Hydrochloric Acid → N-{4-[4-(3,5-Dimethyl-1-pyridin-2-yl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-3'-yl]-benzyl}-acetamide hydrochloride

HRID 220603Notes

Reaction equation

HRID 220603 reaction equation
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[N:15]1([C:21]2[C:26]([C:27]3[CH:37]=[CH:36][C:30]([CH2:31][NH:32][C:33](=[O:35])[CH3:34])=[CH:29][CH:28]=3)=[N:25][CH:24]=[CH:23][N:22]=2)[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1.[CH3:38][C:39]1[C:43]([CH:44]=O)=[C:42]([CH3:46])[N:41]([C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][N:48]=2)[N:40]=1.[ClH:53]>C1COCC1>[ClH:53].[CH3:38][C:39]1[C:43]([CH2:44][N:18]2[CH2:19][CH2:20][N:15]([C:21]3[C:26]([C:27]4[CH:28]=[CH:29][C:30]([CH2:31][NH:32][C:33](=[O:35])[CH3:34])=[CH:36][CH:37]=4)=[N:25][CH:24]=[CH:23][N:22]=3)[CH2:16][CH2:17]2)=[C:42]([CH3:46])[N:41]([C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][N:48]=2)[N:40]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 5049666Sodium triacetoxyborohydrideHCID 220544033,5-dimethyl-1-(pyridin-2-yl)-1H-pyrazole-4-carbaldehydeHCID 68595017N-[4-(3,4,5,6-Tetrahydro-2H-[1,2']bipyrazinyl-3'-yl)-benzyl]-acetamide

Product 1

HCID 68595870N-{4-[4-(3,5-Dimethyl-1-pyridin-2-yl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-3'-yl]-benzyl}-acetamide hydrochlorideYield 54%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Add sodium triacetoxyborohydride (231 mg, 1.04 mmol) to a solution of N-[4-(3,4,5,6-Tetrahydro-2H-[1,2′]bipyrazinyl-3′-yl)-benzyl]-acetamide (215 mg, 0.69 mmol) and 3,5-dimethyl-1-pyridin-2-yl-1H-pyrazole-4-carboxaldehyde (208 mg, 1.03 mmol) in THF (3.5 mL). Maintain stirring for 3 hr. and quench by adding NaHCO3 (5 mL). Extract with DCM (3×10 mL) and discard the aq. phase filtering through an IST phase separator Frit®. Concentrate to dryness and purify by preparative HPLC then purify by SCX-2® ion exchange chromatography, eluting with 2 M NH3 in MeOH to give the free base. Prepare the hydrochloride salt by adding HCl and lyophilise the solution to give the title compound (200 mg, 54%). MS (ES): m/z=497 [M+H]+.

Workup

  1. temperatureMaintain
  2. customand quench
  3. additionby adding NaHCO3 (5 mL)
  4. extractionExtract with DCM (3×10 mL)
  5. filtrationfiltering through an IST phase separator Frit®
  6. concentrationConcentrate to dryness
  7. custompurify by preparative HPLC
  8. customthen purify by SCX-2® ion exchange chromatography
  9. washeluting with 2 M NH3 in MeOH
  10. customto give the free base

Sources & evidence

ORD record
ord-2068e9f531844343826f68e2e7b38aae
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

Loading…