1-Fluoro-4-(methylsulphonyl)benzene → [1,2,4]Triazolo[1,5-a]pyridin-2-amine

HRID 1889987ノート

反応式

HRID 1889987 の反応式
[NH2:1][C:2]1[N:11]=[C:5]2[C:6](O)=[CH:7][CH:8]=[CH:9][N:4]2[N:3]=1.FC1C=CC(S(C)(=O)=O)=CC=1.CC(C)([O-])C.[K+]>CN(C)C(=O)C>[N:11]1[C:2]([NH2:1])=[N:3][N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12

参加物

5

反応物 3

HCID 679941-Fluoro-4-(methylsulphonyl)benzeneHCID 23665647Potassium tert-butoxideHCID 67481450HCID 67481450、化合物

生成物 1

HCID 584054[1,2,4]Triazolo[1,5-a]pyridin-2-amine

試薬・触媒・溶媒 1

HCID 31374Dimethylacetamide溶媒

反応条件

温度
130 °C

実験手順

A well stirred mixture of 2-amino-[1,2,4]triazolo[1,5-a]pyridine-8-ol (0.300 g, 2.00 mmol), 1-fluoro-4-methanesulfonyl-benzene (0.418 g, 2.40 mmol), N,N-dimethylacetamide (2 mL) and potassium tert-butoxide (0.448 g, 4.00 mmol) was heated at 130° C. for 18 h under an argon atmosphere. The reaction mixture was evaporated in vacuo and partitioned between dichloromethane and saturated aqueous sodium bicarbonate solution. The aqueous phase was extracted twice with dichloromethane and the combined organic layers were washed with brine, dried over sodium sulfate, filtered, and evaporated in vacuo to furnish a crude product. The crude product was purified by preparative Gilson HPLC method to yield a pure product, which was triturated from a mixture of dichloromethane, methanol, ether and hexane. 8-(4-Methanesulfonyl-phenoxy)-[1,2,4-triazolo[1,5-a]pyridin-2-ylamine was isolated as a white solid (125 mg, 20%). MP=245-247° C. 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 8.53 (d, J=6.56 Hz, 1H), 7.87 (d, J=8.77 Hz, 2H), 7.36 (d, J=7.73 Hz, 1H), 7.15 (d, J=8.76 Hz, 2H), 6.92 (t, J=7.28 Hz, 1H), 6.13 (s, 1H), 3.19 (s, 3H). MS=305 (MH)+. 211b) 2-Chloro-8-(4-methanesulfonyl-phenoxy)-[1,2,4]triazolo[1,5-a]pyridine was prepared in a manner analogous to Example 68a. Product was isolated as a yellow solid (0.455 g, 80%). MP=202-204° C. 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 8.44 (d, J=6.77 Hz, 1H), 7.98 (d, J=8.08 Hz, 2H), 7.21 (t, J=7.76 Hz, 3H), 7.08 (t, J=7.52 Hz, 1H), 3.09 (s, 3H). MS=324 (MH)+. 211c) (1-Ethyl-1H-pyrazol-4-yl)-[8-(4-methanesulfonyl-phenoxy)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-amine was prepared from 2-chloro-8-(4-methanesulfonyl-phenoxy)-[1,2,4]triazolo[1,5-a]pyridine (0.065 g, 0.20 mmol) and 1-ethyl-1H-pyrazol-4-ylamine (0.029 g, 0.26 mmol) in a manner analogous to Example 2d. Product was isolated as a tan solid (45 mg, 56%). MP=183-185° C. 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 9.27 (s, 1H), 8.67 (d, J=6.51 Hz, 1H), 7.89 (d, J=7.72 Hz, 2H), 7.68 (s, 1H), 7.45 (d, J=7.74 Hz, 1H), 7.35 (s, 1H), 7.22 (d, J=7.29 Hz, 2H), 7.00 (t, J=7.29 Hz, 1H), 4.055 (q, J=7.18 Hz, 2H), 3.20 (s, 3H), 1.32 (t, J=7.06 Hz, 3H). MS=399 (MH)+.

後処理

  1. customThe reaction mixture was evaporated in vacuo
  2. custompartitioned between dichloromethane and saturated aqueous sodium bicarbonate solution
  3. extractionThe aqueous phase was extracted twice with dichloromethane
  4. washthe combined organic layers were washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customto furnish a crude product
  9. customThe crude product was purified by preparative Gilson HPLC method
  10. customto yield a pure product, which
  11. customwas triturated from a mixture of dichloromethane, methanol, ether and hexane

出典と根拠

ORDレコード
ord-f3778f77d431428cb753c6d1985c1749
出典データセット
uspto-grants-2013_08
特許番号
US08501936B2

反応ノート

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