Diisopropylethylamine → 1-(2-Aminoethyl)-3-[(5-chlorothien-2-yl)sulfonyl]-1,3-dihydro-2H-benzimidazol-2-one

HRID 1984540Notes

Reaction equation

HRID 1984540 reaction equation
C(OC(=O)[NH:7][CH2:8][CH2:9][N:10]1[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[NH:12][C:11]1=[O:19])(C)(C)C.[Cl:21][C:22]1[S:26][C:25]([S:27](Cl)(=[O:29])=[O:28])=[CH:24][CH:23]=1.C(N(C(C)C)CC)(C)C>C1COCC1.CN(C)C1C=CN=CC=1>[NH2:7][CH2:8][CH2:9][N:10]1[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[N:12]([S:27]([C:25]2[S:26][C:22]([Cl:21])=[CH:23][CH:24]=2)(=[O:29])=[O:28])[C:11]1=[O:19]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 27339255-Chlorothiophene-2-sulfonyl chlorideHCID 57428815tert-Butyl 2-(2-oxo-2,3-dihydrobenzo[d]imidazol-1-yl)ethylcarbamate

Product 1

HCID 114738001-(2-Aminoethyl)-3-[(5-chlorothien-2-yl)sulfonyl]-1,3-dihydro-2H-benzimidazol-2-one

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A solution of [2-(2-oxo-2,3-dihydrobenzimidazol-1-yl)ethyl]carbamic acid t-butyl ester (27 mg, 0.1 mmol) in THF at room temperature is treated with (5-chlorothien-2-yl)sulfonyl chloride (26 mg, 0.12 mmol) followed by diisopropylethylamine (25 uL, 0.2 mmol) and 4-dimethylaminopyridine (5 mg), stirred at room temperature for 16 h and concentrated in vacuo. The resultant residue is dissolved in THF, treated with HCl in dioxane (4 N) (1 mL), stirred for 4 h and concentrated in vacuo. This residue is dissolved in a mixture of DMSO, methanol and water and purified by Gilson1 preparative HPLC to give the title product, 10 mg, [M+H] 358, retention time (RT) 2.18 minutes. 1Gilson Preparative HPLC conditions: Gilson Preparative HPLC system; YMC Pro C18, 20 mm×50 mm ID, 5 uM column; 2 mL injection; Solvent A: 0.02% TFA/water; Solvent B:0.02% TFA/acetonitrile; Gradient: Time 0: 95% A; 2 min: 95% A; 14 min: 10% A, 15 min: 10% A, 16 min: 95% A; Flow rate 22.5 mL/min; Detection: 254 nm DAD.

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe resultant residue is dissolved in THF
  3. additiontreated with HCl in dioxane (4 N) (1 mL)
  4. stirringstirred for 4 h
  5. concentrationconcentrated in vacuo
  6. dissolutionThis residue is dissolved in a mixture of DMSO, methanol and water
  7. custompurified by Gilson1 preparative HPLC

Sources & evidence

ORD record
ord-d0874477eef841f59e49ff614fb613b8
Source dataset
uspto-grants-2009_06
Patent number
US07544701B2

Reaction notes

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