Triethylamine → Benzyl 2-[3-[(3-[(tert-Butoxycarbonyl)(methyl)amino]methylphenethyl)amino]-5-chloro-6-methyl-2-oxo-1(2H)-pyrazinyl]acetate

HRID 2228731Notes

Reaction equation

HRID 2228731 reaction equation
[C:1]([O:5][C:6](=[O:19])[N:7]([CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([CH2:16][CH2:17][NH2:18])[CH:11]=1)[CH3:8])([CH3:4])([CH3:3])[CH3:2].[CH2:20]([O:27][C:28](=[O:40])[CH2:29][N:30]1[C:35](=[O:36])[C:34](Cl)=[N:33][C:32]([Cl:38])=[C:31]1[CH3:39])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C(N(CC)CC)C>C(OCC)(=O)C>[C:1]([O:5][C:6]([N:7]([CH2:9][C:10]1[CH:11]=[C:12]([CH:13]=[CH:14][CH:15]=1)[CH2:16][CH2:17][NH:18][C:34]1[C:35](=[O:36])[N:30]([CH2:29][C:28]([O:27][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:40])[C:31]([CH3:39])=[C:32]([Cl:38])[N:33]=1)[CH3:8])=[O:19])([CH3:3])([CH3:2])[CH3:4]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 10663926Benzyl 2-[3,5-dichloro-2-methyl-6-oxo-1(6H)-pyrazinyl]acetateHCID 18470795tert-Butyl N-[3-(2-aminoethyl)benzyl]-N-methylcarbamate

Product 1

HCID 18470853Benzyl 2-[3-[(3-[(tert-Butoxycarbonyl)(methyl)amino]methylphenethyl)amino]-5-chloro-6-methyl-2-oxo-1(2H)-pyrazinyl]acetateYield 75%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

tert-Butyl-N-[3-(2-aminoethyl)benzyl]-N-methylcarbamate (preparation 15) (0.5 g, 1.89 mmol), benzyl-2-[3,5-dichloro-2-methyl-6-oxo-1(6H)-pyrazinyl]acetate (preparation 17) (0.6 g, 1.83 mmol) and triethylamine (0.5 ml, 3.66 mmol) in ethyl acetate (30 ml) were stirred at reflux for 24 hr. The resultant mixture was diluted with ethyl acetate (20 ml) and washed with water, sat aq brine, dried over MgSO4. Removal of the drying agent by filtration followed by evaporation of the solvent gave a red oil which was purified by chromatography (SiO2, gradient elution with 100% CH2Cl2; 99:1 CH2Cl2:MeOH; 98:2 CH2Cl2:MeOH) to give the desired product (0.76 g, 75%). 1H NMR (CDCl3) δ 1.45 (s, 9H), 2.20 (s, 3H), 2.80 (s, br, 3H), 2.90 (t, 2H), 3.70 (m, 2H), 4.20 (s, br, 2H), 4.80 (s, 2H), 5.20 (s, 2H), 6.10 (m, br, 1H), 7.10 (m, 3H), 7.25 (m, 1H), 7.35 (m, 5H). LRMS m/z=555.3 (M+1)+. Found C, 62.50, H, 6.34, N, 9.98%; C29H35N4O5Cl requires C, 62.75, H, 6.36, N, 10.09%.

Workup

  1. temperatureat reflux for 24 hr
  2. washwashed with water
  3. dry with materialdried over MgSO4
  4. customRemoval of the drying agent
  5. filtrationby filtration
  6. customfollowed by evaporation of the solvent
  7. customgave a red oil which
  8. customwas purified by chromatography (SiO2, gradient elution with 100% CH2Cl2; 99:1 CH2Cl2:MeOH; 98:2 CH2Cl2:MeOH)

Sources & evidence

ORD record
ord-7f0f8f459d1c4ae6b6409f6927cad00d
Source dataset
uspto-grants-2002_07
Patent number
US06417203B1

Reaction notes

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