Hydrochloric Acid → (2S)-2-(3-(2-chlorophenyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yloxy)-N-(5-chloropyridin-2-yl)-3-(2-hydroxyethoxy)propanamide

HRID 1098042Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1098042
Cl.[Si]([O:19][CH2:20][CH2:21][O:22][CH2:23][C@H:24]([O:35][C:36]1[C:37]2[N:44]=[N:43][N:42]([C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][C:46]=3[Cl:51])[C:38]=2[N:39]=[CH:40][N:41]=1)[C:25]([NH:27][C:28]1[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][N:29]=1)=[O:26])(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1>CO>[Cl:51][C:46]1[CH:47]=[CH:48][CH:49]=[CH:50][C:45]=1[N:42]1[C:38]2[N:39]=[CH:40][N:41]=[C:36]([O:35][C@@H:24]([CH2:23][O:22][CH2:21][CH2:20][OH:19])[C:25]([NH:27][C:28]3[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][N:29]=3)=[O:26])[C:37]=2[N:44]=[N:43]1

Komponenten

4

Edukt 2

HCID 313Hydrochloric AcidHCID 57504543(2S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-(3-(2-chlorophenyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yloxy)-N-(5-chloropyridin-2-yl)propanamide

Produkt 1

HCID 57504544(2S)-2-(3-(2-chlorophenyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yloxy)-N-(5-chloropyridin-2-yl)-3-(2-hydroxyethoxy)propanamideAusbeute 31,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Versuchsvorschrift

Hydrochloric acid (10%, 1 mL) was added dropwise to (2S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-(3-(2-chlorophenyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yloxy)-N-(5-chloropyridin-2-yl)propanamide (Intermediate AP4) (180 mg, 0.25 mmol) in methanol (20.00 mL) at room temperature. The resulting solution was stirred for 4 hours. Most of the methanol was evaporated and the remaining aq. soln was diluted with saturated NH4Cl and extracted with EtOAc (2×30 mL). The organic layers were combined, dried (MgSO4) and evaporated to give crude product. The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 50 mm diameter, 150 mm length), using decreasingly polar mixtures of water (containing 0.1% formic acid) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford (2S)-2-(3-(2-chlorophenyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yloxy)-N-(5-chloropyridin-2-yl)-3-(2-hydroxyethoxy)propanamide (38.0 mg, 31.4%). 1H NMR (400 MHz, CDCl3) δ3.72-3.83 (m, 4H), 4.19-4.32 (m, 2H), 6.15 (t, 1H), 7.50-7.63 (m, 3H), 7.66-7.72 (m, 2H), 8.15-8.27 (m, 2H), 8.72 (s, 1H), 9.16 (s, 1H) OH not observed; m/z (ESI+) (M+H)+=490.16; HPLC tR=2.15 min

Aufarbeitung

  1. customMost of the methanol was evaporated
  2. additionthe remaining aq. soln was diluted with saturated NH4Cl
  3. extractionextracted with EtOAc (2×30 mL)
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. customto give crude product
  7. customThe crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 50 mm diameter, 150 mm length)
  8. additionFractions containing the desired compound
  9. customwere evaporated to dryness

Quellen und Nachweise

ORD-Eintrag
ord-46071383d5b043aa88ac12a7224ecf83
Quelldatensatz
uspto-grants-2012_03
Patentnummer
US08143263B2

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