Triethylamine → (S)-9-Chloro-5-[p-tert-butoxycarbonylaminomethyl-o-(2-methoxycarbonylethyl) phenylcarbamoylmethyl]-6,7-dihydro-1H, 5H-pyrido[1,2,3-de]quinoxaline-2,3-dione

HRID 862583Notes

Reaction equation

HRID 862583 reaction equation
[CH3:1][O:2][C:3]([CH2:5][CH2:6][C:7]1[CH:13]=[C:12]([CH2:14][NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH:11]=[CH:10][C:8]=1[NH2:9])=[O:4].[Cl:23][C:24]1[CH:25]=[C:26]2[CH2:38][CH2:37][C@@H:36]([CH2:39][C:40](O)=[O:41])[N:28]3[C:29](=[O:35])[C:30](=[O:34])[NH:31][C:32]([CH:33]=1)=[C:27]23.C(N(CC)CC)C.C1N(P(Cl)(N2C(=O)OCC2)=O)C(=O)OC1>ClCCl.C(OCC)(=O)C>[Cl:23][C:24]1[CH:25]=[C:26]2[CH2:38][CH2:37][C@@H:36]([CH2:39][C:40](=[O:41])[NH:9][C:8]3[CH:10]=[CH:11][C:12]([CH2:14][NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[CH:13][C:7]=3[CH2:6][CH2:5][C:3]([O:2][CH3:1])=[O:4])[N:28]3[C:29](=[O:35])[C:30](=[O:34])[NH:31][C:32]([CH:33]=1)=[C:27]23

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 19698388HCID 19698388, compoundHCID 131720478(S)-9-chloro-5-carboxymethyl-6,7-dihydro-1H, 5H-pyrido[1,2,3-de]quinoxaline-2,3-dione

Product 1

HCID 131720483(S)-9-Chloro-5-[p-tert-butoxycarbonylaminomethyl-o-(2-methoxycarbonylethyl) phenylcarbamoylmethyl]-6,7-dihydro-1H, 5H-pyrido[1,2,3-de]quinoxaline-2,3-dioneYield 57.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 2-(2-methoxycarbonylethyl)-4-tert-butoxycarbonylaminomethylaniline (3.4 g), (S)-9-chloro-5-carboxymethyl-6,7-dihydro-1H, 5H-pyrido[1,2,3-de]quinoxaline-2,3-dione (2.80 g, 9.5 mmol), triethylamine (2.43 g, 24 mmol), and Bop-Cl (2.42 g, 9.5 mmol) in dichloromethane (40 mL) was stirred for 2 h at room temperature and diluted with ethyl acetate (800 mL). The mixture was washed with 5% potassium hydrogen sulfate, water, 1/15 phosphate buffer (pH 7.5), water, and brine, successively, dried over magnesium sulfate, and concentrated. The residue was recrystallized from acetone-ethyl acetate to give 3.22 g of the title compound. The mother liquid was concentrated and the residue was purified by silica gel column chromatography with ethyl acetate to 1% AcOH/ethyl acetate to give additionally 0.8 g of the title compound (72%).

Workup

  1. washThe mixture was washed with 5% potassium hydrogen sulfate, water, 1/15 phosphate buffer (pH 7.5), water, and brine
  2. dry with materialsuccessively, dried over magnesium sulfate
  3. concentrationconcentrated
  4. customThe residue was recrystallized from acetone-ethyl acetate

Sources & evidence

ORD record
ord-4d71eceef39043ac9042dc164304056f
Source dataset
uspto-grants-1998_02
Patent number
US05719152

Reaction notes

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