Hydrochloric Acid → 2-[3-(3-[(Dimethylamino)methyl]phenethylamino)6-methyl-2-oxo-1(2H)-pyrazinyl]acetic Acid

HRID 2228734Notes

Reaction equation

HRID 2228734 reaction equation
C([O:8][C:9](=[O:33])[CH2:10][N:11]1[C:16](=[O:17])[C:15]([NH:18][CH2:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([CH2:27][N:28]([CH3:30])[CH3:29])[CH:22]=2)=[N:14][C:13](Cl)=[C:12]1[CH3:32])C1C=CC=CC=1.N1C2C(=CC(CN)=CC=2)C=C1.C1C=CC2N(O)N=NC=2C=1.Cl.CN1CCOCC1>CO.O.[OH-].[OH-].[Pd+2].CN(C=O)C>[CH3:29][N:28]([CH2:27][C:23]1[CH:22]=[C:21]([CH:26]=[CH:25][CH:24]=1)[CH2:20][CH2:19][NH:18][C:15]1[C:16](=[O:17])[N:11]([CH2:10][C:9]([OH:33])=[O:8])[C:12]([CH3:32])=[CH:13][N:14]=1)[CH3:30]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 54791(1H-indol-5-yl)methanamineHCID 757711-HydroxybenzotriazoleHCID 18470815Benzyl 2-[3-chloro-5-(3-[(dimethylamino)methyl]phenethylamino)-2-methyl-6-oxo-1(6H)-pyrazinyl]acetate

Product 1

HCID 184708222-[3-(3-[(Dimethylamino)methyl]phenethylamino)6-methyl-2-oxo-1(2H)-pyrazinyl]acetic AcidYield 10%

Reagents, catalysts & solvents 3

HCID 9942167Palladium hydroxideCatalystHCID 6228DimethylformamideSolventHCID 22242641Methanol--water (1/1)Solvent

Procedure

Benzyl-2-[3-chloro-5-(3-[(dimethylamino)methyl]phenethylamino)-2-methyl-6-oxo-1(6H)-pyrazinyl]acetate (preparation 20) (137 mg, 0.29 mmol) was dissolved in methanol:water (10:2, 20 ml), treated with Pearlman's catalyst (10 mg) and stirred under a hydrogen atmosphere (60 psi, room temperature, 2.5 hr). The catalyst was removed by filtration, followed by evaporation of the solvent and azeotroping with CH2Cl2 to yield a crude yellow solid. To the crude mixture, 1H-indol-5-ylmethylamine (preparation 8) (43 mg, 0.29 mmol), HOBT (46 mg, 0.34 mmol), WSCDI.HCl (74 mg, 0.39 mmol), N-methylmorpholine (0.061 ml, 0.55 mmol) and DMF (5 ml) were stirred at room temperature for 18 hr. The resultant mixture was evaporated to dryness and azeotroped with CH2Cl2. Water (2 ml) was added followed by aq Na2CO3 (a few drops) and the residue treated with ethyl acetate and methanol. The organic layer was separated, dried over MgSO4. Filtration away from the drying agent followed by evaporation of the solvent gave the crude product which was purified by chromatography (SiO2, gradient elution with 100% CH2Cl2; 95:5 CH2Cl2:MeOH; 95:5:0.5 CH2Cl2:MeOH:NH3) to give the desired product (10 mg, 7%).

Workup

  1. customThe catalyst was removed by filtration
  2. customfollowed by evaporation of the solvent
  3. customazeotroping with CH2Cl2
  4. customto yield a crude yellow solid
  5. customThe resultant mixture was evaporated to dryness
  6. customazeotroped with CH2Cl2
  7. additionWater (2 ml) was added
  8. additionthe residue treated with ethyl acetate and methanol
  9. customThe organic layer was separated
  10. dry with materialdried over MgSO4
  11. filtrationFiltration away from the drying agent
  12. customfollowed by evaporation of the solvent
  13. customgave the crude product which
  14. customwas purified by chromatography (SiO2, gradient elution with 100% CH2Cl2; 95:5 CH2Cl2:MeOH; 95:5:0.5 CH2Cl2:MeOH:NH3)

Sources & evidence

ORD record
ord-dbf289b8ea7244309bb2c8edfc16ac52
Source dataset
uspto-grants-2002_07
Patent number
US06417203B1

Reaction notes

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