1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → 2-((S)-2-{(R)-2-tert-butoxycarbonylamino-2-[4-((S)-2,2-dimethyl-[1,3]dioxolan4-ylmethoxy)-phenyl]-acetylamino}-3-phenyl-propionylamino)-thiazole-4-carboxylic acid methyl ester

HRID 2222978ノート

反応式

HRID 2222978 の反応式
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:13]1[CH:18]=[CH:17][C:16]([O:19][CH2:20][C@H:21]2[CH2:25][O:24][C:23]([CH3:27])([CH3:26])[O:22]2)=[CH:15][CH:14]=1)[C:10](O)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:28][O:29][C:30]([C:32]1[N:33]=[C:34]([NH:37][C:38](=[O:48])[C@@H:39]([NH2:47])[CH2:40][C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[S:35][CH:36]=1)=[O:31].Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1>ClCCl.C(OCC)(=O)C>[CH3:28][O:29][C:30]([C:32]1[N:33]=[C:34]([NH:37][C:38](=[O:48])[C@@H:39]([NH:47][C:10](=[O:11])[C@H:9]([NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:4])[CH3:3])=[O:7])[C:13]2[CH:18]=[CH:17][C:16]([O:19][CH2:20][C@H:21]3[CH2:25][O:24][C:23]([CH3:27])([CH3:26])[O:22]3)=[CH:15][CH:14]=2)[CH2:40][C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[S:35][CH:36]=1)=[O:31]

参加物

7

反応物 4

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 67001404(R)-tert-Butoxycarbonylamino-[4-((S)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-phenyl]-acetic acidHCID 866040402-((S)-2-amino-3-phenyl-propionylamino)-thiazole-4-carboxylic acid methyl ester

生成物 1

HCID 866040552-((S)-2-{(R)-2-tert-butoxycarbonylamino-2-[4-((S)-2,2-dimethyl-[1,3]dioxolan4-ylmethoxy)-phenyl]-acetylamino}-3-phenyl-propionylamino)-thiazole-4-carboxylic acid methyl ester収率 38.5%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

(R)-tert-Butoxycarbonylamino-[4-((S)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-phenyl]-acetic acid (280 mg, 0.73 mmol), 2-((S)-2-amino-3-phenyl-propionylamino)-thiazole-4-carboxylic acid methyl ester (203 mg, 0.66 mmol) (prepared as described in example 10, step 1), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (191 mg, 1.0 mmol) and 1-hydroxybenzotriazole hydrate (135 mg, 1.0 mmol) were combined in dichloromethane (5 mL) and stirred overnight at room temperature. The resulting solution was poured into ethyl acetate and washed with 0.2 M aqueous hydrochloric acid, water, brine and dried over magnesium sulfate. The solvents were removed and the crude was purified by chromatography over silica gel gradient eluted between 40% and 50% v/v ethyl acetate in hexane to give 2-((S)-2-{(R)-2-tert-butoxycarbonylamino-2-[4-((S)-2,2-dimethyl-[1,3]dioxolan4-ylmethoxy)-phenyl]-acetylamino}-3-phenyl-propionylamino)-thiazole-4-carboxylic acid methyl ester as a foam (170 mg, 38%).

後処理

  1. washwashed with 0.2 M aqueous hydrochloric acid, water, brine
  2. dry with materialdried over magnesium sulfate
  3. customThe solvents were removed
  4. customthe crude was purified by chromatography over silica gel gradient
  5. washeluted between 40% and 50% v/v ethyl acetate in hexane

出典と根拠

ORDレコード
ord-da667886cf9f40c89aa83b7ccf8d330c
出典データセット
uspto-grants-2008_05
特許番号
US07371869B2

反応ノート

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