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

HRID 1091557노트

반응식

HRID 1091557 반응식
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

참가 물질

7

반응물 4

HCID 313Hydrochloric AcidHCID 10796Cesium carbonate2회HCID 3016938Methyl 2-(dimethoxyphosphinyl)acrylate2회HCID 5968212111-cyclohexyl-N-[(dimethylamino)sulfonyl]-6-hydroxy-8-methoxy-6H-isoindolo[2,1-a]indole-3-carboxamide

생성물 1

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

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

반응 조건

온도
60 °C

실험 절차

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. 1H NMR (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.

후처리

  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

출처 및 근거

ORD 기록
ord-969d2f1ada894b90b77d8a19fa4d2b1c
출처 데이터셋
uspto-grants-2012_03
특허 번호
US08129367B2

반응 노트

불러오는 중…