Diphosgene → 8-Fluoro-4-(2-methoxyethyl)-3-oxo-3,4-dihydro-2H-quinoxaline-1-carboxylic acid 4-(5H,11H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-10-carbonyl)-2-methylbenzylamide

HRID 558973Notes

Reaction equation

HRID 558973 reaction equation
[F:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[NH:4][CH2:5][C:6](=[O:16])[N:7]2[CH2:12][CH2:13][O:14][CH3:15].ClC([O:20][C:21](Cl)(Cl)Cl)=O.C(N(C(C)C)CC)(C)C.[NH2:34][CH2:35][C:36]1[CH:41]=[CH:40][C:39]([C:42]([N:44]2[C:50]3[CH:51]=[CH:52][CH:53]=[CH:54][C:49]=3[CH2:48][N:47]3[CH:55]=[CH:56][CH:57]=[C:46]3[CH2:45]2)=[O:43])=[CH:38][C:37]=1[CH3:58]>C1(C)C=CC=CC=1.C1COCC1>[CH:57]1[CH:56]=[CH:55][N:47]2[CH2:48][C:49]3[CH:54]=[CH:53][CH:52]=[CH:51][C:50]=3[N:44]([C:42]([C:39]3[CH:40]=[CH:41][C:36]([CH2:35][NH:34][C:21]([N:4]4[C:3]5[C:8](=[CH:9][CH:10]=[CH:11][C:2]=5[F:1])[N:7]([CH2:12][CH2:13][O:14][CH3:15])[C:6](=[O:16])[CH2:5]4)=[O:20])=[C:37]([CH3:58])[CH:38]=3)=[O:43])[CH2:45][C:46]=12

Participants

7

Reactant 4

HCID 10426DiphosgeneHCID 81531Diisopropylethylamine2×HCID 231110975-Fluoro-1-(2-methoxyethyl)-3,4-dihydro-1H-quinoxalin-2-oneHCID 25178381(4-aminomethyl-3-methylphenyl)-(5H,11H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-10-yl)methanone

Product 1

HCID 115923158-Fluoro-4-(2-methoxyethyl)-3-oxo-3,4-dihydro-2H-quinoxaline-1-carboxylic acid 4-(5H,11H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-10-carbonyl)-2-methylbenzylamide

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-fluoro-1-(2-methoxyethyl)-3,4-dihydro-1H-quinoxalin-2-one from Example 16A (100 mg, 0.44 mmol) in toluene (7.0 ml) were added trichloromethyl chloroformate (54 μl, 0.45mmol), diisopropylethylamine (81 μl, 0.45 mmol) and a spatula full of activated carbon. The mixture was heated at reflux for 2 h. The mixture was cooled to room temperature, filtered through Celite® and evaporated. The residue was taken up in THF (5.0 ml) and added to a solution of (4-aminomethyl-3-methylphenyl)-(5H,11H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-10-yl)methanone from Example G (145 mg, 0.44 mmol) in THF (5.0 ml) and diisopropylethylamine (81 μl, 0.45 mmol) while cooling in an ice/water bath. The mixture was allowed to warm to room temperature, stirred for 18 h and evaporated in vacuo. The residue was purified by flash column chromatography on silica (eluant EtOAc:pet. ether 90:10) to give an off-white solid; yield 200 mg, 78%.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 2 h
  3. filtrationfiltered through Celite®
  4. customevaporated
  5. temperaturewhile cooling in an ice/water bath
  6. temperatureto warm to room temperature
  7. customevaporated in vacuo
  8. customThe residue was purified by flash column chromatography on silica (eluant EtOAc:pet. ether 90:10)
  9. customto give an off-white solid

Sources & evidence

ORD record
ord-2ebeab17ecba4a50b4ca342998d572ea
Source dataset
uspto-grants-2011_11
Patent number
US08063038B2

Reaction notes

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