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

HRID 220518Notes

Reaction equation

HRID 220518 reaction equation
[N:1]1([C:7]2[C:12]([C:13]3[CH:18]=[CH:17][C:16]([C:19](=[O:21])[CH3:20])=[CH:15][CH:14]=3)=[N:11][CH:10]=[CH:9][N:8]=2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[CH3:22][C:23]1[C:27]([CH:28]=O)=[CH:26][N:25]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[N:24]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[Cl:50]CCCl>>[ClH:50].[CH3:22][C:23]1[C:27]([CH2:28][N:4]2[CH2:5][CH2:6][N:1]([C:7]3[C:12]([C:13]4[CH:14]=[CH:15][C:16]([C:19](=[O:21])[CH3:20])=[CH:17][CH:18]=4)=[N:11][CH:10]=[CH:9][N:8]=3)[CH2:2][CH2:3]2)=[CH:26][N:25]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[N:24]=1

Participants

5

Reactant 4

HCID 111,2-DichloroethaneHCID 8488843-methyl-1-phenyl-1H-pyrazole-4-carbaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 685951741-[4-(3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-3'-yl)-phenyl]-ethanone

Product 1

HCID 685974181-{4-[4-(3-Methyl-1-phenyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-3'-yl]-phenyl}-ethanone hydrochlorideYield 18%

Procedure

Dissolve 1-[4-(3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl-3′-yl)-phenyl]-ethanone (0.5 g, 1.77 mmol) in 1,2 dichloroethane (4 mL). Add 3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde (1.5 eq., 0.495 g, 2.66 mmol). Stir for 30 min. Add sodium triacetoxyborohydride (2.0 eq., 0.75 g, 3.54 mmol). Stir at room temperature for 48 hr. Purify by SCX column followed by normal phase chromatography with a gradient of 100% EtOAc-5% 7N NH3 in methanol/EtOAc to give the freebase of the title compound (0.15 g, 18% yield). MS (ES): m/z=453.2 [M+H]+. Dissolve (0.15 g, 0.33 mmol) in a mixture of acetonitrile (2 mL) and water (3 mL). Add aq. 1N HCl (1 eq., 0.33 mmol, 0.33 mL). Freeze the solution to −78° C. in a dry-ice/acetone bath. Place the solution in the lyophilizer for 48 hr. to give the title compound (0.156 g, 97% yield). MS (ES): m/z=453.2[M+H]+.

Workup

  1. stirringStir at room temperature for 48 hr
  2. customPurify by SCX column

Sources & evidence

ORD record
ord-b76a6805d62044ef8c73ff57ab967bdb
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

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