Sodium Carbonate → N-(3-methyl-5-{2-[2-(methylsulfonyl)propan-2-yl]-1,3-thiazol-5-yl}phenyl)-4-(trifluoromethyl)pyrimidin-2-amine

HRID 1040087

Reaktionsgleichung

Reaktionsgleichung von HRID 1040087
Br[C:2]1[S:6][C:5]([C:7]([S:10]([CH3:13])(=[O:12])=[O:11])([CH3:9])[CH3:8])=[N:4][CH:3]=1.[CH3:14][C:15]1[CH:16]=[C:17]([NH:30][C:31]2[N:36]=[C:35]([C:37]([F:40])([F:39])[F:38])[CH:34]=[CH:33][N:32]=2)[CH:18]=[C:19](B2OC(C)(C)C(C)(C)O2)[CH:20]=1.O1CCOCC1.C([O-])([O-])=O.[Na+].[Na+]>O.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(Cl)Cl>[CH3:14][C:15]1[CH:16]=[C:17]([NH:30][C:31]2[N:36]=[C:35]([C:37]([F:39])([F:38])[F:40])[CH:34]=[CH:33][N:32]=2)[CH:18]=[C:19]([C:2]2[S:6][C:5]([C:7]([S:10]([CH3:13])(=[O:12])=[O:11])([CH3:9])[CH3:8])=[N:4][CH:3]=2)[CH:20]=1

Komponenten

7

Edukt 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 58456089N-(3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4-(trifluoromethyl)pyrimidin-2-amine2×HCID 672585745-Bromo-2-[2-(methylsulfonyl)propan-2-yl]-1,3-thiazole

Produkt 1

HCID 58456079N-(3-methyl-5-{2-[2-(methylsulfonyl)propan-2-yl]-1,3-thiazol-5-yl}phenyl)-4-(trifluoromethyl)pyrimidin-2-amineAusbeute 78 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418807HCID 178418807, VerbindungKatalysatorHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

The product of Step 1 (112 mg, 0.40 mmol), N-[3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (Intermediate 3, 150 mg, 0.40 mmol), and PdCl2(dppf)-CH2Cl2 (29 mg, 0.040 mmol) were combined in a flask, sealed, and purged with nitrogen (2×). Dioxane (2.4 mL) and 2 M Na2CO3 (0.59 mL, 1.19 mmol) were added, and the reaction was purged again with nitrogen (2×). The mixture was stirred in an oil bath at 100° C. overnight. The dark brown reaction was diluted with water and extracted with ethyl acetate (2×). The combined organic layers were washed with brine, dried (MgSO4), filtered and evaporated. Flash chromatography (0-50% ethyl acetate in hexanes) afforded N-(3-methyl-5-{2-[2-(methylsulfonyl)propan-2-yl]-1,3-thiazol-5-yl}phenyl)-4-(trifluoromethyl)pyrimidin-2-amine (140 mg, 78%) as a colorless solid. MS ESI: [M+H]+ m/z 457.0. 1H NMR (500 MHz, DMSO-d6) δ 10.29 (s, 1H), 8.84 (d, J=4.9, 1H), 8.16 (s, 1H), 8.03 (s, 1H), 7.49 (s, 1H), 7.29 (d, J=4.9, 1H), 7.22 (s, 1H), 2.96 (s, 3H), 2.32 (s, 3H), 1.83 (s, 6H). rhSYK activity=+++

Aufarbeitung

  1. customsealed
  2. custompurged with nitrogen (2×)
  3. customthe reaction was purged again with nitrogen (2×)
  4. customThe dark brown reaction
  5. extractionextracted with ethyl acetate (2×)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. customevaporated

Quellen und Nachweise

ORD-Eintrag
ord-5903ff244a374b609427751619d83dbb
Quelldatensatz
uspto-grants-2013_10
Patentnummer
US08551984B2

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