1,8-Diazabicyclo(5.4.0)undec-7-ene → 2-bromo-3-cyclohexyl-N-(dimethylsulfamoyl)-1H-indole-6-carboxamide

HRID 1453370Notes

Reaction equation

HRID 1453370 reaction equation
C(C1NC=CN=1)(C1NC=CN=1)=O.[Br:13][C:14]1[NH:15][C:16]2[C:21]([C:22]=1[CH:23]1[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1)=[CH:20][CH:19]=[C:18]([C:29]([OH:31])=O)[CH:17]=2.[CH3:32][N:33]([CH3:38])[S:34]([NH2:37])(=[O:36])=[O:35].C1CCN2C(=NCCC2)CC1>C1COCC1.CCOC(C)=O>[Br:13][C:14]1[NH:15][C:16]2[C:21]([C:22]=1[CH:23]1[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1)=[CH:20][CH:19]=[C:18]([C:29]([NH:37][S:34]([N:33]([CH3:38])[CH3:32])(=[O:36])=[O:35])=[O:31])[CH:17]=2

Participants

7

Reactant 4

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 134472N,N-DimethylsulfamideHCID 5142612-bromo-3-cyclohexyl-1H-indole-6-carboxylic acidHCID 5250894Bis-(1H-imidazol-2-YL)-methanone

Product 1

HCID 587651502-bromo-3-cyclohexyl-N-(dimethylsulfamoyl)-1H-indole-6-carboxamideYield 46%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

Carbonyl diimidazole (6.0 g, 37 mmol) was added to a solution of 2-bromo-3-cyclohexyl-1H-indole-6-carboxylic acid (10 g, 31 mmol) in THF (30 mL) and the reaction was stirred at 50° C. for 2 h (a white precipitate had formed). The reaction was cooled to rt and treated with N,N-dimethylsulfamide (4.6 g, 37 mmol). Then DBU (6.7 mL) in THF (20 mL) was added dropwise and the reaction was stirred at rt overnight. The solution was diluted with EtOAc (300 mL) and washed with H2O (150 mL), 1N aqueous HCl (2×100 mL) and brine (100 mL). The combined aqueous layers were extracted with EtOAc (200 mL) and the organic layer was washed with 1N aqueous HCl (150 mL) and brine (50 mL). The combined organic layers were dried (MgSO4), filtered and concentrated to an oil. The oil was diluted with Et2O and concentrated to a semi-solid which was triturated with Et2O to yield 2-bromo-3-cyclohexyl-N-[(dimethylamino)sulfonyl]-indole-6-carboxamide (6.1 g, 14 mmol, 46%) as a light yellow solid. The organic washes where concentrated and purified by silica gel chromatography (20-35% EtOAc/hexanes) to yield additional 2-bromo-3-cyclohexyl-N-[(dimethylamino)sulfonyl]-indole-6-carboxamide (2.5 g, 6 mmol, 19%). 1HNMR (500 MHz, CD3OD) δ 7.90 (d, J=1.8 Hz, 1H), 7.77 (d, J=8.5 Hz, 1H), 7.56 (dd, J=1.8, 8.5 Hz, 1H), 3.01 (s, 6H), 2.93-2.86 (m, 1H), 2.04-1.76 (m, 7H), 1.54-1.37 (m, 3H). LCMS: m/e 426 (M−H)−, ret time 1.55 min, column A, 2 minute gradient.

Workup

  1. customhad formed)
  2. temperatureThe reaction was cooled to rt
  3. stirringthe reaction was stirred at rt overnight
  4. washwashed with H2O (150 mL), 1N aqueous HCl (2×100 mL) and brine (100 mL)
  5. extractionThe combined aqueous layers were extracted with EtOAc (200 mL)
  6. washthe organic layer was washed with 1N aqueous HCl (150 mL) and brine (50 mL)
  7. dry with materialThe combined organic layers were dried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated to an oil
  10. additionThe oil was diluted with Et2O
  11. concentrationconcentrated to a semi-solid which
  12. customwas triturated with Et2O

Sources & evidence

ORD record
ord-91c600c6225b4814885870d88261a582
Source dataset
uspto-grants-2009_01
Patent number
US07473688B2

Reaction notes

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