Hydrochloric Acid → N-{3-Ethoxy-3-[3-(4-methyl-benzo[b]thiophen-3-ylmethyl)-2-oxo-2,3-dihydro-benzimidazol-1-yl]-propionyl}-benzenesulfonamide

HRID 1747339Notes

Reaction equation

HRID 1747339 reaction equation
[CH2:1]([O:3][CH:4]([N:9]1[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=2[N:11]([CH2:18][C:19]2[C:20]3[C:27]([CH3:28])=[CH:26][CH:25]=[CH:24][C:21]=3[S:22][CH:23]=2)[C:10]1=[O:29])[CH2:5][C:6](O)=[O:7])[CH3:2].C(N1C=CN=C1)(N1C=CN=C1)=O.[C:42]1([S:48]([NH2:51])(=[O:50])=[O:49])[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1.N12CCCN=C1CCCCC2.Cl>C1COCC1.O>[CH2:1]([O:3][CH:4]([N:9]1[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=2[N:11]([CH2:18][C:19]2[C:20]3[C:27]([CH3:28])=[CH:26][CH:25]=[CH:24][C:21]=3[S:22][CH:23]=2)[C:10]1=[O:29])[CH2:5][C:6]([NH:51][S:48]([C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)(=[O:50])=[O:49])=[O:7])[CH3:2]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 7370BenzenesulfonamideHCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 251278473-Ethoxy-3-[3-(4-methyl-benzo[b]thiophen-3-ylmethyl)-2-oxo-2,3-dihydro-benzimidazol-1-yl]-propionic acid

Product 1

HCID 25126877N-{3-Ethoxy-3-[3-(4-methyl-benzo[b]thiophen-3-ylmethyl)-2-oxo-2,3-dihydro-benzimidazol-1-yl]-propionyl}-benzenesulfonamideYield 36.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
55 °C

Procedure

3-Ethoxy-3-[3-(4-methyl-benzo[b]thiophen-3-ylmethyl)-2-oxo-2,3-dihydro-benzimidazol-1-yl]-propionic acid (45 mg, 0.11 mmol) is dissolved in dry THF (1.0 mL) and 1,1′-carbonyl diimidazole (40 mg, 0.25 mmol) is added into it at room temperature. The mixture is stirred for 30 min and then it is heated at 55° C. for 1 hr. After the mixture is cooled down to room temperature, benzenesulfonamide (34 mg, 0.22 mmol) is added and after 10 min, 1,8-diazabicyclo[5,4,0]undec-7-ene (0.033 mL, 0.22 mmol) is added. The mixture is stirred for 4 hr at room temperature and 1.0 M HCl solution (3 mL) is added followed by water (30 mL). The mixture is extracted with EtOAc (3×50 mL) and the organic layers are combined, dried and concentrated to give crude product. Purification by preparative TLC using 6% MeOH in CH2Cl2 with 1.0% concentrated aqueous NH4OH solution (28%) affords 22 mg (36%) of N-{3-Ethoxy-3-[3-(4-methyl-benzo[b]thiophen-3-ylmethyl)-2-oxo-2,3-dihydro-benzimidazol-1-yl]-propionyl}-benzenesulfonamide. LCMS (ESMS): m/z 550.15 (M+H+).

Workup

  1. temperatureAfter the mixture is cooled down to room temperature
  2. stirringThe mixture is stirred for 4 hr at room temperature
  3. extractionThe mixture is extracted with EtOAc (3×50 mL)
  4. customdried
  5. concentrationconcentrated
  6. customto give crude product
  7. customPurification by preparative TLC

Sources & evidence

ORD record
ord-68bd72acb4ee4c639ffc4a08a64c75ba
Source dataset
uspto-grants-2015_10
Patent number
US09150556B2

Reaction notes

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