Sirolimus → Everolimus

HRID 1524849Notes

Reaction equation

HRID 1524849 reaction equation
[O:1]([CH2:9][CH2:10]O[Si](C(C)(C)C)(C)C)S(C(F)(F)F)(=O)=O.[CH3:19][C@H:20]1[C@@:59]2([OH:61])[O:60][C@H:23]([CH2:24][C@H:25]([O:82][CH3:83])[C:26]([CH3:81])=[CH:27][CH:28]=[CH:29][CH:30]=[CH:31][C@@H:32]([CH3:80])[CH2:33][C@@H:34]([CH3:79])[C:35]([C@H:37]([O:77][CH3:78])[C@H:38]([OH:76])[C:39]([CH3:75])=[CH:40][C@@H:41]([CH3:74])[C:42]([CH2:44][C@@H:45]([C@@H:62]([CH2:64][C@H:65]3[CH2:70][C@@H:69]([O:71][CH3:72])[C@H:68]([OH:73])[CH2:67][CH2:66]3)[CH3:63])[O:46][C:47]([C@H:49]3[N:54]([C:55]([C:57]2=[O:58])=[O:56])[CH2:53][CH2:52][CH2:51][CH2:50]3)=[O:48])=[O:43])=[O:36])[CH2:22][CH2:21]1>>[CH3:19][C@H:20]1[C@@:59]2([OH:61])[O:60][C@H:23]([CH2:24][C@H:25]([O:82][CH3:83])[C:26]([CH3:81])=[CH:27][CH:28]=[CH:29][CH:30]=[CH:31][C@@H:32]([CH3:80])[CH2:33][C@@H:34]([CH3:79])[C:35]([C@H:37]([O:77][CH3:78])[C@H:38]([OH:76])[C:39]([CH3:75])=[CH:40][C@@H:41]([CH3:74])[C:42]([CH2:44][C@@H:45]([C@@H:62]([CH2:64][C@H:65]3[CH2:70][C@@H:69]([O:71][CH3:72])[C@H:68]([O:73][CH2:10][CH2:9][OH:1])[CH2:67][CH2:66]3)[CH3:63])[O:46][C:47]([C@H:49]3[N:54]([C:55]([C:57]2=[O:58])=[O:56])[CH2:53][CH2:52][CH2:51][CH2:50]3)=[O:48])=[O:43])=[O:36])[CH2:22][CH2:21]1

Participants

3

Reactant 2

HCID 5284616SirolimusHCID 156781072-((tert-Butyldimethylsilyl)oxy)ethyl trifluoromethanesulfonate

Product 1

HCID 6442177Everolimus

Procedure

Accordingly, the present disclosure relates to a process for obtaining Everolimus, said process comprising acts of a) adding 2-(-t-butyldimethylsilyl)oxyethyl triflate (2) to Sirolimus to obtain crude 40-O-[2-(t-butyldimethylsilyl)oxy]ethyl rapamycin (3) and b) treating and purifying the crude 40-O-[2-(t-butyldimethylsilyl)oxy]ethyl rapamycin (3) to obtain Everolimus; a process for obtaining Everolimus, said process comprising acts of a) adding Sirolimus to 2-(-t-butyldimethylsilyl)oxyethyl triflate (2) to obtain crude 40-O-[2-(t-butyldimethylsilyl)oxy]ethyl rapamycin (3) and b) treating and purifying the crude 40-O-[2-(t-butyldimethylsilyl)oxy]ethyl rapamycin (3) to obtain Everolimus; a process for obtaining Everolimus, said process comprising acts of a) obtaining a mixture comprising Sirolimus, 2-(t-butyldimethylsilyl)ethylene glycol (1), base and organic solvent, in any order thereof, b) adding 2-(-t-butyldimethylsilyl)oxyethyl triflate (2) to the mixture to obtain crude 40-O-[2-(t-butyldimethylsilyl)oxy]ethyl rapamycin (3) and c) treating and purifying the crude 40-O-[2-(t-butyldimethylsilyl)oxy]ethyl rapamycin (3) to obtain Everolimus; and a process for obtaining Everolimus, said process comprising acts of a) obtaining a mixture comprising 2-(-t-butyldimethylsilyl)oxyethyl triflate (2), 2-(t-butyldimethylsilyl)ethylene glycol (1), base and organic solvent, in any order thereof, b) adding Sirolimus to the mixture to obtain crude 40-O-[2-(t-butyldimethylsilyl)oxy]ethyl rapamycin (3) and c) treating and purifying the crude 40-O-[2-(t-butyldimethylsilyl)oxy]ethyl rapamycin (3) to obtain Everolimus.

Workup

  1. customto obtain crude 40-O-[2-(t-butyldimethylsilyl)oxy]ethyl rapamycin (3) and b)
  2. additiontreating
  3. custompurifying the crude 40-O-[2-(t-butyldimethylsilyl)oxy]ethyl rapamycin (3)

Sources & evidence

ORD record
ord-602ff235a03b4266ad2be31a49442af8
Source dataset
uspto-grants-2015_07
Patent number
US09079921B2

Reaction notes

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