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Hydrochloric Acid → 5-cyclopropyl-2-(4-hydroxyphenyl)-6-[(3-hydroxypropyl)(methylsulfonyl)amino]-N-methyl-2H-indazole-3-carboxamide

HRID 1037544
ノート
印刷プレビュー

反応式

HRID 1037544 の反応式
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]([C:17]([NH:19][CH3:20])=[O:18])=[C:15]3[C:10]([CH:11]=[C:12]([N:24]([CH2:29][CH2:30][CH2:31][OH:32])[S:25]([CH3:28])(=[O:27])=[O:26])[C:13]([CH:21]4[CH2:23][CH2:22]4)=[CH:14]3)=[N:9]2)=[CH:4][CH:3]=1.[OH-:33].[K+].Cl>O1CCOCC1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:21]1([C:13]2[C:12]([N:24]([CH2:29][CH2:30][CH2:31][OH:32])[S:25]([CH3:28])(=[O:27])=[O:26])=[CH:11][C:10]3[C:15](=[C:16]([C:17]([NH:19][CH3:20])=[O:18])[N:8]([C:5]4[CH:6]=[CH:7][C:2]([OH:33])=[CH:3][CH:4]=4)[N:9]=3)[CH:14]=2)[CH2:23][CH2:22]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 3

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 569627692-(4-bromophenyl)-5-cyclopropyl-6-[3-hydroxypropyl(methylsulfonyl)amino]-N-methyl-indazole-3-carboxamide

生成物 1

HCID 675170055-cyclopropyl-2-(4-hydroxyphenyl)-6-[(3-hydroxypropyl)(methylsulfonyl)amino]-N-methyl-2H-indazole-3-carboxamide収率 109%

試薬・触媒・溶媒 3

HCID 9811564
Bis(dibenzylideneacetone)palladium
触媒
HCID 962Water溶媒
HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

2-(4-Bromophenyl)-5-cyclopropyl-6-[(3-hydroxypropyl)(methylsulfonyl)amino]-N-methyl-2H-indazole-3-carboxamide (i) (16 mg, 0.031 mmol) in 1,4-dioxane (0.5 mL) had a solution of potassium hydroxide (9 mg, 0.016 mmol) in water (0.5 mL) added and was degassed. tert-Butyl-XPhos (4 mg, 0.009 mmol) and Pd2(dba)3 (4 mg, 0.004 mmol) were added and the reaction was heated at 100° C. for 4 h. The mixture was cooled to RT, 1 M hydrochloric acid (0.5 mL) was added and this was then concentrated to dryness. The residue was purified by reverse phase flash column chromatography eluting with ACN/water (5-100%) to afford 5-cyclopropyl-2-(4-hydroxyphenyl)-6-[(3-hydroxypropyl)(methylsulfonyl)amino]-N-methyl-2H-indazole-3-carboxamide (ii) as a white solid (8 mg, 57%).

後処理

  1. additionadded
  2. customwas degassed
  3. temperatureThe mixture was cooled to RT
  4. concentrationthis was then concentrated to dryness
  5. customThe residue was purified by reverse phase flash column chromatography
  6. washeluting with ACN/water (5-100%)

出典と根拠

ORDレコード
ord-f2eb5e5fd6be498d88f4ce788ba5ee69
出典データセット
uspto-grants-2013_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08546389B2

反応ノート

読み込み中…

このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート