C:24]([CH3:28])[N:23]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[N:22]=1

Participants

6

Reactant 5

HCID 111,2-DichloroethaneHCID 176Acetic AcidHCID 891791H-Pyrazole-4-carboxaldehyde, 3,5-dimethyl-1-phenyl-HCID 5049666Sodium triacetoxyborohydrideHCID 673669592-(4-Fluorophenyl)-3-(piperazin-1-yl)pyrazine

Product 1

HCID 685948304-(3,5-Dimethyl-1-phenyl-1h-pyrazol-4-ylmethyl)-3'-(4-fluorophenyl)-3,4,5,6-tetrahydro-2h-[1,2']bipyrazine hydrochlorideYield 65%

Procedure

Dissolve 3′-(4-fluorophenyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (0.200 g, 0.774 mmol) in DCE (10 mL). Add 3,5-dimethyl-1-phenylpyrazole-4-carboxaldehyde (0.186 g, 0.929 mmol), and stir at room temperature for 10 min. Add sodium triacetoxyborohydride (0.247 g, 1.16 mmol) followed by acetic acid (47 μL, 0.813 mmol). Stir at room temperature for 18 hr. Purify via SCX chromatography, followed by silica gel chromatography, eluting with 0:100 to 10:90 methanol:DCM, followed by reverse phase chromatography to give the free base of the title compound (221 mg, 65%). Dissolve the free base (0.099 g, 0.225 mmol) in methanol and add a solution of ammonium chloride (0.012 g, 0.225 mmol) in a minimal volume of methanol. Shake for 1 hr. at room temperature and concentrate to give the title compound (108 mg, 100%). MS (ES): m/z=443 [M+H]+.

Workup

  1. customPurify via SCX chromatography
  2. washeluting with 0:100 to 10:90 methanol

Sources & evidence

ORD record
ord-37418054f4144a2e946e2439bb2acac6
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

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