Acetic Acid → 3'-(4-Fluorophenyl)-4-[2-(3-isobutyl-5-methyl-1-pyridin-2-yl-1H-pyrazol-4-yl)-ethyl]-3,4,5,6-tetrahydro-2H-[1,2']bipyrazine hydrochloride

HRID 220505Notes

Reaction equation

HRID 220505 reaction equation
[CH2:1]([C:5]1[C:9]([CH2:10][CH:11]=O)=[C:8]([CH3:13])[N:7]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)[N:6]=1)[CH:2]([CH3:4])[CH3:3].[F:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[C:28]([N:33]3[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]3)=[N:29][CH:30]=[CH:31][N:32]=2)=[CH:23][CH:22]=1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(Cl)[Cl:58]>>[ClH:58].[F:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[C:28]([N:33]3[CH2:34][CH2:35][N:36]([CH2:11][CH2:10][C:9]4[C:5]([CH2:1][CH:2]([CH3:4])[CH3:3])=[N:6][N:7]([C:14]5[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=5)[C:8]=4[CH3:13])[CH2:37][CH2:38]3)=[N:29][CH:30]=[CH:31][N:32]=2)=[CH:23][CH:22]=1

Participants

6

Reactant 5

HCID 176Acetic AcidHCID 6344DichloromethaneHCID 5049666Sodium triacetoxyborohydrideHCID 673669592-(4-Fluorophenyl)-3-(piperazin-1-yl)pyrazineHCID 86641652(3-Isobutyl-5-methyl-1-pyridin-2-yl-1H-pyrazol-4-yl)-acetaldehyde

Product 1

HCID 685945743'-(4-Fluorophenyl)-4-[2-(3-isobutyl-5-methyl-1-pyridin-2-yl-1H-pyrazol-4-yl)-ethyl]-3,4,5,6-tetrahydro-2H-[1,2']bipyrazine hydrochlorideYield 50%

Procedure

Combine (3-isobutyl-5-methyl-1-pyridin-2-yl-1H-pyrazol-4-yl)-acetaldehyde (0.21 g, 0.82 mmol), 3′-(4-fluorophenyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (0.21 g, 0.82 mmol) in DCM (10 mL) and stir at room temperature for 15 min. Add glacial acetic acid (0.07 mL, 1.23 mmol) then sodium triacetoxyborohydride (0.26 g, 1.23 mmol). Stir at room temperature for 20 hr. Concentrate, then purify using SCX chromatography and further purify using silica gel chromatography, eluting with 5% 7 M ammonia in methanol:DCM. Dissolve the free base in methanol (5 mL) and treat with ammonium chloride (0.022 g). Concentrate the resulting solution to give the title compound as a white powder (0.22 g, 50%). MS: m/z=500.3 [M+H]+.

Workup

  1. concentrationConcentrate
  2. custompurify
  3. customfurther purify
  4. washeluting with 5% 7 M ammonia in methanol
  5. dissolutionDissolve the free base in methanol (5 mL)
  6. additiontreat with ammonium chloride (0.022 g)
  7. concentrationConcentrate the resulting solution

Sources & evidence

ORD record
ord-3118001bfa0546168184abf0e0c093a0
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

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