Methanol → 4-(2,3-Dihydro-2-oxo-1H-benzimidazol-1-yl)-1-piperidineacetic acid

HRID 1611425ノート

反応式

HRID 1611425 の反応式
[O:1]=[C:2]1[N:6]([CH:7]2[CH2:12][CH2:11][N:10]([CH2:13][C:14]([O:16]CC)=[O:15])[CH2:9][CH2:8]2)[C:5]2[CH:19]=[CH:20][CH:21]=[CH:22][C:4]=2[NH:3]1.[OH-].[Na+].CO>C(O)(=O)C>[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:19]=[CH:20][CH:21]=[CH:22][C:4]=2[NH:3]1

参加物

5

反応物 3

HCID 887MethanolHCID 14798Sodium HydroxideHCID 20750053HCID 20750053、化合物

生成物 1

HCID 220370584-(2,3-Dihydro-2-oxo-1H-benzimidazol-1-yl)-1-piperidineacetic acid

試薬・触媒・溶媒 1

HCID 176Acetic Acid溶媒

実験手順

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).

出典と根拠

ORDレコード
ord-cbfb051ecca345d29715a2a423223de8
出典データセット
uspto-grants-2006_01
特許番号
US06987188B2

反応ノート

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