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 2222978노트

반응식

HRID 2222978 반응식
[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]

참가 물질

7

반응물 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

생성물 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 ester수율 38.5%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매

실험 절차

(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%).

후처리

  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

출처 및 근거

ORD 기록
ord-da667886cf9f40c89aa83b7ccf8d330c
출처 데이터셋
uspto-grants-2008_05
특허 번호
US07371869B2

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