1,2-Dichloroethane → 4-(1-Cyclopropyl-1h-pyrazol-4-ylmethyl)-3'-(4-fluoro-phenyl)-3,4,5,6-tetrahydro-2h-[1,2']bipyrazinyl hydrochloride

HRID 220516Notes

Reaction equation

HRID 220516 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.[CH:20]1([N:23]2[CH:27]=[C:26]([CH:28]=O)[CH:25]=[N:24]2)[CH2:22][CH2:21]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[Cl:44]CCCl>>[ClH:44].[CH:20]1([N:23]2[CH:27]=[C:26]([CH2:28][N:17]3[CH2:16][CH2:15][N:14]([C:9]4[C:8]([C:5]5[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=5)=[N:13][CH:12]=[CH:11][N:10]=4)[CH2:19][CH2:18]3)[CH:25]=[N:24]2)[CH2:22][CH2:21]1

Participants

5

Reactant 4

HCID 111,2-DichloroethaneHCID 5049666Sodium triacetoxyborohydrideHCID 574169141-Cyclopropyl-1H-pyrazole-4-carboxaldehydeHCID 673669592-(4-Fluorophenyl)-3-(piperazin-1-yl)pyrazine

Product 1

HCID 685946554-(1-Cyclopropyl-1h-pyrazol-4-ylmethyl)-3'-(4-fluoro-phenyl)-3,4,5,6-tetrahydro-2h-[1,2']bipyrazinyl hydrochlorideYield 7%

Procedure

Dissolve 3′-(4-Fluoro-phenyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (0.157 g, 0.608 mmol) in DCE (5 mL). Add 1-cyclopropyl-1H-pyrazole-4-carbaldehyde (0.354 g, 2.60 mmol) followed by sodium triacetoxyborohydride (0.193 g, 0.912 mmol) and stir at room temperature for 18 hr. Purify via SCX chromatography, followed by silica gel chromatography (eluting with 100:0 to 0:100 hexanes:ethyl acetate then 10:90 methanol:ethyl acetate), to give the free base of the title compound (16 mg, 7%). Dissolve this free base (0.014 g, 0.038 mmol) in methanol and add a solution of ammonium chloride (0.002 g, 0.038 mmol) in a minimal volume of methanol. Shake for 18 hr. at ambient temperature and concentrate to give the title compound (15 mg, 100%). MS (ES): m/z=379 [M+H]+.

Workup

  1. customPurify via SCX chromatography
  2. washeluting with 100:0 to 0:100 hexanes

Sources & evidence

ORD record
ord-d9fb4863e5d84422b3c314b4781febe2
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

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