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

HRID 862576Notes

Reaction equation

HRID 862576 reaction equation
C[NH:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][NH:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[CH:5][C:4]=1[CH2:18][C:19]([O:21][CH3:22])=[O:20].[Cl:23][C:24]1[CH:25]=[C:26]2[CH2:38][CH2:37][C@@H:36]([CH2:39][C:40]([OH:42])=O)[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:42])[NH:2][C:3]3[CH:8]=[CH:7][C:6]([CH2:9][NH:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[CH:5][C:4]=3[CH2:18][C:19]([O:21][CH3:22])=[O:20])[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 54494100Methyl 4-tert-butoxycarbonylaminomethyl-2-methoxycarbonylmethylanilineHCID 131720478(S)-9-chloro-5-carboxymethyl-6,7-dihydro-1H, 5H-pyrido[1,2,3-de]quinoxaline-2,3-dione

Product 1

HCID 131720477(S)-9-Chloro-5-[p-tert-butoxycarbonylaminomethyl-o-(methoxycarbonylmethyl)phenylcarbamoylmethyl]-6,7-dihydro-1H, 5H-pyrido[1,2,3-de]-quinoxaline-2,3-dioneYield 74.6%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of methyl 4-tert-butoxycarbonylaminomethyl-2-methoxycarbonylmethylaniline (1.20 g, 4.27 mmol), (S)-9-chloro-5-carboxymethyl-6,7-dihydro-1H, 5H-pyrido[1,2,3-de]quinoxaline-2,3-dione (1.26 g, 4.27 mmol), triethylamine (1.49 mL, 10.7 mmol), and Bop-Cl (1.19 g, 4.69 mmol) in dichloromethane (26 mL) was stirred for 4.5 h at 0° C. to room temperature and diluted with ethyl acetate. The mixture was washed successively with 5% potassium hydrogen sulfate, water, 1/15 phosphate buffer (pH 7.5), water, and brine, dried over magnesium sulfate, and concentrated. The residual solid was washed with a 1:1 mixture of diethyl ether and dichloromethane, and dried to give 1.82 g of the title compound (74%).

Workup

  1. washThe mixture was washed successively with 5% potassium hydrogen sulfate, water, 1/15 phosphate buffer (pH 7.5), water, and brine
  2. dry with materialdried over magnesium sulfate
  3. concentrationconcentrated
  4. washThe residual solid was washed with a 1:1 mixture of diethyl ether and dichloromethane
  5. customdried

Sources & evidence

ORD record
ord-feb28235dd0a49a1b56dbee5090e54d1
Source dataset
uspto-grants-1998_02
Patent number
US05719152

Reaction notes

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