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Hydrochloric Acid → 1-{[1-(1-Ethyl-propyl)-2-thiophen-2-ylmethyl-1H-benzimidazole-5-carbonyl]-amino}-cycloheptanecarboxylic acid methyl ester

HRID 1750163
ノート
印刷プレビュー

反応式

HRID 1750163 の反応式
[CH2:1]([CH:3]([N:6]1[C:10]2[CH:11]=[CH:12][C:13]([C:15](O)=[O:16])=[CH:14][C:9]=2[N:8]=[C:7]1[CH2:18][C:19]1[S:20][CH:21]=[CH:22][CH:23]=1)[CH2:4][CH3:5])[CH3:2].C1C=NC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.Cl.[NH2:44][C:45]1([C:52]([O:54][CH3:55])=[O:53])[CH2:51][CH2:50][CH2:49][CH2:48][CH2:47][CH2:46]1.Cl>CN(C=O)C.O.C(Cl)CCl>[CH3:55][O:54][C:52]([C:45]1([NH:44][C:15]([C:13]2[CH:12]=[CH:11][C:10]3[N:6]([CH:3]([CH2:1][CH3:2])[CH2:4][CH3:5])[C:7]([CH2:18][C:19]4[S:20][CH:21]=[CH:22][CH:23]=4)=[N:8][C:9]=3[CH:14]=2)=[O:16])[CH2:51][CH2:50][CH2:49][CH2:48][CH2:47][CH2:46]1)=[O:53]
参加物実験手順後処理出典と根拠反応ノート

参加物

9

反応物 5

HCID 313Hydrochloric AcidHCID 81531Diisopropylethylamine2 回HCID 181649HOAtHCID 42614177Methyl 1-aminocycloheptane-1-carboxylate hydrochlorideHCID 867143731-(1-ethyl-propyl)-2-thiophen-2-ylmethyl-1H-benzoimidazole-5-carboxylic acid

生成物 1

HCID 86714372
1-{[1-(1-Ethyl-propyl)-2-thiophen-2-ylmethyl-1H-benzimidazole-5-carbonyl]-amino}-cycloheptanecarboxylic acid methyl ester
収率 86.2%

試薬・触媒・溶媒 3

HCID 111,2-Dichloroethane溶媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

To a solution of 160 mg of 1-(1-ethyl-propyl)-2-thiophen-2-ylmethyl-1H-benzoimidazole-5-carboxylic acid (The preparation of intermediates is described below) in 3 ml of dry DMF 73 mg of HOAT, 131 mg of EDC and 0.16 ml of DIPEA were added at 0° C. After 15 min 100 mg of methyl 1-amino-cycloheptanecarboxylate-hydrochloride and 0.16 ml of DIPEA were added and the reaction was stirred at it for 16 h. The reaction was then poured into water and the pH was adjusted to 3 by the addition of 2 M aqueous hydrochloric acid. The reaction was extracted with ethyl acetate three times. The combined organic phases were washed with saturated aqueous sodium bicarbonate solution and brine, dried over magnesium sulphate and concentrated. The crude product was purified by HPLC to yield 200 mg (85%) of 1-{[1-(1-Ethyl-propyl)-2-thiophen-2-ylmethyl-1H-benzimidazole-5-carbonyl]-amino}-cycloheptanecarboxylic acid methyl ester.

後処理

  1. additionwere added at 0° C
  2. extractionThe reaction was extracted with ethyl acetate three times
  3. washThe combined organic phases were washed with saturated aqueous sodium bicarbonate solution and brine
  4. dry with materialdried over magnesium sulphate
  5. concentrationconcentrated
  6. customThe crude product was purified by HPLC

出典と根拠

ORDレコード
ord-58c2a66162b94c7d830468af5a8c3aae
出典データセット
uspto-grants-2015_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09156796B2

反応ノート

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このページの内容参加物実験手順後処理出典と根拠反応ノート