1,1'-Carbonyldiimidazole → 3-[4-(1-(isopropylsulfonylaminocarbonyl)-1-(3,4-methylenedioxyphenyl)methoxy)-3,5-dipropylphenyl-methyl]-5,7-dimethyl-2-ethyl-3H-imidazo[4,5-b]pyridine

HRID 1741754

Reaction equation

HRID 1741754 reaction equation
[C:1]([CH:4]([C:32]1[CH:37]=[CH:36][C:35]2[O:38][CH2:39][O:40][C:34]=2[CH:33]=1)[O:5][C:6]1[C:11]([CH2:12][CH2:13][CH3:14])=[CH:10][C:9]([CH2:15][N:16]2[C:20]3=[N:21][C:22]([CH3:26])=[CH:23][C:24]([CH3:25])=[C:19]3[N:18]=[C:17]2[CH2:27][CH3:28])=[CH:8][C:7]=1[CH2:29][CH2:30][CH3:31])([OH:3])=O.C(N1C=CN=C1)(N1C=CN=C1)=O.[CH:53]([S:56]([NH2:59])(=[O:58])=[O:57])([CH3:55])[CH3:54].N12CCCN=C1CCCCC2>C1COCC1>[CH:53]([S:56]([NH:59][C:1]([CH:4]([C:32]1[CH:37]=[CH:36][C:35]2[O:38][CH2:39][O:40][C:34]=2[CH:33]=1)[O:5][C:6]1[C:11]([CH2:12][CH2:13][CH3:14])=[CH:10][C:9]([CH2:15][N:16]2[C:20]3=[N:21][C:22]([CH3:26])=[CH:23][C:24]([CH3:25])=[C:19]3[N:18]=[C:17]2[CH2:27][CH3:28])=[CH:8][C:7]=1[CH2:29][CH2:30][CH3:31])=[O:3])(=[O:58])=[O:57])([CH3:55])[CH3:54]

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 3549191Propane-2-sulfonamideHCID 19010493Benzo[1,3]dioxol-5-yl-[4-(2-ethyl-5,7-dimethyl-imidazo[4,5-b]pyridin-3-ylmethyl)-2,6-dipropyl-phenoxy]-acetic acid

Product 1

HCID 190104903-[4-(1-(isopropylsulfonylaminocarbonyl)-1-(3,4-methylenedioxyphenyl)methoxy)-3,5-dipropylphenyl-methyl]-5,7-dimethyl-2-ethyl-3H-imidazo[4,5-b]pyridineYield 27.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
80 °C

Procedure

A 15 mL capacity high pressure vessel equipped with a magnetic stir bar was charged with a solution of 0.230 g (0.42 mmol) of the product of Example 13 in 4.0 mL of anhydrous THF and 0.172 g (1.06 mmol) of 1,1'-carbonyldiimidazole was added. The vessel was sealed and the contents were stirred and heated at 80° C. for 4 hours. The reaction was then cooled to room temperature, opened and a solution of 0.130 g (1.06 mmol) of isopropylsulfonamide and 158 μL (1.06 mmol) of 1,8-diazabicyclo[5.4.0]undec-7-ene in 4 mL THF was added. The reaction vessel was resealed and then stirred and heated at 80° C. overnight. The reaction vessel was then cooled, opened and the contents were partitioned between water and EtOAc. The organic layer was separated washed with 10% aqueous NaHSO4, brine, dried (MgSO4), filtered and evaporated. The residual oil was purified on a silica gel flash chromatography column eluted first with 250 mL of CHCl3 /MeOH/NH4OH (95:5:0.5), next with 200 mL of CHCl3 /MeOH/NH4OH (92:8:0.5), and finally with 200 mL of CHCl3 /MeOH/NH4OH (90:10:0.5). Evaporation of the purified fractions and drying in vacuo afforded 0.074 g (27%) of the title compound.

Workup

  1. customA 15 mL capacity high pressure vessel equipped with a magnetic stir bar
  2. additionwas added
  3. customThe vessel was sealed
  4. temperatureThe reaction was then cooled to room temperature
  5. stirringstirred
  6. temperatureheated at 80° C. overnight
  7. temperatureThe reaction vessel was then cooled
  8. customthe contents were partitioned between water and EtOAc
  9. customThe organic layer was separated
  10. washwashed with 10% aqueous NaHSO4, brine
  11. dry with materialdried (MgSO4)
  12. filtrationfiltered
  13. customevaporated
  14. customThe residual oil was purified on a silica gel flash chromatography column
  15. washeluted first with 250 mL of CHCl3 /MeOH/NH4OH (95:5:0.5), next with 200 mL of CHCl3 /MeOH/NH4OH (92:8:0.5)
  16. customEvaporation of the purified fractions
  17. customdrying in vacuo

Sources & evidence

ORD record
ord-c95aa8f8bc4446cbb910a5eda27e787a
Source dataset
uspto-grants-1994_08
Patent number
US05334598

Linked notes

Loading…