1,2-Dichloroethane → 2-{4-[3'-(2-Fluoro-phenyl)-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-ylmethyl]-pyrazol-1-yl}-ethanol hydrochloride

HRID 220510Notes

Reaction equation

HRID 220510 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:9]([N:14]2[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)=[N:10][CH:11]=[CH:12][N:13]=1.[OH:20][CH2:21][CH2:22][N:23]1[CH:27]=[C:26]([CH:28]=O)[CH:25]=[N:24]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[Cl:44]CCCl>>[ClH:44].[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:9]([N:14]2[CH2:15][CH2:16][N:17]([CH2:28][C:26]3[CH:25]=[N:24][N:23]([CH2:22][CH2:21][OH:20])[CH:27]=3)[CH2:18][CH2:19]2)=[N:10][CH:11]=[CH:12][N:13]=1

Participants

5

Reactant 4

HCID 111,2-DichloroethaneHCID 5049666Sodium triacetoxyborohydrideHCID 247026081-(2-hydroxyethyl)-1H-pyrazole-4-carbaldehyde2×HCID 673675203'-(2-Fluoro-phenyl)-3,4,5,6-tetrahydro-2h-[1,2']bipyrazinyl

Product 1

HCID 685942492-{4-[3'-(2-Fluoro-phenyl)-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-ylmethyl]-pyrazol-1-yl}-ethanol hydrochlorideYield 37%

Procedure

Dissolve 3′-(2-fluoro-phenyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (0.213 g, 0.825 mmol) in DCE (5 mL). Add 1-(2-hydroxy-ethyl)-1H-pyrazole-4-carbaldehyde (0.137 g, 0.990 mmol) followed by sodium triacetoxyborohydride (0.262 g, 1.24 mmol) and stir at ambient temperature for 18 hr. Add additional 1-(2-hydroxy-ethyl)-1H-pyrazole-4-carbaldehyde (0.093 g, 0.663 mmol) and stir at ambient 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 (116 mg, 37%). Dissolve the free base (0.114 g, 0.298 mmol) in methanol and add a solution of ammonium chloride (0.016 g, 0.298 mmol) in a minimal volume of methanol. Shake for 18 hr. at ambient temperature and concentrate to give the title compound (125 mg, 100%). MS (ES): m/z=383[M+H]+.

Workup

  1. stirringstir at ambient temperature for 18 hr
  2. customPurify via SCX chromatography
  3. wash(eluting with 100:0 to 0:100 hexanes

Sources & evidence

ORD record
ord-2573102a1a6441df97adadc0dfd7b9b3
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

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