Hydrochloric Acid → 5-bromo-6-((3S,4S)-3,4-dihydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

HRID 525690

Reaktionsgleichung

Reaktionsgleichung von HRID 525690
[Br:1][C:2]1[C:3](Cl)=[N:4][CH:5]=[C:6]([CH:21]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=1)=[O:8].[NH:23]1[CH2:27][C@H:26]([OH:28])[C@@H:25]([OH:29])[CH2:24]1.CCN(C(C)C)C(C)C.Cl>CC(O)C>[Br:1][C:2]1[C:3]([N:23]2[CH2:27][C@H:26]([OH:28])[C@@H:25]([OH:29])[CH2:24]2)=[N:4][CH:5]=[C:6]([CH:21]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=1)=[O:8]

Komponenten

6

Edukt 4

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 1461981,4-Dideoxy-1,4-iminothreitolHCID 867025955-bromo-6-chloro-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Produkt 1

HCID 899079005-bromo-6-((3S,4S)-3,4-dihydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 3776IsopropanolLösungsmittel

Versuchsvorschrift

5-Bromo-6-chloro-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 6.2, 500 mg, 1.264 mmol, (3S,4S)-pyrrolidine-3,4-diol (157 mg, 1.517 mmol), DIPEA (442 μL, 2.53 mmol) and iPrOH (1.264 mL) were added to a MW vial, which was sealed and subjected to MW irradiation at 140° C. for 30 min. The solvent was evaporated off under reduced pressure to give a residue which was treated with 0.5 M HCl (10 mL) and extracted with EtOAc. The combined extracts were washed with HCl 0.5 M and brine, diluted with MeOH (20 mL), dried over MgSO4 and the solvent was evaporated off under reduced pressure and the product was crystallized from EtOAc/MeOH afforded the title compound as a white solid. UPLC-MS (Condition 1) tR=2.48 min, m/z=462.0/464.0 [M+H]+, m/z=460.0/462.0 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 3.56 (d, J=11.25 Hz, 2H) 3.94-4.06 (m, 4H) 4.79 (br. s, 2H) 7.34 (d, J=8.80 Hz, 2H) 7.88 (d, J=9.05 Hz, 2H) 8.38 (d, J=1.96 Hz, 1H) 8.71 (d, J=1.96 Hz, 1H) 10.34 (s, 1H).

Aufarbeitung

  1. customwas sealed
  2. customsubjected to MW irradiation at 140° C. for 30 min
  3. customThe solvent was evaporated off under reduced pressure
  4. customto give a residue which
  5. extractionextracted with EtOAc
  6. washThe combined extracts were washed with HCl 0.5 M and brine
  7. additiondiluted with MeOH (20 mL)
  8. dry with materialdried over MgSO4
  9. customthe solvent was evaporated off under reduced pressure
  10. customthe product was crystallized from EtOAc/MeOH

Quellen und Nachweise

ORD-Eintrag
ord-35177b1bab2c42e89b9e918fd39d616f
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09340537B2

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