Potassium Carbonate → HCID 67479155、化合物

HRID 1890018ノート

反応式

HRID 1890018 の反応式
[NH2:1][C:2]1[N:11]=[C:5]2[C:6]([OH:10])=[CH:7][CH:8]=[CH:9][N:4]2[N:3]=1.Br[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[CH:15]=1.C(=O)([O-])[O-].[K+].[K+]>CC(C)=O.O.ClCCl>[Cl:20][C:16]1[CH:15]=[C:14]([CH:19]=[CH:18][CH:17]=1)[CH2:13][O:10][C:6]1[C:5]2[N:4]([N:3]=[C:2]([NH2:1])[N:11]=2)[CH:9]=[CH:8][CH:7]=1

参加物

7

反応物 3

HCID 11430Potassium CarbonateHCID 698381-(Bromomethyl)-3-chlorobenzeneHCID 67481450HCID 67481450、化合物

生成物 1

HCID 67479155HCID 67479155、化合物

試薬・触媒・溶媒 3

HCID 180Acetone溶媒HCID 962Water溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
80 °C

実験手順

260 a)N-(3-Hydroxy-2-pyridinyl)-N′-carboethoxy-thiourea was prepared from 2-amino-pyridin-3-ol (4.00 g, 0.0363 mol) in a manner analogous to Example 2a. The product of the reaction was isolated as a yellow solid. 260 b) 2-Amino-[1,2,4]triazolo[1,5-a]pyridin-8-ol was prepared from N-(3-hydroxy-2-pyridinyl)-N′-carboethoxy-thiourea (1.8 g, 5.9 mmol) in a manner analogous to Example 2b. Product was isolated as a beige solid (3.17 g, 58%). 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 10.18 (bs, 1H), 8.02 (dd, J=6.41 Hz, 1.2 Hz, 1H), 6.71-6.64 (m, 2H), 5.79 (bs, 2H). MS=151.0 (MH)+. 260 c) 2-Amino-[1,2,4]triazolo[1,5-a]pyridin-8-ol (0.200 g, 1.33 mmol) was suspended in acetone (1.9 mL). 1-(bromomethyl)-3-chloro-benzene (0.184 mL, 1.40 mmol) and potassium carbonate (193 mg, 1.40 mmol) were added and the reaction mixture was heated to 80° C. for 1 hour. Reaction mixture was cooled to room temperature, diluted with water, extracted with dichloromethane, dried over magnesium sulfate, filtered, and concentrated. Resulting oil was taken up in dichloromethane and purified via chromatography (silica gel 0-100% ethyl acetate in hexanes). 8-(3-Chloro-benzyloxy)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine was isolated as an oil which solidified on standing. 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 8.17 (d, J=6.6 Hz, 1H), 7.56 (s, 1H), 7.44-7.42 (m, 3H), 6.99 (d, J=7.9 Hz, 1H), 6.79-6.75 (m, 1H), 5.94 (bs, 2H), 5.30 (s, 2H). MS=275 (MH)+. 260 d) [8-(3-Chloro-benzyloxy)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine was prepared from 8-(3-chloro-benzyloxy)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine (95.0 mg, 0.346 mmol) and 1-(4-bromo-phenyl)-4-methyl-piperazine (102 mg, 0.399 mmol in a manner analogous to Example 2d. Product was isolated as a pale orange solid (0.073 g, 47%). MP=135-138° C. 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 9.33 (s, 1H), 8.37 (d, J=6.7 Hz, 1H), 7.58 (s, 1H), 7.51-7.44 (m, 5H), 7.09 (d, J=7.9 Hz, 1H), 6.91-6.86 (m, 3H), 5.35 (s, 2H), 3.04-3.01 (m, 4H), 2.46-2.44 (m, 4H), 2.22 (s, 3H). MS=449 (MH)+.

後処理

  1. customReaction mixture
  2. temperaturewas cooled to room temperature
  3. extractionextracted with dichloromethane
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customResulting oil
  8. custompurified via chromatography (silica gel 0-100% ethyl acetate in hexanes)

出典と根拠

ORDレコード
ord-0eec826e6c5a4832b11481b0c8ab49a5
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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