Hydrochloric Acid → methyl 7H-indolo[2,1-a][2]benzazepine-6-carboxylic acid

HRID 493975Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 493975
C1([C:7]2[C:15]3[C:10](=[CH:11][C:12](C(NS(N(C)C)(=O)=O)=O)=[CH:13][CH:14]=3)[N:9]3[CH:25](O)[C:26]4[C:31]([C:8]=23)=[CH:30][CH:29]=[C:28](OC)[CH:27]=4)CCCCC1.COP([C:41](=[CH2:46])[C:42](OC)=O)(OC)=O.[C:47](=[O:50])([O-])[O-:48].[Cs+].[Cs+].Cl>CN(C=O)C.O>[CH3:42][C:41]1[C:46]2[C:8]3=[CH:7][C:15]4[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=4[N:9]3[CH2:25][C:26]([C:47]([OH:48])=[O:50])=[CH:27][C:28]=2[CH:29]=[CH:30][CH:31]=1

Komponenten

7

Edukt 4

HCID 313Hydrochloric AcidHCID 10796Cesium carbonate2×HCID 3016938Methyl 2-(dimethoxyphosphinyl)acrylate2×HCID 5968212111-cyclohexyl-N-[(dimethylamino)sulfonyl]-6-hydroxy-8-methoxy-6H-isoindolo[2,1-a]indole-3-carboxamide

Produkt 1

HCID 66588728methyl 7H-indolo[2,1-a][2]benzazepine-6-carboxylic acid

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

A solution of 11-cyclohexyl-N-[(dimethylamino)sulfonyl]-6-hydroxy-8-methoxy-6H-isoindolo[2,1-a]indole-3-carboxamide (cyclic hemiaminal) (63.0 g, 130 mmol), methyl 2-(dimethoxyphosphoryl)acrylate (60 g, 261 mmol), cesium carbonate (106 g, 326 mmol) in DMF (400 mL) was heated at 60° C. (bath temp) for 4.5 h. Additional methyl 2-(dimethoxyphosphoryl)acrylate (15 g, 65 mmol) and cesium carbonate (21.2 g, 65 mmol) were added and the reaction was heated at 60° C. overnight then and cooled to rt. The stirring reaction mixture was diluted with H2O (1 L), slowly neutralized with 1N aqueous HCl (800 mL), stirred 3 h, and then the precipitates were collected by filtration. The solids were triturated with Et2O (800 mL) and dried to yield methyl 7H-indolo[2,1-a][2]benzazepine-6-carboxylic acid, 13-cyclohexyl-10-[[[(dimethylamino)sulfonyl]amino]carbonyl]-3-methoxy-, methyl ester (70.2 g, 127 mmol, 98%) as a yellow solid which was used without further purification. 1HNMR (300 MHz, CDCl3) δ 8.67 (s, 1H), 8.09 (s, 1H), 7.86 (d, J=8.4 Hz, 1H), 7.80 (s, 1H), 7.50 (d, J=8.4 Hz, 1H), 7.42 (d, J=8.8 Hz, 1H), 7.08 (dd, J=2.6, 8.8 Hz, 1H), 6.98 (d, J=2.6 Hz, 1H), 5.75-5.51 (m, 1H), 4.29-4.01 (m, 1H), 3.89 (s, 3H), 3.82 (s, 3H), 3.05 (s, 6H), 2.87-2.73 (m, 1H), 2.11-1.12 (m, 10H). LCMS: m/e 550 (M−H)−, ret time 3.21 min, column A, 4 minute gradient.

Aufarbeitung

  1. temperaturecooled to rt
  2. customThe stirring reaction mixture
  3. filtrationthe precipitates were collected by filtration
  4. customThe solids were triturated with Et2O (800 mL)
  5. customdried

Quellen und Nachweise

ORD-Eintrag
ord-a18b9666e60a496e99a039390d65fcb9
Quelldatensatz
uspto-grants-2009_05
Patentnummer
US07538103B2

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