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

HRID 1097540

Reaktionsgleichung

Reaktionsgleichung von HRID 1097540
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

Komponenten

11

Edukt 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

Produkt 1

HCID 597500763-cyclohexyl-N-(N,N-dimethylsulfamoyl)-2-(2-formyl-4-methoxyphenyl)-1H-indole-6-carboxamideAusbeute 64,9 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 702EthanolLösungsmittelHCID 962WaterLösungsmittelHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

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-brorno-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%.

Aufarbeitung

  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.)

Quellen und Nachweise

ORD-Eintrag
ord-60c439d52ab448d4b122b34c82a5f75d
Quelldatensatz
uspto-grants-2012_03
Patentnummer
US08143244B2

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