Sodium Bicarbonate → HCID 89794891, Verbindung

HRID 58119

Reaktionsgleichung

Reaktionsgleichung von HRID 58119
Br[C:2]1[CH:3]=[CH:4][C:5]([N:9]2[CH2:14][CH2:13][NH:12][C@H:11]([CH3:15])[CH2:10]2)=[N:6][C:7]=1[CH3:8].[F:16][C:17]([F:31])([F:30])[C:18]1[CH:26]=[C:25]2[C:21]([CH:22]=[N:23][NH:24]2)=[C:20](B(O)O)[CH:19]=1.[C:32]([O-:35])(O)=[O:33].[Na+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:32]([OH:35])([C:17]([F:31])([F:30])[F:16])=[O:33].[CH3:8][C:7]1[C:2]([C:20]2[CH:19]=[C:18]([C:17]([F:31])([F:30])[F:16])[CH:26]=[C:25]3[C:21]=2[CH:22]=[N:23][NH:24]3)=[CH:3][CH:4]=[C:5]([N:9]2[CH2:14][CH2:13][NH:12][C@H:11]([CH3:15])[CH2:10]2)[N:6]=1

Komponenten

7

Edukt 3

HCID 516892Sodium BicarbonateHCID 89783507HCID 89783507, VerbindungHCID 89794907(R)-1-(5-bromo-6-methylpyridin-2-yl)-3-methylpiperazine

Produkt 2

HCID 6422Trifluoroacetic acidHCID 89794891HCID 89794891, VerbindungAusbeute 29,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
145 °C

Versuchsvorschrift

In a 10 mL microwave vial were mixed (R)-1-(5-bromo-6-methylpyridin-2-yl)-3-methylpiperazine (120 mg, 0.444 mmol), (6-(trifluoromethyl)-1H-indazol-4-yl)boronic acid (133 mg, 0.577 mmol), PdCl2(dppf) (32.5 mg, 0.044 mmol), and aqueous NaHCO3 (0.950 mL, 1.777 mmol) in dioxane (10 mL) to give an orange suspension. The vial was sealed and heated in a microwave reactor to 145° C. for 45 minutes. The reaction mixture was then filtered and the product was purified by preparative HPLC, eluting with a gradient of 15-40% ACN (containing 0.035% TFA) in H2O (containing 0.05% TFA). The pure fractions were lyophilized to give a TFA salt of the title compound as a white solid (31.6 mg, 14.5%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.31 (d, J=6.57 Hz, 3H), 2.27 (s, 3H), 2.95 (dd, J=14.02, 10.48 Hz, 1H), 3.05-3.21 (m, 2H), 3.36 (d, J=7.33 Hz, 1H), 3.44 (d, J=11.62 Hz, 1H), 4.44 (d, J=13.14 Hz, 2H), 6.94 (d, J=8.59 Hz, 1H), 7.24 (d, J=1.52 Hz, 1H), 7.64 (d, J=8.59 Hz, 1H), 7.92-7.94 (m, 1H), 7.95 (d, J=1.01 Hz, 1H), 8.77 (d, J=8.59 Hz, 1H), 9.10 (d, J=8.34 Hz, 1H); ESI-MS m/z [M+H]+ calc'd for C19H20F3N5, 376.2. found 376.4.

Aufarbeitung

  1. customto give an orange suspension
  2. customThe vial was sealed
  3. filtrationThe reaction mixture was then filtered
  4. customthe product was purified by preparative HPLC
  5. washeluting with a gradient of 15-40% ACN (containing 0.035% TFA) in H2O (containing 0.05% TFA)

Quellen und Nachweise

ORD-Eintrag
ord-3b6739e8385a46cda3900b530fb52374
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09434743B2

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