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

HRID 493974

Reaction equation

HRID 493974 reaction equation
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

Participants

11

Reactant 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

Product 1

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

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

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%.

Workup

  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.)

Sources & evidence

ORD record
ord-69055df68b064944b4396c22e73fcc1d
Source dataset
uspto-grants-2009_05
Patent number
US07538103B2

Linked notes

Loading…