Acetic Acid → 1-[4-(5-Bromo-[1,2,4]triazolo[1,5-a]pyrazin-8-ylamino)-phenyl]-4-isopropyl-piperazin-2-one

HRID 605980Notes

Reaction equation

HRID 605980 reaction equation
[Br:1][C:2]1[N:7]2[N:8]=[CH:9][N:10]=[C:6]2[C:5]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([N:18]3[CH2:23][CH2:22][NH:21][CH2:20][C:19]3=[O:24])=[CH:14][CH:13]=2)=[N:4][CH:3]=1.C(O)(=O)C.CC([O-])=O.[Na+].[CH3:34][C:35]([CH3:37])=O.[BH3-]C#N.[Na+].Cl>CO>[Br:1][C:2]1[N:7]2[N:8]=[CH:9][N:10]=[C:6]2[C:5]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([N:18]3[CH2:23][CH2:22][N:21]([CH:35]([CH3:37])[CH3:34])[CH2:20][C:19]3=[O:24])=[CH:14][CH:13]=2)=[N:4][CH:3]=1

Participants

8

Reactant 6

HCID 176Acetic AcidHCID 180AcetoneHCID 313Hydrochloric AcidHCID 517045Sodium AcetateHCID 5003444Sodium cyanoborohydrideHCID 57590076HCID 57590076, compound

Product 1

HCID 575900031-[4-(5-Bromo-[1,2,4]triazolo[1,5-a]pyrazin-8-ylamino)-phenyl]-4-isopropyl-piperazin-2-oneYield 25%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 1-[4-(5-bromo-[1,2,4]triazolo[1,5-a]pyrazin-8-ylamino)-phenyl]-piperazin-2-one (example 31, step 2) (180 mg, 0.47 mmol) in MeOH (4 mL) are added acetic acid (0.03 mL, 0.47 mmol), NaOAc (38 mg, 0.47 mmol) and acetone (0.2 mL, 1.18 mmol). The reaction mixture is stirred at room temperature for 1 hour then NaCNBH3 (60 mg, 0.94 mmol) is added and the mixture is stirred at 40° C. overnight. After cooling to room temperature, the reaction mixture is acidified with conc. HCl (pH 1) and concentrated in vacuo. The residue is partitioned between 6N NaOH and DCM. The aqueous layer is extracted with DCM (3×) and the combined organic layers are dried over MgSO4 and concentrated in vacuo to afford a crude compound which is purified by silica gel column chromatography. Elution with DCM and 98:2 DCM:MeOH affords the title compound as a yellow solid (45 mg, 25%).

Workup

  1. stirringthe mixture is stirred at 40° C. overnight
  2. temperatureAfter cooling to room temperature
  3. concentrationconcentrated in vacuo
  4. customThe residue is partitioned between 6N NaOH and DCM
  5. extractionThe aqueous layer is extracted with DCM (3×)
  6. dry with materialthe combined organic layers are dried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customto afford a crude compound which
  9. customis purified by silica gel column chromatography
  10. washElution with DCM and 98:2 DCM

Sources & evidence

ORD record
ord-5a3d4d07bae24feb82a6a3632e3aba39
Source dataset
uspto-grants-2011_03
Patent number
US07915256B2

Reaction notes

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