1,2-Dichloroethane → 3'-(4-Fluorophenyl)-4-[3-(1,3,5-trimethyl-1h-pyrazol-4-yl)-propyl]-3,4,5,6-tetrahydro-2h-[1,2']bipyrazine hydrochloride

HRID 220502Notes

Reaction equation

HRID 220502 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][N:21]1[C:25]([CH3:26])=[C:24]([CH2:27][CH2:28][CH:29]=O)[C:23]([CH3:31])=[N:22]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[Cl:46]CCCl>>[ClH:46].[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([N:14]3[CH2:15][CH2:16][N:17]([CH2:29][CH2:28][CH2:27][C:24]4[C:23]([CH3:31])=[N:22][N:21]([CH3:20])[C:25]=4[CH3:26])[CH2:18][CH2:19]3)=[N:10][CH:11]=[CH:12][N:13]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 4

HCID 111,2-DichloroethaneHCID 5049666Sodium triacetoxyborohydrideHCID 673669592-(4-Fluorophenyl)-3-(piperazin-1-yl)pyrazineHCID 866416503-(1,3,5-Trimethyl-1H-pyrazol-4-yl)-propionaldehyde

Product 1

HCID 685957213'-(4-Fluorophenyl)-4-[3-(1,3,5-trimethyl-1h-pyrazol-4-yl)-propyl]-3,4,5,6-tetrahydro-2h-[1,2']bipyrazine hydrochlorideYield 78%

Procedure

Dissolve 3′-(4-fluorophenyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (0.300 g, 1.16 mmol) in DCE (15 mL). Add 3-(1,3,5-trimethyl-1H-pyrazol-4-yl)-propionaldehyde (0.232 g, 1.39 mmol), and stir at room temperature for 10 min. Add sodium triacetoxyborohydride (0.369 g, 1.74 mmol) and stir at room temperature for 18 hr. Purify by SCX chromatography, followed by silica gel chromatography, eluting with 45:45:10 DCM:hexanes:ethanol, to give the free base of the title compound (368 mg, 78%). Dissolve the free base (0.362 g, 0.888 mmol) in methanol and add a solution of ammonium chloride (0.047 g, 0.888 mmol) in a minimal volume of methanol. Shake for 3 hr. at room temperature and concentrate to give the title compound (395 mg, 100%). MS (ES): m/z=409 [M+H]+.

Workup

  1. customPurify by SCX chromatography
  2. washeluting with 45:45:10 DCM

Sources & evidence

ORD record
ord-394a4063c8ab4e4ebde7eb93766a17d1
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

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