Hydrochloric Acid → HCID 178432513, Verbindung

HRID 1812372

Reaktionsgleichung

Reaktionsgleichung von HRID 1812372
[Cl:1][C:2]1[C:7]([NH:8][S:9]([CH3:12])(=[O:11])=[O:10])=[CH:6][C:5]([NH:13][C:14]2[C:19]([C:20]3[N:28]=[C:27]([CH3:29])[N:26]=[C:25]4[C:21]=3[N:22]=[CH:23][N:24]4C3CCCCO3)=[CH:18][C:17]([CH:36]([N:38]3[CH2:43][CH2:42][O:41][CH2:40][CH2:39]3)[CH3:37])=[CH:16][N:15]=2)=[CH:4][N:3]=1.Cl.C(O)(=O)CC(CC(O)=O)(C(O)=O)O.[OH-].[Na+]>[OH-].[Na+].C1COCC1>[Cl:1][C:2]1[C:7]([NH:8][S:9]([CH3:12])(=[O:11])=[O:10])=[CH:6][C:5]([NH:13][C:14]2[C:19]([C:20]3[N:28]=[C:27]([CH3:29])[N:26]=[C:25]4[C:21]=3[N:22]=[CH:23][NH:24]4)=[CH:18][C:17]([CH:36]([N:38]3[CH2:39][CH2:40][O:41][CH2:42][CH2:43]3)[CH3:37])=[CH:16][N:15]=2)=[CH:4][N:3]=1

Komponenten

6

Edukt 3

HCID 313Hydrochloric AcidHCID 23674961citric acid NaOHHCID 86647079N-(2-chloro-5-(3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)-5-(1-morpholinoethyl)pyridin-2-ylamino)pyridin-3-yl)methanesulfonamide

Produkt 1

HCID 178432513HCID 178432513, VerbindungAusbeute 70,6 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 14798Sodium HydroxideKatalysatorHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a 20 mL scintillation vial, N-(2-chloro-5-(3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)-5-(1-morpholinoethyl)pyridin-2-ylamino)pyridin-3-yl)methanesulfonamide (0.165 g, 0.263 mmol) and 5 N hydrochloric acid (0.5 mL, 2.5 mmol) were mixed into THF (3 mL). The solution was stirred at room temperature for 30 min. 10 mL of buffer (pH 5, citric acid/NaOH) was added and the pH was further adjusted to about 5 by adding a few drops of 6 N NaOH. The aqueous phase was extracted with 10% isopropanol in chloroform (3×20 mL). The combined organic phases were dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by preparative HPLC using a Phenomenex, Gemni 5 micron C18 100×30 mm column (1% to 90% CH3CN w/0.1% TFA/H2O w/0.1% TFA in 10 min). The corresponding fractions were collected and concentrated down to dryness. The residue was treated with about 5 mL of pH 5 buffer and pH 7 buffer were added to adjust pH to about 6. The aqueous phase was extracted with 10% isopropanol in chloroform (3×20 mL). The combined organic phases were dried over sodium sulfate, filtered and concentrated in vacuo to afford 0.101 g of yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 13.65 (br. s., 1H) 13.11 (br. s., 1H) 9.82 (br. s., 1H) 9.68 (br. s., 1H) 8.71 (d, J=1.96 Hz, 1H) 8.66 (s, 1H) 8.53 (s, 1H) 8.34 (d, J=1.17 Hz, 1H) 3.50-3.67 (m, 5H) 3.15 (s, 3H) 2.88 (s, 3H) 2.35-2.46 (m, 2H) 1.42 (d, J=6.65 Hz, 3H). Note: 2 protons were buried under DMSO peak and could not be integrated. m/z (ESI, positive ion): 544.0 (M+H)+.

Aufarbeitung

  1. extractionThe aqueous phase was extracted with 10% isopropanol in chloroform (3×20 mL)
  2. dry with materialThe combined organic phases were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by preparative HPLC
  6. customC18 100×30 mm column (1% to 90% CH3CN w/0.1% TFA/H2O w/0.1% TFA in 10 min)
  7. customThe corresponding fractions were collected
  8. concentrationconcentrated down to dryness
  9. additionThe residue was treated with about 5 mL of pH 5 buffer
  10. additionpH 7 buffer were added
  11. extractionThe aqueous phase was extracted with 10% isopropanol in chloroform (3×20 mL)
  12. dry with materialThe combined organic phases were dried over sodium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-9463d3cf22a34997bbb6d517f4403237
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08362241B2

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