Sodium Carbonate → 11-cyclohexyl-N-[(dimethylamino)sulfonyl]-6-hydroxy-8-methoxy-6H-isoindolo[2,1-a]indole-3-carboxamide

HRID 1453371Notes

Reaction equation

HRID 1453371 reaction equation
Br[C:2]1[NH:3][C:4]2[C:9]([C:10]=1[CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)=[CH:8][CH:7]=[C:6]([C:17]([NH:19][S:20]([N:23]([CH3:25])[CH3:24])(=[O:22])=[O:21])=[O:18])[CH:5]=2.[CH3:26][O:27][C:28]1[CH:33]=[CH:32][C:31](B(O)O)=[C:30]([CH:37]=[O:38])[CH:29]=1.[Li+].[Cl-].C([O-])([O-])=O.[Na+].[Na+]>CCO.C1(C)C=CC=CC=1.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>[CH:11]1([C:10]2[C:9]3[C:4](=[CH:5][C:6]([C:17]([NH:19][S:20]([N:23]([CH3:24])[CH3:25])(=[O:22])=[O:21])=[O:18])=[CH:7][CH:8]=3)[N:3]3[CH:37]([OH:38])[C:30]4[C:31]([C:2]=23)=[CH:32][CH:33]=[C:28]([O:27][CH3:26])[CH:29]=4)[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16]1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 27343652-Formyl-4-methoxybenzeneboronic acidHCID 587651502-bromo-3-cyclohexyl-N-(dimethylsulfamoyl)-1H-indole-6-carboxamide

Product 1

HCID 5968212111-cyclohexyl-N-[(dimethylamino)sulfonyl]-6-hydroxy-8-methoxy-6H-isoindolo[2,1-a]indole-3-carboxamide

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 21863594Toluene ethanolSolvent

Conditions

Temperature
85 °C

Procedure

To a slurried solution of 2-bromo-3-cyclohexyl-N-[(dimethylamino)sulfonyl]-indole-6-carboxamide (4.3 g, 10 mmol), 4-methoxy-2-formylphenylboronic acid (2.5 g, 14 mmol) and LiCl (1.05 g, 25 mmol) in EtOH/toluene (1:1, 80 mL) was added Pd(PPh3)4 (1.12 g, 1.0 mmol) and then 1M Na2CO3 (aq.) (30 mL, 30 mmol). The reaction solution was flushed with nitrogen and heated at 85° C. for 18 h and cooled to rt. The reaction was diluted with EtOAc (200 mL), washed with 0.5N aqueous HCl (100 mL) and brine (50 mL), dried (MgSO4), filtered and concentrated to yield 11-cyclohexyl-N-[(dimethylamino)sulfonyl]-6-hydroxy-8-methoxy-6H-isoindolo[2,1-a]indole-3-carboxamide which was used without further purification. LCMS: m/e 482 (M−H)−, ret time 1.63 min, column A, 2 minute gradient.

Workup

  1. customThe reaction solution was flushed with nitrogen
  2. temperaturecooled to rt
  3. additionThe reaction was diluted with EtOAc (200 mL)
  4. washwashed with 0.5N aqueous HCl (100 mL) and brine (50 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-a082102a81c745289c8aef5241fad610
Source dataset
uspto-grants-2009_01
Patent number
US07473688B2

Reaction notes

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