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

HRID 220504Notes

Reaction equation

HRID 220504 reaction equation
[CH2:1]([N:3]1[C:7]([CH2:8][CH3:9])=[C:6]([CH2:10][CH:11]=O)[C:5]([CH2:13][CH3:14])=[N:4]1)[CH3:2].[F:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[C:23]([N:28]3[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]3)=[N:24][CH:25]=[CH:26][N:27]=2)=[CH:18][CH:17]=1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(Cl)[Cl:53]>>[ClH:53].[F:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[C:23]([N:28]3[CH2:29][CH2:30][N:31]([CH2:11][CH2:10][C:6]4[C:5]([CH2:13][CH3:14])=[N:4][N:3]([CH2:1][CH3:2])[C:7]=4[CH2:8][CH3:9])[CH2:32][CH2:33]3)=[N:24][CH:25]=[CH:26][N:27]=2)=[CH:18][CH:17]=1

Participants

6

Reactant 5

HCID 176Acetic AcidHCID 6344DichloromethaneHCID 5049666Sodium triacetoxyborohydrideHCID 673669592-(4-Fluorophenyl)-3-(piperazin-1-yl)pyrazineHCID 86641649(1,3,5-Triethyl-1H-pyrazol-4-yl)-acetaldehyde

Product 1

HCID 685947603'-(4-Fluorophenyl)-4-[2-(1,3,5-triethyl-1H-pyrazol-4-yl)-ethyl]-3,4,5,6-tetrahydro-2H-[1,2']bipyrazine hydrochlorideYield 83%

Procedure

Combine (1,3,5-triethyl-1H-pyrazol-4-yl)-acetaldehyde (0.16 g, 0.82 mmol) and 3′-(4-fluoro-phenyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (0.24 g, 0.91 mmol) in DCM (10 mL) and stir at room temperature for 15 min. Then add glacial acetic acid (0.07 mL, 1.23 mmol) and sodium triacetoxyborohydride (0.26 g, 1.23 mmol) and stir for 3 hr. at room temperature. Purify using SCX chromatography and further purify using silica gel chromatography (5% 7 M ammonia in methanol/DCM). Dissolve the free base in methanol (5 mL) and treat with ammonium chloride (0.037 g). Concentrate the resulting solution to give the title compound (0.032 g, 83%). MS: m/z=437.3[M+H]+.

Workup

  1. customat room temperature
  2. customPurify
  3. customfurther purify
  4. dissolutionDissolve the free base in methanol (5 mL)
  5. additiontreat with ammonium chloride (0.037 g)
  6. concentrationConcentrate the resulting solution

Sources & evidence

ORD record
ord-2e89aca8de5c43a093a6d2d04bea5ce2
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

Loading…