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

HRID 220517Notes

Reaction equation

HRID 220517 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[N:27]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[N:26]=[CH:25][C:24]=1[CH:34]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[Cl:50]CCCl>>[ClH:50].[CH3:22][C:23]1[N:27]([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[N:26]=[CH:25][C:24]=1[CH2:34][N:4]1[CH2:5][CH2:6][N:1]([C:7]2[C:12]([C:13]3[CH:14]=[CH:15][C:16]([C:19](=[O:21])[CH3:20])=[CH:17][CH:18]=3)=[N:11][CH:10]=[CH:9][N:8]=2)[CH2:2][CH2:3]1

Participants

5

Reactant 4

HCID 111,2-DichloroethaneHCID 27764375-Methyl-1-phenyl-1H-pyrazole-4-carboxaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 685951741-[4-(3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-3'-yl)-phenyl]-ethanone

Product 1

HCID 685952071-{4-[4-(5-Methyl-1-phenyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-3'-yl]-phenyl}-ethanone hydrochlorideYield 78%

Procedure

Dissolve 1-[4-(3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl-3′-yl)-phenyl]-ethanone (0.250 g, 0.885 mmol) in 1,2 dichloroethane (4 mL). Add 5-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde (1.5 eq., 0.250 g, 1.33 mmol). Stir for 30 min. Add sodium triacetoxyborohydride (2.0 eq., 0.375 g, 1.77 mmol). Stir at room temperature for 48 hr. Purify by SCX column followed by normal phase chromatography with a gradient of 100% EtOAc to 5% 7N ammonia in methanol/EtOAc to give the freebase of the title compound, (0.312 g, 78% yield). MS (ES): m/z=453.2[M+H]. Dissolve in a mixture of acetonitrile (2 mL) and water (3 mL). Add aq. 1N HCl (1 eq., 0.69 mmol, 0.69 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 (0.268 g, 80% 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-ca87527e461048acb70ed2058a6972ee
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

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