Ethyl bromoacetate → HCID 20750053, compound

HRID 1760185Notes

Reaction equation

HRID 1760185 reaction equation
[O:1]=[C:2]1[N:6]([CH:7]2[CH2:12][CH2:11][N:10]([CH2:13][C:14]([OH:16])=[O:15])[CH2:9][CH2:8]2)[C:5]2[CH:17]=[CH:18][CH:19]=[CH:20][C:4]=2[NH:3]1.O=C1N(C2CCNCC2)[C:25]2C=CC=C[C:24]=2N1.BrCC(OCC)=O.C(N(C(C)C)CC)(C)C>C(#N)C>[O:1]=[C:2]1[N:6]([CH:7]2[CH2:12][CH2:11][N:10]([CH2:13][C:14]([O:16][CH2:24][CH3:25])=[O:15])[CH2:9][CH2:8]2)[C:5]2[CH:17]=[CH:18][CH:19]=[CH:20][C:4]=2[NH:3]1

Participants

6

Reactant 4

HCID 7748Ethyl bromoacetateHCID 81531DiisopropylethylamineHCID 886381,3-Dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-oneHCID 220370584-(2,3-Dihydro-2-oxo-1H-benzimidazol-1-yl)-1-piperidineacetic acid

Product 1

HCID 20750053HCID 20750053, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Compounds of formula A in which Z=2,3-dihydro-2-oxo-1H-benzimidazol-1-yl and L=(N-methylene)piperidin-4-yl are prepared from amidines (V) or (VI) and [4-(2-keto-1-benzimidazolinyl)piperidin-1-yl]acetic acid. For example, 4-(2-keto-1-benzimidazolinyl)piperidine is reacted with a bromoacetic acid ester, such as ethyl bromoacetate, in the presence of an amine base, such as diisopropylethylamine, in an inert solvent such as acetonitrile, at a temperature ranging from ambient temperature to reflux, to afford ethyl [4-(2-keto-1-benzimidazolinyl)piperidin-1-yl]acetate. This ester is subjected to hydrolysis under basic conditions, for example, by treatment with sodium hydroxide in an alcoholic solution such as aqueous methanol, to yield, upon acidification with an inorganic or organic acid such as hydrochloric or acetic acid for example, [4-(2-keto-1-benzimidazolinyl)piperidin-1-yl]acetic acid. This carboxylic acid is reacted directly with amidine (V) or (VI), in the presence of an amine base, under peptide coupling conditions described above, to afford amidino benzimidazolinones (XV) of formula A in which Y=carbonyl and L=(N-methylene)piperidin-4-yl (Scheme 5).

Workup

  1. customranging from ambient temperature
  2. temperatureto reflux

Sources & evidence

ORD record
ord-b810156bc3bb4c0e91ea60070ad1ab2f
Source dataset
uspto-grants-2005_01
Patent number
US06841552B1

Reaction notes

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