Itraconazole → Malic Acid

HRID 2076717

Reaktionsgleichung

Reaktionsgleichung von HRID 2076717
[C:1]([OH:9])(=[O:8])[C@H:2]([CH2:4][C:5]([OH:7])=[O:6])[OH:3].[CH3:10][CH2:11][CH:12]([N:14]1[N:19]=[CH:18][N:17]([C:20]2[CH:25]=[CH:24][C:23]([N:26]3[CH2:31][CH2:30][N:29]([C:32]4[CH:37]=[CH:36][C:35]([O:38][CH2:39][C@@H:40]5[O:44][C@:43]([C:51]6[CH:56]=[CH:55][C:54]([Cl:57])=[CH:53][C:52]=6[Cl:58])([CH2:45][N:46]6[N:50]=[CH:49][N:48]=[CH:47]6)[O:42][CH2:41]5)=[CH:34][CH:33]=4)[CH2:28][CH2:27]3)=[CH:22][CH:21]=2)[C:15]1=[O:16])[CH3:13].CCC(N1N=CN(C2C=CC(N3CCN(C4C=CC(OC[C@@H]5O[C@](C6C=CC(Cl)=CC=6Cl)(CN6N=CN=C6)OC5)=CC=4)CC3)=CC=2)C1=O)C.[C:108]([OH:117])(=[O:116])[C@@H:109]([C@H:111]([C:113]([OH:115])=[O:114])[OH:112])O>C1COCC1>[CH3:10][CH2:11][CH:12]([N:14]1[N:19]=[CH:18][N:17]([C:20]2[CH:25]=[CH:24][C:23]([N:26]3[CH2:31][CH2:30][N:29]([C:32]4[CH:37]=[CH:36][C:35]([O:38][CH2:39][C@@H:40]5[O:44][C@:43]([C:51]6[CH:56]=[CH:55][C:54]([Cl:57])=[CH:53][C:52]=6[Cl:58])([CH2:45][N:46]6[N:50]=[CH:49][N:48]=[CH:47]6)[O:42][CH2:41]5)=[CH:34][CH:33]=4)[CH2:28][CH2:27]3)=[CH:22][CH:21]=2)[C:15]1=[O:16])[CH3:13].[C:1]([OH:9])(=[O:8])[CH:2]([CH2:4][C:5]([OH:7])=[O:6])[OH:3].[CH2:109]([C:108]([OH:117])=[O:116])[C@H:111]([OH:112])[C:113]([OH:115])=[O:114]

Komponenten

7

Edukt 3

HCID 55283Itraconazole3×HCID 222656L-Malic Acid2×HCID 131728781cis-itraconazole L-tartaric acid

Produkt 3

HCID 525Malic AcidHCID 55283ItraconazoleHCID 222656L-Malic Acid

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

Co-crystals of itraconazole and malic acid were prepared. To prepare the L-malic acid co-crystal salt of cis-itraconazole, 100.4 mg of cis-itraconazole free base, 0.50 mL of THF, and a magnetic stir bar were charged into a screw cap vial. A solution of 191.3 mg of L(−)malic acid in 5.0 mL of THF was prepared. 0.50 mL of the L-malic acid solution was added to the vial containing cis-itraconazole and the solution was heated with a heat gun to dissolve. The solution was allowed to cool and was then seeded with <1 mg of the salt from cis-itraconazole-L-tartaric acid co-crystal. The cooled crystals were filtered in a centrifuge filter tube. The filter cake was broken-up and allowed to air-dry prior to analysis. (See FIGS. 18 and 19)

Aufarbeitung

  1. additionwere charged into a screw
  2. customcap vial
  3. temperaturethe solution was heated with a heat gun
  4. dissolutionto dissolve
  5. temperatureto cool
  6. filtrationThe cooled crystals were filtered in a centrifuge
  7. filtrationfilter tube
  8. customto air-dry

Quellen und Nachweise

ORD-Eintrag
ord-6fc3c7a2d0c14917a244ca35d1dc3421
Quelldatensatz
uspto-grants-2011_04
Patentnummer
US07927613B2

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