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

HRID 410377

반응식

HRID 410377 반응식
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

참가 물질

7

반응물 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

생성물 1

HCID 58456203N-[3-(5-thiazolyl)phenyl]-4-(trifluoromethyl)-2-Pyrimidinamine수율 73.7%

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매HCID 8857Ethyl Acetate용매

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온도
80 °C

실험 절차

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, 1 H). rhSYK activity=++.

후처리

  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

출처 및 근거

ORD 기록
ord-bed4e8d902094100addeac00a50457a7
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08759366B2

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