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Diisopropylethylamine → N-[1-(2,3-dichlorobenzyl)pyrrolidin-3-(RS)-ylmethyl]-3-[5-(4-methoxyphenyl)pyrimidin-2-yl]propionamide Hydrochloride Salt

HRID 1276363
ノート
印刷プレビュー

反応式

HRID 1276363 の反応式
[ClH:1].C[N:3]([CH3:12])[CH2:4][CH2:5][CH2:6][N:7]=[C:8]=[N:9][CH2:10]C.[CH3:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[CH:26]=CN=C(CCC(O)=O)N=2)=[CH:17][CH:16]=1.[NH2:32][CH2:33][CH:34]1[CH2:38][CH2:37][N:36]([CH2:39][C:40]2[CH:45]=[CH:44][CH:43]=[C:42]([Cl:46])[C:41]=2[Cl:47])[CH2:35]1.[OH2:48].O[N:50]1[C:54]2[CH:55]=[CH:56][CH:57]=[CH:58][C:53]=2N=N1.C(N(C(C)C)CC)(C)C>C(Cl)(Cl)Cl.C(OCC)(=O)C>[Cl:47][C:41]1[C:42]([Cl:46])=[CH:43][CH:44]=[CH:45][C:40]=1[CH2:39][N:36]1[CH2:37][CH2:38][CH:34]([CH2:33][NH:32][C:58](=[O:48])[CH2:53][CH2:54][C:8]2[N:7]=[CH:6][C:5]([C:4]3[CH:19]=[CH:20][C:15]([O:14][CH3:13])=[CH:16][CH:17]=3)=[CH:10][N:9]=2)[CH2:35]1.[ClH:1].[Cl:47][C:41]1[C:42]([Cl:46])=[CH:43][CH:44]=[CH:45][C:40]=1[CH2:39][N:36]1[CH2:37][CH2:38][CH:34]([CH2:33][NH:32][C:57](=[O:48])[CH2:56][CH2:55][C:54]2[N:50]=[CH:26][C:21]([C:18]3[CH:17]=[CH:16][C:15]([O:14][CH3:13])=[CH:20][CH:19]=3)=[CH:12][N:3]=2)[CH2:35]1
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 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 114368453-(RS)-aminomethyl-1-(2,3-dichlorobenzyl)-pyrrolidineHCID 185455503-[4-(4-Methoxyphenyl)pyrimidin-2-yl]-propanoic acid

生成物 2

HCID 9828589
N-[1-(2,3-dichlorobenzyl)pyrrolidin-3-(RS)-ylmethyl]-3-[5-(4-methoxyphenyl)pyrimidin-2-yl]propionamide Hydrochloride Salt
収率 69%
HCID 9828590N-(1-(2,3-dichlorobenzyl)-pyrrolidin-3-(RS)-ylmethyl)-3-(5-(4-methoxyphenyl)pyrimidin-2-yl)propionamide

試薬・触媒・溶媒 2

HCID 6212Chloroform溶媒HCID 8857Ethyl Acetate溶媒

実験手順

1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.29 g, 1.5 mmol, 1.5 equiv.) was added to a suspension of 3-[4-(4-methoxyphenyl)pyrimidin-2-yl]-propanoic acid (0.26 g, 1.0 mmol, 1.0 equiv.), 3-(RS)-aminomethyl-1-(2,3-dichlorobenzyl)-pyrrolidine (0.26 g, 1.0 mmol), 1-hydroxybenzotriazole hydrate (0.20 g, 1.5 mmol, 1.5 equiv.), and diisopropylethylamine (0.44 mL, 2.5 mmol, 2.5 equiv.) in chloroform (2 mL). After stirring overnight at room temperature, the reaction mixture was diluted with ethyl acetate, washed sequentially with 1 M sodium hydroxide, water, 1 M hydrochloric acid, water and brine, then dried over sodium sulfate and concentrated. The residue was purified by flash chromatography (0→10% methanol in methylene chloride). Clean fractions containing the desired product were combined and concentrated, diluted with dioxane and treated with 4 M HCl (0.2 mL) in dioxane. The solution was concentrated under high vacuum to give N-(1-(2,3-dichlorobenzyl)-pyrrolidin-3-(RS)-ylmethyl)-3-(5-(4-methoxyphenyl)pyrimidin-2-yl)propionamide as the HCl salt (185 mg).

後処理

  1. washwashed sequentially with 1 M sodium hydroxide, water, 1 M hydrochloric acid, water and brine
  2. dry with materialdried over sodium sulfate
  3. concentrationconcentrated
  4. customThe residue was purified by flash chromatography (0→10% methanol in methylene chloride)
  5. additionClean fractions containing the desired product
  6. concentrationconcentrated
  7. additiondiluted with dioxane
  8. additiontreated with 4 M HCl (0.2 mL) in dioxane
  9. concentrationThe solution was concentrated under high vacuum

出典と根拠

ORDレコード
ord-2cab1368e1bc492188f69efe857f73bb
出典データセット
uspto-grants-2000_12
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US06166015

反応ノート

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