Hydrochloric Acid → 3-cyclohexyl-N-(N,N-dimethylsulfamoyl)-2-(2-formyl-4-methoxyphenyl)-1H-indole-6-carboxamide

HRID 272293

反応式

HRID 272293 の反応式
C1C=C(C(N)=O)C=C2C=1C=C1C3C(=CC=CC=3)CN12.Br[C:21]1[NH:22][C:23]2[C:28]([C:29]=1[CH:30]1[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1)=[CH:27][CH:26]=[C:25]([C:36]([NH:38][S:39](=[O:44])(=[O:43])[N:40]([CH3:42])[CH3:41])=[O:37])[CH:24]=2.[CH:45]([C:47]1[CH:52]=[C:51]([O:53][CH3:54])[CH:50]=[CH:49][C:48]=1B(O)O)=[O:46].[Li+].[Cl-].C([O-])([O-])=O.[Na+].[Na+].Cl>O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCO.C1(C)C=CC=CC=1>[CH:30]1([C:29]2[C:28]3[C:23](=[CH:24][C:25]([C:36]([NH:38][S:39](=[O:44])(=[O:43])[N:40]([CH3:42])[CH3:41])=[O:37])=[CH:26][CH:27]=3)[NH:22][C:21]=2[C:48]2[CH:49]=[CH:50][C:51]([O:53][CH3:54])=[CH:52][C:47]=2[CH:45]=[O:46])[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1

参加物

11

反応物 6

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 27343652-Formyl-4-methoxybenzeneboronic acidHCID 587651502-bromo-3-cyclohexyl-N-(dimethylsulfamoyl)-1H-indole-6-carboxamideHCID 665886926H-isoindolo[2,1-a]indole-3-carboxamide

生成物 1

HCID 597500763-cyclohexyl-N-(N,N-dimethylsulfamoyl)-2-(2-formyl-4-methoxyphenyl)-1H-indole-6-carboxamide収率 64.9%

試薬・触媒・溶媒 4

HCID 178418397HCID 178418397、化合物触媒HCID 702Ethanol溶媒HCID 962Water溶媒HCID 1140Toluene溶媒

反応条件

温度
70 °C

実験手順

6H-Isoindolo[2,1-a]indole-3-carboxamide, 11-cyclohexyl-N-[(dimethylamino)sulfonyl]-6-ethoxy-8-methoxy-. To a 5 L four necked round bottom flask equipped with a temperature controller, a condenser, a N2 inlet and a mechanical stirrer, was charged toluene (900 mL), EtOH (900 mL), 2-bromo-3-cyclohexyl-N-(N,N-dimethylsulfamoyl)-1H-indole-6-carboxamide (90 g, 0.21 mol), 2-formyl-4-methoxyphenylboronic acid (49.2 g, 0.273 mol) and LiCl (22.1 g, 0.525 mol). The resulting solution was bubbled with N2 for 15 mins. A solution of Na2CO3 (66.8 g, 0.63 mol) in H2O (675 mL) was added and the reaction mixture was bubbled with N2 for another (10 mins). Pd(PPh3)4 (7.0 g, 6.3 mmol) was added and the reaction mixture was heated to 70° C. for 20 h. After cooling to 35° C., a solution of 1 N HCl (1.5 L) was added slowly. The resulting mixture was transferred to a 6 L separatory funnel and extracted with EtOAc (2×1.5 L). The combined organic extracts were washed with brine (2 L), dried over MgSO4, filtered and concentrated in vacuo to give a yellow solid, which was triturated with 20% EtOAc in hexane (450 mL, 50° C. to 0° C.) to give 3-cyclohexyl-N-(N,N-dimethylsulfamoyl)-2-(2-formyl-4-methoxyphenyl)-1H-indole-6-carboxamide(65.9 g) as a yellow solid. HPLC purity, 98%.

後処理

  1. customThe resulting solution was bubbled with N2 for 15 mins
  2. customthe reaction mixture was bubbled with N2 for another (10 mins)
  3. temperatureAfter cooling to 35° C.
  4. customThe resulting mixture was transferred to a 6 L separatory funnel
  5. extractionextracted with EtOAc (2×1.5 L)
  6. washThe combined organic extracts were washed with brine (2 L)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto give a yellow solid, which
  11. customwas triturated with 20% EtOAc in hexane (450 mL, 50° C. to 0° C.)

出典と根拠

ORDレコード
ord-85a0725f9e5942d285bb0aee63d483dd
出典データセット
uspto-grants-2008_11
特許番号
US07456166B2

関連ノート

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