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

HRID 862594Notes

Reaction equation

HRID 862594 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[CH:16]=[CH:15][C:13]([NH2:14])=[C:12]([O:17][CH2:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH:11]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:26][C:27]1[CH:28]=[C:29]2[CH2:41][CH2:40][C@@H:39]([CH2:42][C:43](O)=[O:44])[N:31]3[C:32](=[O:38])[C:33](=[O:37])[NH:34][C:35]([CH:36]=1)=[C:30]23.C1N(P(Cl)(N2C(=O)OCC2)=O)C(=O)OC1.C(N(CC)CC)C>ClCCl.C(OCC)(=O)C>[Cl:26][C:27]1[CH:28]=[C:29]2[CH2:41][CH2:40][C@@H:39]([CH2:42][C:43](=[O:44])[NH:14][C:13]3[CH:15]=[CH:16][C:10]([CH2:9][NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])=[CH:11][C:12]=3[O:17][CH2:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[N:31]3[C:32](=[O:38])[C:33](=[O:37])[NH:34][C:35]([CH:36]=1)=[C:30]23

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 196983594-tert-Butoxycarbonylaminomethyl-2-tert-butoxycarbonylmethoxyanilineHCID 131720478(S)-9-chloro-5-carboxymethyl-6,7-dihydro-1H, 5H-pyrido[1,2,3-de]quinoxaline-2,3-dione

Product 1

HCID 131720491(S)-9-Chloro-5-[p-tert-butoxycarbonylaminomethyl-o-(tert-butoxycarbonylmethoxy) phenylcarbamoylmethyl]-6,7-dihydro-1H, 5H-pyrido[1,2,3-de]quinoxaline-2,3-dioneYield 63.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 4-tert-butoxycarbonylaminomethyl-2-tert-butoxycarbonylmethoxyaniline (930 mg, 2.61 mmol), (S)-9-chloro-5-carboxymethyl-6,7-dihydro-1H, 5H-pyrido[1,2,3-de]quinoxaline-2,3-dione (807 mg, 2.74 mmol), Bop-Cl (770 mg, 2.99 mmol), and triethylamine (2 mL) in dichloromethane (20 mL) was stirred for 4 days at room temperature. The mixture was diluted with ethyl acetate (500 mL) and washed with 5% aqueous potassium hydrogen sulfate, water, phosphate buffer (pH 7.5), water, and brine, successively, dried over magnesium sulfate, and concentrated. The residual solid was recrystallized from acetone-ethyl acetate to give 1.04 g of the title compound. The mother liquid was concentrated and the residue was purified by silica gel column chromatography with 0.3% acetic acid/ethyl acetate to give additionally 360 mg of the title compound. A total amount of 1.40 g of the title compound was obtained (85%).

Workup

  1. washwashed with 5% aqueous potassium hydrogen sulfate, water, phosphate buffer (pH 7.5), water, and brine
  2. dry with materialsuccessively, dried over magnesium sulfate
  3. concentrationconcentrated
  4. customThe residual solid was recrystallized from acetone-ethyl acetate

Sources & evidence

ORD record
ord-c9d6fa79d9124064b864eeaf3024c712
Source dataset
uspto-grants-1998_02
Patent number
US05719152

Reaction notes

Loading…