Oxalyl chloride → 4,5-Dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid (2-chloro-4-methylcarbamoyl-phenyl)-methyl-amide

HRID 2078798

Reaktionsgleichung

Reaktionsgleichung von HRID 2078798
[N:1]1[C:10]2[C:9]3[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=3[O:7][CH2:6][CH2:5][C:4]=2[S:3][C:2]=1[C:15]([OH:17])=[O:16].[C:18](Cl)(=O)[C:19](Cl)=O.[Cl:24][C:25]1[CH:26]=[C:27]([CH:32]=[CH:33][C:34]=1[NH:35][CH3:36])[C:28]([NH:30][CH3:31])=[O:29].C(=O)(O)[O-].[Na+]>ClCCl.CN(C=O)C.C(#N)C>[CH2:18]([O:16][C:15]([C:2]1[S:3][C:4]2[CH2:5][CH2:6][O:7][C:8]3[CH:14]=[CH:13][CH:12]=[CH:11][C:9]=3[C:10]=2[N:1]=1)=[O:17])[CH3:19].[Cl:24][C:25]1[CH:26]=[C:27]([C:28](=[O:29])[NH:30][CH3:31])[CH:32]=[CH:33][C:34]=1[N:35]([CH3:36])[C:15]([C:2]1[S:3][C:4]2[CH2:5][CH2:6][O:7][C:8]3[CH:14]=[CH:13][CH:12]=[CH:11][C:9]=3[C:10]=2[N:1]=1)=[O:17]

Komponenten

9

Edukt 4

HCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 579002073-chloro-N-methyl-4-methylamino-benzamideHCID 866348394,5-Dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid

Produkt 2

HCID 442422284,5-Dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid (2-chloro-4-methylcarbamoyl-phenyl)-methyl-amideHCID 57900160[1]Benzoxepino[5,4-D]thiazole-2-carboxylic acid, 4,5-dihydro-, ethyl ester

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideKatalysatorHCID 6342AcetonitrileLösungsmittelHCID 6344DichloromethaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

4,5-Dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid ethyl ester was prepared according to Example 136 for 226, and hydrolyzed to the corresponding acid using General Procedure B. To a suspension of 4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid (130 mg) in dry dichloromethane (10 mL) was added oxalyl chloride (78 μL) and DMF (1 drop). After 1 hour the solvent was reduced in vacuo and the residue was dissolved in acetonitrile (10 mL) and to this was added 3-chloro-N-methyl-4-methylamino-benzamide from Example 21 (116 mg) and sodium bicarbonate (49 mg). The reaction mixture was warmed to 60° C. After 3 hours the reaction mixture was cooled, diluted with dichloromethane, washed with water, dried (MgSO4) and the solvent removed in vacuo. The residue was recrystallized form ethyl acetate/methanol/hexane to yield 121 (132 mg). NMR: (CDCl3): 3.04 (3H, d), 3.31 (2H, t), 3.48 (3H, s), 4.28-4.31 (2H, m), 6.05 (1H, sbr.), 6.81-6.83 (1H, m), 6.96 (1H, d), 7.05-7.15 (2H, m), 7.48 (1H, d), 7.78 (1H, dd), 7.93 (1H, s). MS: (ESI+) MH+ 428

Aufarbeitung

  1. temperatureAfter 3 hours the reaction mixture was cooled
  2. washwashed with water
  3. dry with materialdried (MgSO4)
  4. customthe solvent removed in vacuo
  5. customThe residue was recrystallized form ethyl acetate/methanol/hexane

Quellen und Nachweise

ORD-Eintrag
ord-eb6b7171ca19404c8d6b067f6f3d73cf
Quelldatensatz
uspto-grants-2011_04
Patentnummer
US07928248B2

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