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 513365Notes

Reaction equation

HRID 513365 reaction equation
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]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 86717768HCID 86717768, compoundHCID 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

Product 1

HCID 86717771prop-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-carboxylateYield 35%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
75 °C

Procedure

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]+.

Workup

  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)

Sources & evidence

ORD record
ord-760be87df7314406976ddc5764fd7fad
Source dataset
uspto-grants-2015_08
Patent number
US09102704B2

Reaction notes

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