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

HRID 410377ノート

反応式

HRID 410377 の反応式
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

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
80 °C

実験手順

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=++.

後処理

  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

出典と根拠

ORDレコード
ord-bed4e8d902094100addeac00a50457a7
出典データセット
uspto-grants-2014_06
特許番号
US08759366B2

反応ノート

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