1-Hydroxybenzotriazole → (3'S)-1'-[4-(1H-Benzimidazol-2-ylmethyl)benzoyl]-1,3'-bipyrrolidine

HRID 1163092Notes

Reaction equation

HRID 1163092 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH2:10][C:11]1[CH:19]=[CH:18][C:14]([C:15]([OH:17])=O)=[CH:13][CH:12]=1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.[N:42]1([C@H:47]2[CH2:51][CH2:50][NH:49][CH2:48]2)[CH2:46][CH2:45][CH2:44][CH2:43]1>CN(C=O)C>[NH:3]1[C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=2[N:1]=[C:2]1[CH2:10][C:11]1[CH:12]=[CH:13][C:14]([C:15]([N:49]2[CH2:50][CH2:51][C@H:47]([N:42]3[CH2:46][CH2:45][CH2:44][CH2:43]3)[CH2:48]2)=[O:17])=[CH:18][CH:19]=1

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 7176274(3S)-3-(Pyrrolidin-1-YL)pyrrolidineHCID 190232394-((1H-benzo[d]imidazol-2-yl)methyl)benzoic acid

Product 1

HCID 58970760(3'S)-1'-[4-(1H-Benzimidazol-2-ylmethyl)benzoyl]-1,3'-bipyrrolidineYield 73%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of methyl 4-((1H-benzo[d]imidazol-2-yl)methyl)benzoate (400 mg, 1.5 mmol) in methanol was treated with aqueous sodium hydroxide (2.5 M, 3.75 mmol), heated at reflux temperature for 3 h and concentrated in vacuo. The resultant residue was dispersed in water and acidified with excess formic acid. The resultant precipitate was removed by filtration, washed with water and dried under vacuum overnight to provide 4-((1H-benzo[d]imidazol-2-yl)methyl)benzoic acid (92%) as a white solid, [M+H] 253.2. A solution of 4-((1H-benzo[d]imidazol-2-yl)methyl)benzoic acid (200 mg, 0.79 mmol) in DMF was treated with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (183 mg, 0.952 mmol) and 1-hydroxybenzotriazole (134 mg, 0.873 mmol), stirred at room temperature for 3 h, treated with a solution of (3′S)-1,3′-bipyrrolidine (166.6 mg, 1.19 mmol) in DMF, stirred at room temperature for 6 h and concenrated in vacuo. This residue was partitioned between aqueous potassium carbonate (1.0 M) and dichloromethane. The organic phase was washed with water, dried over sodium sulfate and concentrated under reduced pressure. Purification of the concentrate by flash column chromatography (silica, dichloromethane:methanol 20:1 to 10:1) afforded the title compound (73%), identified by mass spectral analysis. [M+H] 253.2.

Workup

  1. stirringstirred at room temperature for 6 h
  2. customThis residue was partitioned between aqueous potassium carbonate (1.0 M) and dichloromethane
  3. washThe organic phase was washed with water
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customPurification of the
  7. concentrationconcentrate by flash column chromatography (silica, dichloromethane:methanol 20:1 to 10:1)

Sources & evidence

ORD record
ord-f7cfe6b42bf34c2896414d7c51190706
Source dataset
uspto-grants-2010_10
Patent number
US07820825B2

Reaction notes

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