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Hydrochloric Acid → 6-[(1,1-Dioxido-4-thiomorpholinyl)methyl]-N-[6-(1H-indol-4-yl)-1H-indazol-4-yl]-2-pyridinecarboxamide

HRID 520658
ノート
印刷プレビュー

反応式

HRID 520658 の反応式
Cl[CH2:2][C:3]1[N:8]=[C:7]([C:9]([NH:11][C:12]2[CH:20]=[C:19]([C:21]3[CH:29]=[CH:28][CH:27]=[C:26]4[C:22]=3[CH:23]=[CH:24][NH:25]4)[CH:18]=[C:17]3[C:13]=2[CH:14]=[N:15][N:16]3S(C2C=CC=CC=2)(=O)=O)=[O:10])[CH:6]=[CH:5][CH:4]=1.[NH:39]1[CH2:44][CH2:43][S:42](=[O:46])(=[O:45])[CH2:41][CH2:40]1.[I-].[Na+].CCN(C(C)C)C(C)C.Cl>CC#N>[O:45]=[S:42]1(=[O:46])[CH2:43][CH2:44][N:39]([CH2:2][C:3]2[N:8]=[C:7]([C:9]([NH:11][C:12]3[CH:20]=[C:19]([C:21]4[CH:29]=[CH:28][CH:27]=[C:26]5[C:22]=4[CH:23]=[CH:24][NH:25]5)[CH:18]=[C:17]4[C:13]=3[CH:14]=[N:15][NH:16]4)=[O:10])[CH:6]=[CH:5][CH:4]=2)[CH2:40][CH2:41]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

7

反応物 5

HCID 313Hydrochloric AcidHCID 5238Sodium IodideHCID 81531DiisopropylethylamineHCID 6484228Thiomorpholine 1,1-dioxideHCID 582679866-(Chloromethyl)-N-[6-(1H-indol-4-yl)-1-(phenylsulfonyl)-1H-indazol-4-yl]-2-pyridinecarboxamide

生成物 1

HCID 53233540
6-[(1,1-Dioxido-4-thiomorpholinyl)methyl]-N-[6-(1H-indol-4-yl)-1H-indazol-4-yl]-2-pyridinecarboxamide

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

反応条件

温度
70 °C

実験手順

6-(Chloromethyl)-N-[6-(1H-indol-4-yl)-1-(phenylsulfonyl)-1H-indazol-4-yl]-2-pyridinecarboxamide (75 mg), thiomorpholine 1,1-dioxide (25 mg) and sodium iodide (25 mg) were added to a small round-bottomed flask followed by MeCN (2 ml) and DIPEA (0.048 ml). The reaction mixture was heated at 70° C. for 18 h. The reaction was cooled to RT and the solvent was removed under a stream of nitrogen. The residue was suspended in IPA (2 ml) and 2M NaOH (aq) (1 ml) was added. The mixture was stirred at RT for 2 h, heated to 50° C. for 1 h, then cooled to RT to remain stirring overnight. The reaction was heated to 60° C. for 1 h. Then 2M NaOH (aq) (0.5 ml) was added and reaction was stirred at 60° C. for 2 h. The reaction was neutralised with 2M HCl (aq.) and the solvent was removed in vacuo. The residue was dissolved in DMSO (3 ml), filtered and purified by MDAP (method K). The product-containing fractions were evaporated under a stream of nitrogen and the residues were taken up in methanol, combined and blown down to give title compound, 24 mg.

後処理

  1. temperatureThe reaction was cooled to RT
  2. customthe solvent was removed under a stream of nitrogen
  3. addition2M NaOH (aq) (1 ml) was added
  4. temperatureheated to 50° C. for 1 h
  5. temperaturecooled to RT
  6. stirringto remain stirring overnight
  7. temperatureThe reaction was heated to 60° C. for 1 h
  8. additionThen 2M NaOH (aq) (0.5 ml) was added
  9. customreaction
  10. stirringwas stirred at 60° C. for 2 h
  11. customthe solvent was removed in vacuo
  12. dissolutionThe residue was dissolved in DMSO (3 ml)
  13. filtrationfiltered
  14. custompurified by MDAP (method K)
  15. customThe product-containing fractions were evaporated under a stream of nitrogen

出典と根拠

ORDレコード
ord-be73252da59248b0a16cf7293e12b56a
出典データセット
uspto-grants-2016_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09326987B2

反応ノート

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