Sodium Bicarbonate → Trifluoroacetic acid

HRID 58079

Reaktionsgleichung

Reaktionsgleichung von HRID 58079
CC1(C)C(C)(C)OB([C:9]2[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[C:14]3[C:10]=2[CH:11]=[N:12][NH:13]3)O1.Br[C:24]1[CH:25]=[N:26][N:27]([CH3:31])[C:28]=1[CH2:29][OH:30].[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:18]([F:21])([F:20])[F:19])=[O:33].[CH3:31][N:27]1[C:28]([CH2:29][OH:30])=[C:24]([C:9]2[CH:17]=[C:16]([C:18]([F:19])([F:20])[F:21])[CH:15]=[C:14]3[C:10]=2[CH:11]=[N:12][NH:13]3)[CH:25]=[N:26]1

Komponenten

7

Edukt 3

HCID 516892Sodium BicarbonateHCID 57415773(4-bromo-1-methyl-1H-pyrazol-5-yl)methanolHCID 897828064-(Tetramethyl-1,3,2-dioxaborolan-2-yl)-6-(trifluoromethyl)-1H-indazole

Produkt 2

HCID 6422Trifluoroacetic acidHCID 89783009(1-methyl-4-(6-(trifluoromethyl)-1H-indazol-4-yl)-1H-pyrazol-5-yl)methanol

Reagenzien, Katalysatoren, Lösungsmittel 2

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

Reaktionsbedingungen

Temperatur
140 °C

Versuchsvorschrift

A vial was charged with a mixture of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6-(trifluoromethyl)-1H-indazole (0.1 g, 0.320 mmol), (4-bromo-1-methyl-1H-pyrazol-5-yl)methanol (0.086 g, 0.449 mmol) and PdCl2(dppf) (0.012 g, 0.016 mmol) in dioxane (8 mL) and aqueous saturated NaHCO3 (2 mL). The resulting light brown suspension was heated at 140° C. for 45 minutes in a microwave reactor. The reaction mixture was subsequently concentrated and the crude residue was purified by preparative HPLC, eluting with 30% ACN (containing 0.035% TFA) in H2O (containing 0.05% TFA) over a period of 6 minutes. The product-containing fractions were combined and volatiles removed in vacuo to give a TFA salt of the title compound as an off white solid (8 mg, 8%). 1H NMR (400 MHz, DMSO-d6) δ ppm 3.96 (s, 3H), 4.56 (d, J=4.80 Hz, 2H), 5.53 (t, J=4.93 Hz, 1H), 7.43 (s, 1H), 7.78-7.92 (m, 2H), 8.30 (s, 1H), 13.62 (s, 1H); ESI-MS m/z [M+H]+ calc'd for C13H11F3N4O, 297.1. found 297.14.

Aufarbeitung

  1. concentrationThe reaction mixture was subsequently concentrated
  2. customthe crude residue was purified by preparative HPLC
  3. washeluting with 30% ACN (containing 0.035% TFA) in H2O (containing 0.05% TFA) over a period of 6 minutes
  4. customvolatiles removed in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-97d646ad632144968d0bda4f93d8203b
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09434743B2

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