Diisopropylethylamine → HCID 178429372, Verbindung

HRID 707366Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 707366
FC(F)(F)S(O[C:7]1[CH:16]=[CH:15][C:14]2[C:9](=[CH:10][CH:11]=[CH:12][N:13]=2)[N:8]=1)(=O)=O.Cl.[NH2:20][C@H:21]1[CH2:24][C@H:23]([N:25]2[C:29]3[N:30]=[CH:31][N:32]=[CH:33][C:28]=3[C:27]([CH3:35])([CH3:34])[C:26]2=[O:36])[CH2:22]1.C(N(CC)C(C)C)(C)C>CS(C)=O.O>[N:8]1[C:9]2[C:14](=[N:13][CH:12]=[CH:11][CH:10]=2)[CH:15]=[CH:16][C:7]=1[NH:20][C@H:21]1[CH2:24][C@H:23]([N:25]2[C:29]3[N:30]=[CH:31][N:32]=[CH:33][C:28]=3[C:27]([CH3:34])([CH3:35])[C:26]2=[O:36])[CH2:22]1

Komponenten

6

Edukt 3

HCID 81531DiisopropylethylamineHCID 866942231,5-Naphthyridin-2-yl trifluoromethanesulfonateHCID 178429370HCID 178429370, Verbindung

Produkt 1

HCID 178429372HCID 178429372, VerbindungAusbeute 71,6 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 679Dimethyl SulfoxideLösungsmittelHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To suspension of 1,5-naphthyridin-2(1H)-one (0.200 g, 1.368 mmol) in Pyridine (1 mL) was added slowly trifluoromethanesulfonic anhydride (0.050 mL, 0.298 mmol). After the addition, the reaction mixture was stirred at room temperature for 18 h. The solvent was evaporated under high vacuum and residue diluted with water and extracted with EtOAc. EtOAc was washed with water, brine, dried over Na2SO4 and concentrated to give crude 1,5-naphthyridin-2-yl trifluoromethanesulfonate. To this crude 1,5-naphthyridin-2-yl trifluoromethanesulfonate (100 mg) in DMSO (0.5 mL) was added 7-(trans-3-aminocyclobutyl)-5,5-dimethyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one hydrochloride, INTERMEDIATE 62, (0.05 g, 0.186 mmol) and N,N-diisopropylethylamine (0.032 mL, 0.186 mmol). The mixture was heated to 100° C. for 2 hours, diluted with water and extracted with EtOAc. EtOAc was concentrated and residue purified with ISCO using silical gel column eluting with 0-100% EtOAc/hexanes to give the title compound 7-(trans-3-((1,5-naphthyridin-2-yl)amino)cyclobutyl)-5,5-dimethyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one (0.048 g, 0.133 mmol, 71.6% yield). m/z: 361.2; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.85 (s, 1 H) 8.62 (dd, J=4.21, 1.27 Hz, 1 H) 8.33 (s, 1 H) 8.07 (d, J=9.00 Hz, 1 H) 7.98 (d, J=8.22 Hz, 1 H) 7.45 (dd, J=8.51, 4.21 Hz, 1 H) 6.88 (d, J=9.00 Hz, 1 H) 5.46 (d, J=4.50 Hz, 1 H) 5.17-5.35 (m, 1 H) 4.79 (dd, J=7.92, 3.62 Hz, 1 H) 3.32-3.58 (m, 2 H) 2.44 (tt, J=10.03, 3.08 Hz, 2 H) 1.45 (s, 6 H).

Aufarbeitung

  1. extractionextracted with EtOAc
  2. concentrationEtOAc was concentrated
  3. customresidue purified with ISCO
  4. washeluting with 0-100% EtOAc/hexanes

Quellen und Nachweise

ORD-Eintrag
ord-85d3c7d0548142238e399fc87b332d74
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09174992B2

Notizen zur Reaktion

Wird geladen…