Diisopropylethylamine → (S)-5-bromo-6-(3-(hydroxymethyl)pyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

HRID 525662

Reaktionsgleichung

Reaktionsgleichung von HRID 525662
[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].C1CNC([CH2:28][OH:29])C1.Cl.CC[N:33]([CH:37]([CH3:39])C)[CH:34]([CH3:36])C>CC(O)C>[Br:1][C:2]1[C:3]([N:33]2[CH2:34][CH2:36][C@H:39]([CH2:28][OH:29])[CH2:37]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

5

Edukt 3

HCID 81531DiisopropylethylamineHCID 17802800Pyrrolidin-2-ylmethanol hydrochlorideHCID 867025955-bromo-6-chloro-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Produkt 1

HCID 86702601(S)-5-bromo-6-(3-(hydroxymethyl)pyrrolidin-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), (S)-beta-prolinol hydrochloride (226 mg, 1.643 mmol), DIPEA (662 μL, 3.79 mmol) and iPrOH (1.945 mL) were added to a MW vial and subjected to MW irradiation at 140° C. for 60 min. The solvent was evaporated off under reduced pressure and the residue was treated with aq. 0.5 M HCl (20 mL) and extracted with EtOAc. The combined extracts were washed with 0.5 M HCl (10 mL) and water, dried over MgSO4 and the solvent was evaporated off under reduced pressure to give the product which was triturated with cyclohexane, filtered and dried to afford the title compound as a white solid. UPLC-MS (Condition 1) tR=2.76 min, m/z=460.0/462.0 [M+H]+, m/z=458.0/460.0 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.59-1.76 (m, 1H) 1.92-2.04 (m, 1H) 2.26-2.44 (m, 1H) 3.37-3.50 (m, 2H) 3.56 (dd, J=11.00, 7.34 Hz, 1H) 3.67-3.85 (m, 3H) 4.71 (br. s, 1H) 7.35 (d, J=8.56 Hz, 2H) 7.85 (d, 1H) 8.34 (d, J=1.96 Hz, 1H) 8.68 (d, J=1.96 Hz, 1H) 10.21 (s, 1H).

Aufarbeitung

  1. customsubjected to MW irradiation at 140° C. for 60 min
  2. customThe solvent was evaporated off under reduced pressure
  3. additionthe residue was treated with aq. 0.5 M HCl (20 mL)
  4. extractionextracted with EtOAc
  5. washThe combined extracts were washed with 0.5 M HCl (10 mL) and water
  6. dry with materialdried over MgSO4
  7. customthe solvent was evaporated off under reduced pressure
  8. customto give the product which
  9. customwas triturated with cyclohexane
  10. filtrationfiltered
  11. customdried

Quellen und Nachweise

ORD-Eintrag
ord-6d32ff921c9e4adebc383f029299022e
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09340537B2

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