2-Amino-4-methylpyrimidine → 2,6-dichloro-N-(2-(4-methylpyrimidin-2-ylamino)pyridin-4-yl)benzamide

HRID 449879

Reaktionsgleichung

Reaktionsgleichung von HRID 449879
Br[C:2]1[CH:7]=[C:6]([NH:8][C:9](=[O:18])[C:10]2[C:15]([Cl:16])=[CH:14][CH:13]=[CH:12][C:11]=2[Cl:17])[CH:5]=[CH:4][N:3]=1.[NH2:19][C:20]1[N:25]=[C:24]([CH3:26])[CH:23]=[CH:22][N:21]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[Cl:17][C:11]1[CH:12]=[CH:13][CH:14]=[C:15]([Cl:16])[C:10]=1[C:9]([NH:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:19][C:20]2[N:25]=[C:24]([CH3:26])[CH:23]=[CH:22][N:21]=2)[CH:7]=1)=[O:18]

Komponenten

7

Edukt 4

HCID 79392-Amino-4-methylpyrimidineHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 75464886N-(2-Bromopyridin-4-yl)-2,6-dichlorobenzamide

Produkt 1

HCID 596180282,6-dichloro-N-(2-(4-methylpyrimidin-2-ylamino)pyridin-4-yl)benzamideAusbeute 12 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

To a microwave tube were added N-(2-bromopyridin-4-yl)-2,6-dichlorobenzamide (0.15 g, 0.43 mmol), 2-amino-4-methylpyrimidine (0.056 g, 0.52 mmol), Pd2(dba)3 (0.040 g, 0.043 mmol), XantPhos (0.050 g, 0.087 mmol), Cs2CO3 (0.28 g, 0.87 mmol) and dioxane (2 mL). The mixture was degassed with N2 for 10 min. The resulting mixture was irradiated in a microwave reactor at 140° C. for 3 hours and then cooled to room temperature. The mixture was filtered through Celite and concentrated under reduced pressure. The residue was dissolved in DMF and purified by prep-HPLC (Gilson GX 281, Shim-pack PRC-ODS 250 mm×20 mm×2, gradient: CH3CN/10 mm/L NH4HCO3, 17 min) to give the desired product as a white solid (19 mg, yield: 12%). 1H NMR (500 MHz, MeOH-d4): δ 8.88 (s, 1H), 8.36 (d, J=5.5 Hz, 1H), 8.16 (d, J=6.0 Hz, 1H), 7.64 (s, 1H), 7.45-7.38 (m, 4H), 6.85 (d, J=5.5 Hz, 1H), 2.50 (s, 3H). LCMS (ESI) m/z: 374.0 [M+H+].

Aufarbeitung

  1. customThe mixture was degassed with N2 for 10 min
  2. customThe resulting mixture was irradiated in a microwave reactor at 140° C. for 3 hours
  3. filtrationThe mixture was filtered through Celite
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe residue was dissolved in DMF
  6. custompurified by prep-HPLC (Gilson GX 281, Shim-pack PRC-ODS 250 mm×20 mm×2, gradient: CH3CN/10 mm/L NH4HCO3, 17 min)

Quellen und Nachweise

ORD-Eintrag
ord-95dd39581c024ef1831c1702d1149b35
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08486950B2

Verknüpfte Notizen

Wird geladen…