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

HRID 1097541ノート

反応式

HRID 1097541 の反応式
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

参加物

7

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
60 °C

実験手順

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, GH), 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.

後処理

  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

出典と根拠

ORDレコード
ord-5a03474349454e19a293340918d1687e
出典データセット
uspto-grants-2012_03
特許番号
US08143244B2

反応ノート

読み込み中…