Diphosgene → {1-[4-(5H,11H-Benzo[e]pyrrolo[1,2-a][1,4]diazepine-10-carbonyl)-2-methylbenzylcarbamoyl]-8-fluoro-2,3-dihydro-1H-quinolin-4-ylidene}acetic acid ethyl ester

HRID 558953Notes

Reaction equation

HRID 558953 reaction equation
[CH2:1]([O:3][C:4](=[O:17])[CH:5]=[C:6]1[C:15]2[C:10](=[C:11]([F:16])[CH:12]=[CH:13][CH:14]=2)[NH:9][CH2:8][CH2:7]1)[CH3:2].ClC([O:21][C:22](Cl)(Cl)Cl)=O.C(N(C(C)C)CC)(C)C.[NH2:35][CH2:36][C:37]1[CH:42]=[CH:41][C:40]([C:43]([N:45]2[C:51]3[CH:52]=[CH:53][CH:54]=[CH:55][C:50]=3[CH2:49][N:48]3[CH:56]=[CH:57][CH:58]=[C:47]3[CH2:46]2)=[O:44])=[CH:39][C:38]=1[CH3:59]>C1(C)C=CC=CC=1.ClCCl.CCOC(C)=O>[CH2:1]([O:3][C:4](=[O:17])[CH:5]=[C:6]1[C:15]2[C:10](=[C:11]([F:16])[CH:12]=[CH:13][CH:14]=2)[N:9]([C:22](=[O:21])[NH:35][CH2:36][C:37]2[CH:42]=[CH:41][C:40]([C:43]([N:45]3[C:51]4[CH:52]=[CH:53][CH:54]=[CH:55][C:50]=4[CH2:49][N:48]4[CH:56]=[CH:57][CH:58]=[C:47]4[CH2:46]3)=[O:44])=[CH:39][C:38]=2[CH3:59])[CH2:8][CH2:7]1)[CH3:2]

Participants

8

Reactant 4

HCID 10426DiphosgeneHCID 81531Diisopropylethylamine2×HCID 25178381(4-aminomethyl-3-methylphenyl)-(5H,11H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-10-yl)methanoneHCID 67000179(8-fluoro-2,3-dihydro-1H-quinolin-4-ylidene)acetic acid ethyl ester

Product 1

HCID 67000028{1-[4-(5H,11H-Benzo[e]pyrrolo[1,2-a][1,4]diazepine-10-carbonyl)-2-methylbenzylcarbamoyl]-8-fluoro-2,3-dihydro-1H-quinolin-4-ylidene}acetic acid ethyl ester

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of (8-fluoro-2,3-dihydro-1H-quinolin-4-ylidene)acetic acid ethyl ester from Example 4A (50 mg, 0.21 mmol), trichioromethyl chloroformate (28 μl, 0.23 mmol), diisopropylethylamine (41 μl, 0.23 mmol) and a small spatula of activated carbon in toluene (2 ml) was heated at reflux for 2 h. After cooling, EtOAc was added and the mixture filtered through Celite® and evaporated. The residue was taken up in THF to which was added a solution of (4-aminomethyl-3-methylphenyl)-(5H,11H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-10-yl)methanone from Example G (77 mg, 0.23 mmol) and diisopropylethylamine (41 μl, 0.23 mmol) in dichloromethane (2 ml). The mixture was stirred for 18 h, evaporated and the residue was purified by flash chromatography on silica (EtOAC:pet ether, 20:80 to 50:50) to give a white solid, yield 4 mg (3%).

Workup

  1. temperatureat reflux for 2 h
  2. temperatureAfter cooling
  3. filtrationthe mixture filtered through Celite®
  4. customevaporated
  5. customevaporated
  6. customthe residue was purified by flash chromatography on silica (EtOAC:pet ether, 20:80 to 50:50)
  7. customto give a white solid, yield 4 mg (3%)

Sources & evidence

ORD record
ord-a6b40ce34aa14f3ab7985b743dcd6572
Source dataset
uspto-grants-2011_11
Patent number
US08063038B2

Reaction notes

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