HCID 178496632, Verbindung → Sirolimus

HRID 1437794Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1437794
[CH3:1][C@H:2]1[C@@:41]2([OH:43])[O:42][C@H:5]([CH2:6][C@H:7]([O:72][CH3:73])[C:8]([CH3:71])=[CH:9][CH:10]=[CH:11][CH:12]=[CH:13][C@@H:14]([CH3:70])[CH2:15][C@@H:16]([CH3:69])[C:17]([C@H:19]([O:67][CH3:68])[C@H:20]([OH:66])[C:21]([CH3:65])=[CH:22][C@@H:23]([CH3:64])[C:24]([CH2:26][C@@H:27]([C@@H:44]([CH2:46][C@H:47]3[CH2:52][C@@H:51]([O:53][CH3:54])[C@H:50]([O:55][C:56]([C:58]([CH2:62][OH:63])([CH2:60][OH:61])[CH3:59])=[O:57])[CH2:49][CH2:48]3)[CH3:45])[O:28][C:29]([C@H:31]3[N:36]([C:37]([C:39]2=[O:40])=[O:38])[CH2:35][CH2:34][CH2:33][CH2:32]3)=[O:30])=[O:25])=[O:18])[CH2:4][CH2:3]1.[BH:74]([O-:76])[O-:75]>CC(C)=O>[CH3:1][C@H:2]1[C@@:41]2([OH:43])[O:42][C@H:5]([CH2:6][C@H:7]([O:72][CH3:73])[C:8]([CH3:71])=[CH:9][CH:10]=[CH:11][CH:12]=[CH:13][C@@H:14]([CH3:70])[CH2:15][C@@H:16]([CH3:69])[C:17]([C@H:19]([O:67][CH3:68])[C@H:20]([OH:66])[C:21]([CH3:65])=[CH:22][C@@H:23]([CH3:64])[C:24]([CH2:26][C@@H:27]([C@@H:44]([CH2:46][C@H:47]3[CH2:52][C@@H:51]([O:53][CH3:54])[C@H:50]([O:55][C:56]([C:58]([CH2:60][OH:61])([CH2:62][OH:63])[CH3:59])=[O:57])[CH2:49][CH2:48]3)[CH3:45])[O:28][C:29]([C@H:31]3[N:36]([C:37]([C:39]2=[O:40])=[O:38])[CH2:35][CH2:34][CH2:33][CH2:32]3)=[O:30])=[O:25])=[O:18])[CH2:4][CH2:3]1.[BH:74]([O-:76])[O-:75].[CH3:1][C@H:2]1[C@@:41]2([OH:43])[O:42][C@H:5]([CH2:6][C@H:7]([O:72][CH3:73])[C:8]([CH3:71])=[CH:9][CH:10]=[CH:11][CH:12]=[CH:13][C@@H:14]([CH3:70])[CH2:15][C@@H:16]([CH3:69])[C:17]([C@H:19]([O:67][CH3:68])[C@H:20]([OH:66])[C:21]([CH3:65])=[CH:22][C@@H:23]([CH3:64])[C:24]([CH2:26][C@@H:27]([C@@H:44]([CH2:46][C@H:47]3[CH2:52][C@@H:51]([O:53][CH3:54])[C@H:50]([OH:55])[CH2:49][CH2:48]3)[CH3:45])[O:28][C:29]([C@H:31]3[N:36]([C:37]([C:39]2=[O:40])=[O:38])[CH2:35][CH2:34][CH2:33][CH2:32]3)=[O:30])=[O:25])=[O:18])[CH2:4][CH2:3]1

Komponenten

4

Edukt 1

HCID 178496632HCID 178496632, Verbindung

Produkt 2

HCID 5284616SirolimusHCID 178496632HCID 178496632, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 180AcetoneLösungsmittel

Reaktionsbedingungen

Temperatur
58 °C

Versuchsvorschrift

Crude CCI-779 boronate (300 g) and acetone (900 g) was charged into a flask. The mixture was heated to reflux (55 to 61° C.) and held for 1 h. The mixture was cooled to 20-25° C. over 2-3 h, then distilled to remove acetone under vacuum (23-26″ Hg) at a pot temperature not exceeding 10-18° C. (final volume 940-960 mL). The diethyl ether (450 g) was added, stirred at 18-25° C. for 18 hours, and then filtered to give crude CCI-779 boronate (225 g, LOD=0.95%). The filtered crude CCI-779 boronate (224 g) and acetone (676 g) was charged into a flask. The mixture was heated to reflux (55 to 61° C.) and held for 1 h. The mixture was cooled to 19-25° C. over 2-3 h, then distilled to remove acetone under vacuum (18-20″ Hg) at a pot temperature of 18-20° C. (final volume 620 mL). The diethyl ether (338 g) was added, stirred at 18-25° C. for 18 hours, and then filtered. After washing 3 times using ether (250 mL each) to give CCI-779 boronate in 63% yield (LOD=0.57%, strength=85.9%, total impurities=1.8%, LSI=0.50, rapamycin=0.95%).

Aufarbeitung

  1. temperatureThe mixture was heated
  2. temperatureThe mixture was cooled to 20-25° C. over 2-3 h
  3. distillationdistilled
  4. customto remove acetone under vacuum (23-26″ Hg) at a pot temperature not
  5. customexceeding 10-18° C.
  6. additionThe diethyl ether (450 g) was added
  7. filtrationfiltered
  8. customto give crude CCI-779 boronate (225 g, LOD=0.95%)
  9. filtrationThe filtered crude CCI-779 boronate (224 g) and acetone (676 g)
  10. additionwas charged into a flask
  11. temperatureThe mixture was heated
  12. temperatureto reflux (55 to 61° C.)
  13. waitheld for 1 h
  14. temperatureThe mixture was cooled to 19-25° C. over 2-3 h
  15. distillationdistilled
  16. customto remove acetone under vacuum (18-20″ Hg) at a pot temperature of 18-20° C. (final volume 620 mL)
  17. additionThe diethyl ether (338 g) was added
  18. stirringstirred at 18-25° C. for 18 hours
  19. filtrationfiltered
  20. washAfter washing 3 times

Quellen und Nachweise

ORD-Eintrag
ord-ba79a2bb92424b24a70eb47b294dc359
Quelldatensatz
uspto-grants-2009_11
Patentnummer
US07622578B2

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