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Ammonia → 1-(6-{[6-(4-Fluorophenyl)-7,8-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl]sulphanyl}-1,3-benzothiazol-2-yl)-3-[2-(morpholin-4-yl)ethyl]urea

HRID 517815
ノート
印刷プレビュー

反応式

HRID 517815 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11]3[N:12]([C:14]([S:17][C:18]4[CH:38]=[CH:37][C:21]5[N:22]=[C:23]([NH:25][C:26]([NH:28][CH2:29][CH2:30][N:31]6[CH2:36][CH2:35][O:34][CH2:33][CH2:32]6)=[O:27])[S:24][C:20]=5[CH:19]=4)=[N:15][N:16]=3)[N:13]=2)=[CH:4][CH:3]=1.N>C(O)(=O)C.[Zn]>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH2:9][CH2:10][C:11]3[N:12]([C:14]([S:17][C:18]4[CH:38]=[CH:37][C:21]5[N:22]=[C:23]([NH:25][C:26]([NH:28][CH2:29][CH2:30][N:31]6[CH2:36][CH2:35][O:34][CH2:33][CH2:32]6)=[O:27])[S:24][C:20]=5[CH:19]=4)=[N:15][N:16]=3)[N:13]=2)=[CH:4][CH:3]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

5

反応物 2

HCID 222AmmoniaHCID 25182860Sar-125844

生成物 1

HCID 425988921-(6-{[6-(4-Fluorophenyl)-7,8-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl]sulphanyl}-1,3-benzothiazol-2-yl)-3-[2-(morpholin-4-yl)ethyl]urea収率 22.9%

試薬・触媒・溶媒 2

HCID 23994Zinc触媒2 回HCID 176Acetic Acid溶媒

反応条件

温度
20 °C

実験手順

A mixture of 209 mg of 1-(6-{[6-(4-fluorophenyl)[1,2,4]triazolo[4,3-b]pyridazin-3-yl]sulphanyl}-1,3-benzothiazol-2-yl)-3-(2-morpholin-4-ylethyl)urea and 241 mg of zinc in 7 cm3 of acetic acid is stirred at 20° C. for 1.5 h and then heated at 50° C. for 3.5 h. 241 mg of zinc are again added and the mixture is again left for 1 h at 50° C. After stirring overnight at 20° C., aqueous ammonia is added so that the reaction mixture changes to an alkaline pH. This mixture is extracted with ethyl acetate. The organic phase is washed with a saturated solution of sodium bicarbonate and then with brine and is then dried with magnesium sulphate and evaporated to dryness under vacuum. The residue is purified by chromatography on a Merck cartridge of 25 g of silica 15-40 μm by solid deposit, elution being carried out with a 9/1 mixture of dichloromethane/(dichloromethane:38/methanol:17/aqueous ammonia:2). 48 mg of 1-(6-{[6-(4-fluorophenyl)-7,8-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl]sulphanyl}-1,3-benzothiazol-2-yl)-3-[2-(morpholin-4-yl)ethyl]urea are thus obtained in the form of a white solid, the characteristics of which are as follows:

後処理

  1. temperatureheated at 50° C. for 3.5 h
  2. waitthe mixture is again left for 1 h at 50° C
  3. stirringAfter stirring overnight at 20° C.
  4. extractionThis mixture is extracted with ethyl acetate
  5. washThe organic phase is washed with a saturated solution of sodium bicarbonate
  6. dry with materialwith brine and is then dried with magnesium sulphate
  7. customevaporated to dryness under vacuum
  8. customThe residue is purified by chromatography on a Merck cartridge of 25 g of silica 15-40 μm by solid deposit, elution
  9. additionbeing carried out with a 9/1 mixture of dichloromethane/(dichloromethane:38/methanol:17/aqueous ammonia:2)

出典と根拠

ORDレコード
ord-f1c0fc9605254bd09eddd265aa830632
出典データセット
uspto-grants-2015_08
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09115134B2

反応ノート

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