Hydrochloric Acid → methyl 11-cyclohexyl-6-hydroxy-6H-isoindolo[2,1-a]indole-3-carboxylate

HRID 272547ノート

反応式

HRID 272547 の反応式
C1[C:11]2[C:10]3=[CH:12][C:13]4[CH:14]=[CH:15][C:16](C(N)=O)=[CH:17][C:18]=4[N:9]3[CH2:8][CH:7]=[CH:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.[OH-:22].[Na+].Cl.[C:25](Cl)(=[O:29])[C:26](Cl)=O.CCN(P1(N(C)CCCN1C)=NC(C)(C)C)CC.CNS(NC)(=O)=O.[CH3:56]O.[CH2:58]1[CH2:62][O:61][CH2:60][CH2:59]1>C(Cl)Cl>[CH:13]1([C:12]2[C:7]3[C:8](=[CH:56][C:58]([C:62]([O:61][CH3:60])=[O:22])=[CH:59][CH:6]=3)[N:9]3[CH:25]([OH:29])[C:26]4[C:11]([C:10]=23)=[CH:5][CH:4]=[CH:3][CH:2]=4)[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1

参加物

9

反応物 7

HCID 313Hydrochloric Acid2 回HCID 14798Sodium HydroxideHCID 65578Oxalyl chlorideHCID 89736N,N'-DimethylsulfamideHCID 35138512-((1,1-Dimethylethyl)imino)-N,N-diethylhexahydro-1,3-dimethyl-2lambda5-1,3,2-diazaphosphorin-2-amineHCID 21899815MeOH tetrahydrofuranHCID 666396907H-indolo[2,1-a][2]benzazepine-10-carboxamide

生成物 1

HCID 11552259methyl 11-cyclohexyl-6-hydroxy-6H-isoindolo[2,1-a]indole-3-carboxylate収率 69%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

反応条件

温度
22 °C

実験手順

7H-Indolo[2,1-a][2]benzazepine-10-carboxamide, 13-cyclohexyl-N-[(dimethylamino)sulfonyl]-6-(ethylsulfonyl)-To a solution of 7H-Indolo[2,1-a][2]benzazepine-10-carboxylic acid,13-cyclohexyl-6-(ethylsulfonyl)-, methyl ester (80 mg, 0.17 mmol) in 1:1 MeOH/THF (2.0 mL) was added 1M NaOH (2.0 mL). The resulting mixture was stirred at 22° C. for 16 hr. 1M HCl (15 mL) was added and the aqueous layer was extracted with CHCl3 (2×15 mL). The organic phase was dried over Na2SO4, filtered, and concentrated under reduced pressure to afford a white solid. This solid was dissolved in CH2Cl2 (1.5 mL) and 2M oxalyl chloride (1.5 mL) in CH2Cl2 was added. This solution was stirred at 22° C. for 2 hr and concentrated under reduced pressure. The resulting yellow oil was redissolved in CH2Cl2 (1.5 mL); BEMP (94 mg, 0.34 mmol) and dimethylsulfamide (107 mg, 0.86 mmol) were added. The resulting mixture was allowed to stir at 22° C. for 6 hr 1M HCl (15 mL) was added and the aqueous layer was extracted with CHCl3 (2×30 mL). The organic phase was concentrated under reduced pressure. This oil was purified by reverse-phase prep HPLC to afford the title compound (67 mg, 69%) as a yellow paste. MS m/z 556 (MH+). 1H NMR (300 MHz, CDCl3) δ ppm 1.18-1.70 (m, 5H), 1.35 (t, 3H), 1.77 (m, 2H), 1.87-2.16 (m, 3H), 2.88 (m, 1H), 3.08 (s, 6H), 3.15 (q, 2H), 4.18 (broad m, 1H), 5.67 (broad m, 1H), 7.38 (s, 1H), 7.47 (m, 2H), 7.51 (dd, J=7.6, 8.4 Hz,1H), 7.61 (d, J=7.6 Hz, 1H), 7.75 (d, J=8.4 Hz, 1H), 7.87 (d, J=8.4 Hz, 1H), 8.31 (s, 1H), 8.54 (broad s, 1H).

後処理

  1. extractionthe aqueous layer was extracted with CHCl3 (2×15 mL)
  2. dry with materialThe organic phase was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customto afford a white solid
  6. stirringThis solution was stirred at 22° C. for 2 hr
  7. concentrationconcentrated under reduced pressure
  8. dissolutionThe resulting yellow oil was redissolved in CH2Cl2 (1.5 mL)
  9. additionwas added
  10. extractionthe aqueous layer was extracted with CHCl3 (2×30 mL)
  11. concentrationThe organic phase was concentrated under reduced pressure
  12. customThis oil was purified by reverse-phase prep HPLC

出典と根拠

ORDレコード
ord-3a1ca0f6ebf147c1b3192badac7ad711
出典データセット
uspto-grants-2008_11
特許番号
US07456167B2

反応ノート

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