Toluene → 4-Cyanomethyl-8-fluoro-3-oxo-3,4-dihydro-2H-quinoxaline-1-carboxylic acid 2-methyl-4-(2,3,4,5-tetrahydrobenzo[b]azepine-1-carbonyl)benzylamide

HRID 558968Notes

Reaction equation

HRID 558968 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:15])[N:7]2[CH2:12][C:13]#[N:14].[C:16](Cl)(Cl)=[O:17].C1(C)C=CC=CC=1.C(N(C(C)C)CC)(C)C.[NH2:36][CH2:37][C:38]1[CH:43]=[CH:42][C:41]([C:44]([N:46]2[CH2:52][CH2:51][CH2:50][CH2:49][C:48]3[CH:53]=[CH:54][CH:55]=[CH:56][C:47]2=3)=[O:45])=[CH:40][C:39]=1[CH3:57]>C1COCC1>[CH3:57][C:39]1[CH:40]=[C:41]([C:44]([N:46]2[CH2:52][CH2:51][CH2:50][CH2:49][C:48]3[CH:53]=[CH:54][CH:55]=[CH:56][C:47]2=3)=[O:45])[CH:42]=[CH:43][C:38]=1[CH2:37][NH:36][C:16]([N:4]1[C:3]2[C:8](=[CH:9][CH:10]=[CH:11][C:2]=2[F:1])[N:7]([CH2:12][C:13]#[N:14])[C:6](=[O:15])[CH2:5]1)=[O:17]

Participants

7

Reactant 5

HCID 1140TolueneHCID 6371PhosgeneHCID 81531Diisopropylethylamine2×HCID 15896086(4-(Aminomethyl)-3-methylphenyl)(2,3,4,5-tetrahydro-1H-benzo[b]azepin-1-yl)methanoneHCID 23111114(5-Fluoro-2-oxo-3,4-dihydro-2H-quinoxalin-1-yl)acetonitrile

Product 1

HCID 115844924-Cyanomethyl-8-fluoro-3-oxo-3,4-dihydro-2H-quinoxaline-1-carboxylic acid 2-methyl-4-(2,3,4,5-tetrahydrobenzo[b]azepine-1-carbonyl)benzylamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of (5-fluoro-2-oxo-3,4-dihydro-2H-quinoxalin-1-yl)acetonitrile from Example 13A (183 mg, 0.89 mmol) in THF (2 ml) were added a solution of phosgene in toluene (20%, 0.61 ml, 1.2 mmol) and diisopropylethylamine (200 μl, 1.2 mmol). The mixture was stirred for 2 h. To the mixture were added a solution of (4-aminomethyl-3-methylphenyl)-(2,3,4,5-tetrahydrobenzo[b]azepin-1-yl)methanone from Example F (260 mg, 0.89 mmol) in THF (2 ml) and diisopropylethylamine (155 μl, 0.89 mmol). The mixture was stirred for 2 h and evaporated in vacuo. The residue was purified by flash column chromatography on silica (eluant EtOAc:pet. ether 80:20 to EtOAc 100%) to give a white solid; yield 268 mg, 57%.

Workup

  1. stirringThe mixture was stirred for 2 h
  2. customevaporated in vacuo
  3. customThe residue was purified by flash column chromatography on silica (eluant EtOAc:pet. ether 80:20 to EtOAc 100%)
  4. customto give a white solid

Sources & evidence

ORD record
ord-9d4f0adc2d9c4e179ec65e9e6d1e3b4e
Source dataset
uspto-grants-2011_11
Patent number
US08063038B2

Reaction notes

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