Triethylamine → HCID 57835289, compound

HRID 731123Notes

Reaction equation

HRID 731123 reaction equation
[CH3:1][C:2]([CH3:15])([O:4][C:5]([NH:7][C:8]1([C:12](O)=O)[CH2:11][CH2:10][CH2:9]1)=[O:6])[CH3:3].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(CC)CC.[CH3:45][O:46][C:47](=[O:58])[C:48]1[CH:53]=[C:52]([NH:54][CH3:55])[C:51]([NH2:56])=[CH:50][C:49]=1[CH3:57]>C(Cl)Cl>[CH3:45][O:46][C:47]([C:48]1[C:49]([CH3:57])=[CH:50][C:51]2[N:56]=[C:12]([C:8]3([NH:7][C:5]([O:4][C:2]([CH3:15])([CH3:3])[CH3:1])=[O:6])[CH2:11][CH2:10][CH2:9]3)[N:54]([CH3:55])[C:52]=2[CH:53]=1)=[O:58]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 1512646Cyclobutanecarboxylic acid, 1-(((1,1-dimethylethoxy)carbonyl)amino)-HCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 57835240HCID 57835240, compound

Product 1

HCID 57835289HCID 57835289, compoundYield 58.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

1-((1,1-Dimethylethoxycarbonyl)amino)cyclobutanecarboxylic acid (1.40 g, 6.5 mmol) was dissolved in CH2Cl2 (45 mL) and reacted with TBTU in the presence of Et3N for a period of 30 min to pre-activate the acid. A solution of 4-amino-2-methyl-5-(methylamino)benzoic acid methyl ester 6-8 from Example 6 (1.33 g, 6.85 mmol) in CH2Cl2 (10 mL) was added slowly over a period of 30 min and stirring of the reaction mixture was continued for 20 h. The reaction mixture was concentrated to dryness, and the residue was re-dissolved in AcOH (10.0 mL) and stirred at 70° C. for 2 h to achieve cyclization of the benzimidazole ring. The reaction mixture was concentrated to dryness and the residue was dissolved in EtOAc (˜250 mL), extracted with aqueous saturated NaHCO3 (2×100 mL) and brine (100 mL). The organic layer was dried over anhydrous MgSO4 and evaporated to dryness. The residue was purified by flash column chromatography (using a solvent gradient from 40% to 50% EtOAc in hexane) to obtain the pure 2-(1-tert-butoxycarbonylaminocyclobutyl)-3,6-dimethyl-3H-benzoimidazole-5-carboxylic acid methyl ester 7-1 as a beige solid (1.41 g, 55% yield) and recover some of the unreacted diamino starting material.

Workup

  1. concentrationThe reaction mixture was concentrated to dryness
  2. dissolutionthe residue was re-dissolved in AcOH (10.0 mL)
  3. stirringstirred at 70° C. for 2 h
  4. concentrationThe reaction mixture was concentrated to dryness
  5. dissolutionthe residue was dissolved in EtOAc (˜250 mL)
  6. extractionextracted with aqueous saturated NaHCO3 (2×100 mL) and brine (100 mL)
  7. dry with materialThe organic layer was dried over anhydrous MgSO4
  8. customevaporated to dryness
  9. customThe residue was purified by flash column chromatography (

Sources & evidence

ORD record
ord-41fad53e05844fea865e043979fd805f
Source dataset
uspto-grants-2009_09
Patent number
US07582770B2

Reaction notes

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