Hydrochloric Acid → HCID 25128173, compound

HRID 1747421Notes

Reaction equation

HRID 1747421 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[C:6]([CH3:11])[CH:7]=[CH:8][CH:9]=2)[C:4]([CH2:12][N:13]2[C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=3[N:15]([CH:22]([CH2:27][O:28][CH3:29])[CH2:23][C:24]([OH:26])=O)[C:14]2=[O:30])=[CH:3]1.C1N=CN(C(N2C=NC=C2)=O)C=1.[CH3:43][N:44]1[CH:48]=[C:47]([S:49]([NH2:52])(=[O:51])=[O:50])[N:46]=[CH:45]1.C1CCN2C(=NCCC2)CC1.Cl>O.C1COCC1>[CH3:1][N:2]1[C:10]2[C:5](=[C:6]([CH3:11])[CH:7]=[CH:8][CH:9]=2)[C:4]([CH2:12][N:13]2[C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=3[N:15]([CH:22]([CH2:27][O:28][CH3:29])[CH2:23][C:24]([NH:52][S:49]([C:47]3[N:46]=[CH:45][N:44]([CH3:43])[CH:48]=3)(=[O:51])=[O:50])=[O:26])[C:14]2=[O:30])=[CH:3]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 27368851-methyl-1H-imidazole-4-sulfonamideHCID 59497401HCID 59497401, compound

Product 1

HCID 25128173HCID 25128173, compoundYield 41.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
55 °C

Procedure

3-[3-(1,4-Dimethyl-1H-indol-3-ylmethyl)-2-oxo-2,3-dihydro-benzimidazol-1-yl]-4-methoxy-butyric acid (30 mg, 0.074 mmol) is dissolved THF (0.70 mL) and CDI (27 mg, 0.17 mmol) is added into it at room temperature. The mixture is heated at 55° C. for 1 hr. After the mixture is cooled down to room temperature, 1-Methyl-1H-imidazole-4-sulfonic acid amide (24 mg, 0.15 mmol) is added and after 10 min, DBU (0.022 mL, 0.15 mmol) is added. The mixture is stirred for 16 hr at room temperature. 2.0 mL of 1.0 M HCl is added followed by 20 mL of water. The mixture is extracted with EtOAc (3×25 mL) and the organic layers are combined, dried and concentrated to give crude product. Purification by flash column chromatography affords 17 mg (41%) of 1-Methyl-1H-imidazole-4-sulfonic acid {3-[3-(1,4-dimethyl-1H-indol-3-ylmethyl)-2-oxo-2,3-dihydro-benzimidazol-1-yl]-4-methoxy-butyryl}-amide. LCMS (ESMS): m/z 551.25 (M+H+).

Workup

  1. additionis added into it at room temperature
  2. temperatureAfter the mixture is cooled down to room temperature
  3. extractionThe mixture is extracted with EtOAc (3×25 mL)
  4. customdried
  5. concentrationconcentrated
  6. customto give crude product
  7. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-69ad2dd11f9e4bd9a574a472af46e76b
Source dataset
uspto-grants-2015_10
Patent number
US09150556B2

Reaction notes

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