Sodium Iodide → 4-O-tert-butyl 1-O-[(4-methoxyphenyl)methyl] (2S)-2-[(Z)-[2-[[(5R,6R,7R)-2-benzhydryloxycarbonyl-3-(iodomethyl)-5,8-dioxo-5lambda4-thia-1-azabicyclo[4.2.0]oct-2-en-7-yl]amino]-1-[5-chloro-2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-oxoethylidene]amino]oxybutanedioate

HRID 525914노트

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HRID 525914 반응식
[CH:1]([O:14][C:15]([C:17]1[N:18]2[C@H:21]([S@:22](=[O:27])[CH2:23][C:24]=1[CH2:25]Cl)[C@H:20]([NH:28][C:29](=[O:68])/[C:30](=[N:45]\[O:46][C@@H:47]([CH2:60][C:61]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62])[C:48]([O:50][CH2:51][C:52]1[CH:57]=[CH:56][C:55]([O:58][CH3:59])=[CH:54][CH:53]=1)=[O:49])/[C:31]1[N:32]=[C:33]([NH:37][C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[S:34][C:35]=1[Cl:36])[C:19]2=[O:69])=[O:16])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[I-:70].[Na+]>C(#N)C>[CH:1]([O:14][C:15]([C:17]1[N:18]2[C@H:21]([S@:22](=[O:27])[CH2:23][C:24]=1[CH2:25][I:70])[C@H:20]([NH:28][C:29](=[O:68])/[C:30](=[N:45]\[O:46][C@@H:47]([CH2:60][C:61]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62])[C:48]([O:50][CH2:51][C:52]1[CH:57]=[CH:56][C:55]([O:58][CH3:59])=[CH:54][CH:53]=1)=[O:49])/[C:31]1[N:32]=[C:33]([NH:37][C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[S:34][C:35]=1[Cl:36])[C:19]2=[O:69])=[O:16])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

참가 물질

4

반응물 2

HCID 5238Sodium IodideHCID 903733644-O-tert-butyl 1-O-[(4-methoxyphenyl)methyl] (2S)-2-[(Z)-[2-[[(5R,6R,7R)-2-benzhydryloxycarbonyl-3-(chloromethyl)-5,8-dioxo-5lambda4-thia-1-azabicyclo[4.2.0]oct-2-en-7-yl]amino]-1-[5-chloro-2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-oxoethylidene]amino]oxybutanedioate

생성물 1

HCID 903733704-O-tert-butyl 1-O-[(4-methoxyphenyl)methyl] (2S)-2-[(Z)-[2-[[(5R,6R,7R)-2-benzhydryloxycarbonyl-3-(iodomethyl)-5,8-dioxo-5lambda4-thia-1-azabicyclo[4.2.0]oct-2-en-7-yl]amino]-1-[5-chloro-2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-oxoethylidene]amino]oxybutanedioate수율 59.9%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

실험 절차

To a solution of (S)-4-tert-butyl 1-(4-methoxybenzyl) 2-(((Z)-(2-(((5R,6R,7R)-2-((benzhydryloxy)carbonyl)-3-(chloromethyl)-5-oxido-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-7-yl)amino)-1-(2-((tert-butoxycarbonyl)amino)-5-chlorothiazol-4-yl)-2-oxoethylidene)amino)oxy)succinate (27 g, 24.98 mmol) in Acetonitrile (300 mL) was added sodium iodide (5.62 g, 37.5 mmol). The mixture was stirred at room temperature over 1.5 h. LCMS indicated completion of the reaction. The solid was filtered off, the filtrate was concentrated under vacuum, and the residue was purified by CombiFlash Rf automated silica gel chromatography (330 g column), eluting with EtOAc/Hexanes (0-50%) to afford (S)-4-tert-butyl 1-(4-methoxybenzyl) 2-(((Z)-(2-(((5R,6R,7R)-2-((benzhydryloxy)carbonyl)-3-(iodomethyl)-5-oxido-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-7-yl)amino)-1-(2-((tert-butoxycarbonyl)amino)-5-chlorothiazol-4-yl)-2-oxoethylidene)amino)oxy)succinate (18 g, 14.97 mmol, 59.9% yield) as a red-brown solid. LCMS: (M+H)+: 1118.1

후처리

  1. customcompletion of the reaction
  2. filtrationThe solid was filtered off
  3. concentrationthe filtrate was concentrated under vacuum
  4. customthe residue was purified by CombiFlash Rf automated silica gel chromatography (330 g column)
  5. washeluting with EtOAc/Hexanes (0-50%)

출처 및 근거

ORD 기록
ord-ea04e896d0fb4e32bb7555ef89dc4d36
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09340556B2

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