Diphosgene → {5-Fluoro-4-[2-methyl-4-(2,3,4,5-tetrahydrobenzo[b]azepine-1-carbonyl)-benzylcarbamoyl]-2-oxo-3,4-dihydro-2H-quinoxalin-1-yl}acetic Acid Tert-Butyl Ester

HRID 558956Notes

Reaction equation

HRID 558956 reaction equation
[C:1]([O:5][C:6](=[O:20])[CH2:7][N:8]1[C:17]2[C:12](=[C:13]([F:18])[CH:14]=[CH:15][CH:16]=2)[NH:11][CH2:10][C:9]1=[O:19])([CH3:4])([CH3:3])[CH3:2].ClC([O:24][C:25](Cl)(Cl)Cl)=O.C(N(C(C)C)CC)(C)C.[NH2:38][CH2:39][C:40]1[CH:45]=[CH:44][C:43]([C:46]([N:48]2[CH2:54][CH2:53][CH2:52][CH2:51][C:50]3[CH:55]=[CH:56][CH:57]=[CH:58][C:49]2=3)=[O:47])=[CH:42][C:41]=1[CH3:59]>C1(C)C=CC=CC=1.C1COCC1>[C:1]([O:5][C:6](=[O:20])[CH2:7][N:8]1[C:17]2[C:12](=[C:13]([F:18])[CH:14]=[CH:15][CH:16]=2)[N:11]([C:25](=[O:24])[NH:38][CH2:39][C:40]2[CH:45]=[CH:44][C:43]([C:46]([N:48]3[CH2:54][CH2:53][CH2:52][CH2:51][C:50]4[CH:55]=[CH:56][CH:57]=[CH:58][C:49]3=4)=[O:47])=[CH:42][C:41]=2[CH3:59])[CH2:10][C:9]1=[O:19])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 10426DiphosgeneHCID 81531DiisopropylethylamineHCID 15896086(4-(Aminomethyl)-3-methylphenyl)(2,3,4,5-tetrahydro-1H-benzo[b]azepin-1-yl)methanoneHCID 57470781(5-Fluoro-2-oxo-3,4-dihydro-2H-quinoxalin-1-yl)acetic acid tert-butyl ester

Product 1

HCID 59807173{5-Fluoro-4-[2-methyl-4-(2,3,4,5-tetrahydrobenzo[b]azepine-1-carbonyl)-benzylcarbamoyl]-2-oxo-3,4-dihydro-2H-quinoxalin-1-yl}acetic Acid Tert-Butyl Ester

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (5-fluoro-2-oxo-3,4-dihydro-2H-quinoxalin-1-yl)acetic acid tert-butyl ester from Example 7A (84 mg, 0.30 mmol) in toluene (4.0 ml) were added trichloromethyl chloroformate (36 μl, 0.30 mmol), diisopropylethylamine (54 μl, 0.30 mmol) and a spatula full of activated carbon. The mixture was heated at reflux for 2 h, cooled, filtered through Celite®, washed with EtOAc and evaporated in vacuo. The residue was taken up in THF (3.0 ml) and added to a solution of (4-aminomethyl-3-methylphenyl)-(2,3,4,5-tetrahydrobenzo[b]azepin-1-yl)methanone from Example F (85 mg, 0.29 mmol) in THF (3.0 ml) while cooling in an ice/water bath. The mixture was allowed to warm to room temperature, stirred for 1 h and evaporated in vacuo. The residue was purified by flash chromatography on silica (eluant EtOAc:pet. ether 75:25) to afford a white solid; yield 120 mg, 66%.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 2 h
  3. temperaturecooled
  4. filtrationfiltered through Celite®
  5. washwashed with EtOAc
  6. customevaporated in vacuo
  7. temperaturewhile cooling in an ice/water bath
  8. customevaporated in vacuo
  9. customThe residue was purified by flash chromatography on silica (eluant EtOAc:pet. ether 75:25)
  10. customto afford a white solid

Sources & evidence

ORD record
ord-fa034ab1458e4a149760f524e94f87fd
Source dataset
uspto-grants-2011_11
Patent number
US08063038B2

Reaction notes

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