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Potassium Carbonate → prop-2-enyl (6S,6aS)-3-[3-[[(6S,6aS)-6-[tert-butyl(dimethyl)silyl]oxy-2-methoxy-5-[[4-[[(2R)-2-[[(2R)-3-methyl-2-(prop-2-enoxycarbonylamino)butanoyl]amino]propanoyl]amino]phenyl]methoxycarbonyl]-11-oxo-8-[(E)-prop-1-enyl]-6a,7-dihydro-6H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl]oxy]propoxy]-6-[tert-butyl(dimethyl)silyl]oxy-2-methoxy-11-oxo-8-[(E)-prop-1-enyl]-6a,7-dihydro-6H-pyrrolo[2,1-c][1,4]benzodiazepine-5-carboxylate

HRID 513365
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HRID 513365 반응식
C(=O)([O-])[O-].[K+].[K+].[Si:7]([O:14][C@@H:15]1[N:21]([C:22]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][C:29]([NH:32][C:33](=[O:50])[C@@H:34]([NH:36][C:37](=[O:49])[C@@H:38]([NH:42][C:43]([O:45][CH2:46][CH:47]=[CH2:48])=[O:44])[CH:39]([CH3:41])[CH3:40])[CH3:35])=[CH:28][CH:27]=2)=[O:23])[C:20]2[CH:51]=[C:52]([OH:57])[C:53]([O:55][CH3:56])=[CH:54][C:19]=2[C:18](=[O:58])[N:17]2[CH:59]=[C:60](/[CH:62]=[CH:63]/[CH3:64])[CH2:61][C@@H:16]12)([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8].[Si:65]([O:72][C@@H:73]1[N:79]([C:80]([O:82][CH2:83][CH:84]=[CH2:85])=[O:81])[C:78]2[CH:86]=[C:87]([O:92][CH2:93][CH2:94][CH2:95]I)[C:88]([O:90][CH3:91])=[CH:89][C:77]=2[C:76](=[O:97])[N:75]2[CH:98]=[C:99](/[CH:101]=[CH:102]/[CH3:103])[CH2:100][C@@H:74]12)([C:68]([CH3:71])([CH3:70])[CH3:69])([CH3:67])[CH3:66]>CC(C)=O>[CH2:46]([O:45][C:43]([NH:42][C@H:38]([CH:39]([CH3:41])[CH3:40])[C:37]([NH:36][C@H:34]([CH3:35])[C:33]([NH:32][C:29]1[CH:28]=[CH:27][C:26]([CH2:25][O:24][C:22]([N:21]2[C:20]3[CH:51]=[C:52]([O:57][CH2:95][CH2:94][CH2:93][O:92][C:87]4[C:88]([O:90][CH3:91])=[CH:89][C:77]5[C:76](=[O:97])[N:75]6[CH:98]=[C:99](/[CH:101]=[CH:102]/[CH3:103])[CH2:100][C@H:74]6[C@H:73]([O:72][Si:65]([C:68]([CH3:71])([CH3:69])[CH3:70])([CH3:67])[CH3:66])[N:79]([C:80]([O:82][CH2:83][CH:84]=[CH2:85])=[O:81])[C:78]=5[CH:86]=4)[C:53]([O:55][CH3:56])=[CH:54][C:19]=3[C:18](=[O:58])[N:17]3[CH:59]=[C:60](/[CH:62]=[CH:63]/[CH3:64])[CH2:61][C@H:16]3[C@@H:15]2[O:14][Si:7]([C:10]([CH3:11])([CH3:12])[CH3:13])([CH3:8])[CH3:9])=[O:23])=[CH:31][CH:30]=1)=[O:50])=[O:49])=[O:44])[CH:47]=[CH2:48]
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참가 물질

5

반응물 3

HCID 11430Potassium CarbonateHCID 86717768HCID 86717768, 화합물HCID 86717769(11 S,11aS)-4-((S)-2-((S)-2-(allyloxycarbonylamino)-3-methylbutanamido)propanamido)benzyl 11-(tert-butyldimethylsilyloxy)-8-hydroxy-7-methoxy-5-oxo-2-((E)-prop-1-enyl)-11,11a-dihydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-10(5H)-carboxylate

생성물 1

HCID 86717771
prop-2-enyl (6S,6aS)-3-[3-[[(6S,6aS)-6-[tert-butyl(dimethyl)silyl]oxy-2-methoxy-5-[[4-[[(2R)-2-[[(2R)-3-methyl-2-(prop-2-enoxycarbonylamino)butanoyl]amino]propanoyl]amino]phenyl]methoxycarbonyl]-11-oxo-8-[(E)-prop-1-enyl]-6a,7-dihydro-6H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl]oxy]propoxy]-6-[tert-butyl(dimethyl)silyl]oxy-2-methoxy-11-oxo-8-[(E)-prop-1-enyl]-6a,7-dihydro-6H-pyrrolo[2,1-c][1,4]benzodiazepine-5-carboxylate
수율 35%

시약·촉매·용매 1

HCID 180Acetone용매

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온도
75 °C

실험 절차

Potassium carbonate (0.030 g, 0.21 mmol, 1.0 eq) was added to a solution of the phenol 18 (0.175 g, 0.21 mmol, 1.0 eq) and the iodo linker 49 (0.214 g, 0.32 mmol, 1.5 eq) in acetone (10 mL). The reaction mixture was heated under a nitrogen atmosphere at 75° C. in a sealed flask for 17 hours. The reaction mixture was concentrated to dryness under reduced pressure and purified by flash chromatography (silica gel, 2/98 v/v methanol/DCM to 5/95 v/v methanol/DCM) to afford the product as a pale yellow solid (0.100 g, 35%). LC/MS (4.293 min (ES+)), m/z: 1359.13 [M]+.

후처리

  1. concentrationThe reaction mixture was concentrated to dryness under reduced pressure
  2. custompurified by flash chromatography (silica gel, 2/98 v/v methanol/DCM to 5/95 v/v methanol/DCM)

출처 및 근거

ORD 기록
ord-760be87df7314406976ddc5764fd7fad
출처 데이터셋
uspto-grants-2015_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09102704B2

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