Triethylamine → benzyl 2-[3-{[3-({2-[(tert-butoxycarbonyl)amino]ethoxy}methyl)phenethyl]amino}-5-chloro-6-methyl-2-oxo-1(2H)-pyrazinyl]acetate

HRID 2228776Notes

Reaction equation

HRID 2228776 reaction equation
[NH2:1][CH2:2][CH2:3][C:4]1[CH:5]=[C:6]([CH:19]=[CH:20][CH:21]=1)[CH2:7][O:8][CH2:9][CH2:10][NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15].[Cl:22][C:23]1[N:28]=[C:27](Cl)[C:26](=[O:30])[N:25]([CH2:31][C:32]([O:34][CH2:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)=[O:33])[C:24]=1[CH3:42].C(N(CC)CC)C>C(OCC)(=O)C>[C:14]([O:13][C:12]([NH:11][CH2:10][CH2:9][O:8][CH2:7][C:6]1[CH:5]=[C:4]([CH:21]=[CH:20][CH:19]=1)[CH2:3][CH2:2][NH:1][C:27]1[C:26](=[O:30])[N:25]([CH2:31][C:32]([O:34][CH2:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)=[O:33])[C:24]([CH3:42])=[C:23]([Cl:22])[N:28]=1)=[O:18])([CH3:17])([CH3:15])[CH3:16]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 10663926Benzyl 2-[3,5-dichloro-2-methyl-6-oxo-1(6H)-pyrazinyl]acetateHCID 18470932tert-Butyl 2-{[3-(2-aminoethyl)benzyl]oxy}ethylcarbamate

Product 1

HCID 18470846benzyl 2-[3-{[3-({2-[(tert-butoxycarbonyl)amino]ethoxy}methyl)phenethyl]amino}-5-chloro-6-methyl-2-oxo-1(2H)-pyrazinyl]acetateYield 45.1%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

A mixture of tert-butyl 2-{[3-(2-aminoethyl)benzyl]oxy}ethylcarbamate (preparation 105) (270 mg, 0.92 mmol), benzyl 2-[3,5-dichloro-2-methyl-6-oxo-1(6H)-pyrazinyl]acetate (preparation 17) (300 mg, 0.92 mmol), and triethylamine (140 ml, 1.01 mmol) in ethyl acetate was heated under reflux overnight. The cooled suspension was diluted with ethyl acetate, then washed with hydrochloric acid (2N), NaHCO3 solution, brine, then dried over MgSO4 and evaporated under reduced pressure. The crude product was purified by column chromatography on silica gel using ethyl acetate:pentane (40:60) as eluant, and triturated with ether, to give the title compound as a white solid, (243 mg, 45%). Re-purifiing the ether filtrate by column chromatography on silica gel provided an additional (176 mg, 33%) of the desired product.

Workup

  1. temperaturewas heated
  2. temperatureunder reflux overnight
  3. washwashed with hydrochloric acid (2N), NaHCO3 solution, brine
  4. dry with materialdried over MgSO4
  5. customevaporated under reduced pressure
  6. customThe crude product was purified by column chromatography on silica gel
  7. customtriturated with ether

Sources & evidence

ORD record
ord-39347fd1f2bf42a3a4492d94af73e421
Source dataset
uspto-grants-2002_07
Patent number
US06417203B1

Reaction notes

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