Sodium Carbonate → N-[3-(5-thiazolyl)phenyl]-4-(trifluoromethyl)-2-Pyrimidinamine

HRID 1039867Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1039867
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[C:11]([NH:15][C:16]3[N:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[CH:18][N:17]=3)[CH:12]=[CH:13][CH:14]=2)O1.Br[C:28]1[S:32][CH:31]=[N:30][CH:29]=1.C(=O)([O-])[O-].[Na+].[Na+]>O.CCOC(C)=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]>[S:32]1[C:28]([C:9]2[CH:10]=[C:11]([NH:15][C:16]3[N:21]=[C:20]([C:22]([F:23])([F:24])[F:25])[CH:19]=[CH:18][N:17]=3)[CH:12]=[CH:13][CH:14]=2)=[CH:29][N:30]=[CH:31]1

Komponenten

7

Edukt 3

HCID 10340Sodium CarbonateHCID 5460595-BromothiazoleHCID 58456307N-(3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4-(trifluoromethyl)pyrimidin-2-amine

Produkt 1

HCID 58456203N-[3-(5-thiazolyl)phenyl]-4-(trifluoromethyl)-2-PyrimidinamineAusbeute 73,7 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

Pd(dppf)Cl2 (1.01 g, 1.23 mmol) and Intermediate 6 (9.0 g, 25 mmol) were combined in a flask and were evacuated and back-filled with nitrogen (×3). Added 2-Me THF (90 mL), 5-bromothiazole (4.45 g, 27.1 mmol), and aqueous sodium carbonate (24.7 mL, 49.3 mmol) sequentially. Sealed the flask and heated to 80° C. for 15 h. The brown solution was allowed to cool to rt, then diluted with water and EtOAc. The layers were separated, and the aqueous portion was extracted with EtOAc (2×). The combined organic portions were washed with saturated aqueous NaHCO3, then Brine, then dried over Na2SO4 and concentrated in vacuo. Trituration with CH2Cl2 and collection of the beige solid via filtration provided 5.94 g of the desired product. The mother liquor was concentrated in vacuo and subsequent purification via silica gel column chromatography (CH2Cl2-40% EtOAc:CH2Cl2) provided an additional 1.41 g of the desired product. In total, N-[3-(1,3-thiazol-5-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (7.35 g, 22.8 mmol, 93%) was isolated as a beige solid. MS APCI: [M+H]+ m/z 323. 1H NMR (600 MHz, DMSO-D6, ppm) δ 10.32 (s, 1H), 9.06 (s, 1H), 8.82 (d, J=4.8, 1H), 8.20 (d, J=8.2, 1H), 8.20 (s, 1H), 7.64 (d, J=7.5, 1H), 7.40-7.31 (m, 2H), 7.27 (d, J=4.9, 1H). rhSYK activity=++.

Aufarbeitung

  1. customwere evacuated
  2. additionback-filled with nitrogen (×3)
  3. customSealed the flask
  4. temperatureto cool to rt
  5. customThe layers were separated
  6. extractionthe aqueous portion was extracted with EtOAc (2×)
  7. washThe combined organic portions were washed with saturated aqueous NaHCO3
  8. dry with materialBrine, then dried over Na2SO4
  9. concentrationconcentrated in vacuo
  10. customTrituration with CH2Cl2 and collection of the beige solid
  11. filtrationvia filtration

Quellen und Nachweise

ORD-Eintrag
ord-ad149497847a4829a0de8470394dd6ae
Quelldatensatz
uspto-grants-2013_10
Patentnummer
US08551984B2

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