Cesium carbonate → 1-(2-Cyclopropylpyridin-4-yl)-4-fluoro-1-(2-(pyrimidin-5-yl)pyridin-4-yl)-1H-isoindol-3-amine

HRID 1662271Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1662271
Br[C:2]1[CH:7]=[C:6]([C:8]2([C:19]3[CH:24]=[CH:23][N:22]=[C:21]([CH:25]4[CH2:27][CH2:26]4)[CH:20]=3)[C:16]3[C:11](=[C:12]([F:17])[CH:13]=[CH:14][CH:15]=3)[C:10]([NH2:18])=[N:9]2)[CH:5]=[CH:4][N:3]=1.[N:28]1[CH:33]=[C:32](B(O)O)[CH:31]=[N:30][CH:29]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>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].COCCOC.CCO.O>[CH:25]1([C:21]2[CH:20]=[C:19]([C:8]3([C:6]4[CH:5]=[CH:4][N:3]=[C:2]([C:32]5[CH:33]=[N:28][CH:29]=[N:30][CH:31]=5)[CH:7]=4)[C:16]4[C:11](=[C:12]([F:17])[CH:13]=[CH:14][CH:15]=4)[C:10]([NH2:18])=[N:9]3)[CH:24]=[CH:23][N:22]=2)[CH2:27][CH2:26]1

Komponenten

6

Edukt 3

HCID 10796Cesium carbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 585794871-(2-Bromopyridin-4-yl)-1-(2-cyclopropylpyridin-4-yl)-4-fluoro-1H-isoindol-3-amine

Produkt 1

HCID 462030761-(2-Cyclopropylpyridin-4-yl)-4-fluoro-1-(2-(pyrimidin-5-yl)pyridin-4-yl)-1H-isoindol-3-amineAusbeute 50,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 86587095Dimethoxyethane ethanol waterLösungsmittel

Reaktionsbedingungen

Temperatur
150 °C

Versuchsvorschrift

1-(2-Bromopyridin-4-yl)-1-(2-cyclopropylpyridin-4-yl)-4-fluoro-1H-isoindol-3-amine (92 mg, 0.22 mmol), 5-pyrimidinylboronic acid (35.0 mg, 0.28 mmol), [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) chloride (8.87 mg, 10.87 μmol), cesium carbonate (0.052 mL, 0.65 mmol) and DME:EtOH:water (6:3:1) (3.00 mL) were put in a microwave vial and heated at 150° C. in a microwave reactor for 20 min. The mixture was filtered through a syringe filter and purified by prep-HPLC. The desired fractions were pooled and concentrated in vacuo. The residue was redissolved in acetonitrile and water was added. The mixture was freeze dried to give the title compound (46.9 mg, 47%). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.33 (s, 2 H) 9.24 (s, 1 H) 8.67 (d, 1 H) 8.29 (d, 1 H) 7.96 (d, 1 H) 7.87 (d, 1 H) 7.58 (td, 1 H) 7.46 (dd, 1 H) 7.31 (dd, 1 H) 7.21 (d, 1 H) 7.03 (dd, 1 H) 6.79 (br. s., 2 H) 1.96-2.07 (m, 1 H) 0.80-0.96 (m, 4 H); MS (ES+) m/z 423 [M+1]+.

Aufarbeitung

  1. filtrationThe mixture was filtered through a syringe
  2. filtrationfilter
  3. custompurified by prep-HPLC
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue was redissolved in acetonitrile
  6. additionwater was added
  7. customdried

Quellen und Nachweise

ORD-Eintrag
ord-b12ebb92d9a94f568f099d553007cbd9
Quelldatensatz
uspto-grants-2011_10
Patentnummer
US08030500B2

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