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Sodium Carbonate → tert-butyl 4-(4-{3-[3-({[(2,2,2-trifluoroethyl)amino]carbonyl}amino)phenyl]imidazo[1,2-b]pyridazin-7-yl}-1H-pyrazol-1-yl)piperidine-1-carboxylate

HRID 407004
ノート
印刷プレビュー

反応式

HRID 407004 の反応式
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[N:11][N:12]([CH:14]3[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]3)[CH:13]=2)O1.Cl[C:29]1[CH:34]=[N:33][N:32]2[C:35]([C:38]3[CH:39]=[C:40]([NH:44][C:45]([NH:47][CH2:48][C:49]([F:52])([F:51])[F:50])=[O:46])[CH:41]=[CH:42][CH:43]=3)=[CH:36][N:37]=[C:31]2[CH:30]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:52][C:49]([F:50])([F:51])[CH2:48][NH:47][C:45]([NH:44][C:40]1[CH:39]=[C:38]([C:35]2[N:32]3[N:33]=[CH:34][C:29]([C:9]4[CH:10]=[N:11][N:12]([CH:14]5[CH2:15][CH2:16][N:17]([C:20]([O:22][C:23]([CH3:24])([CH3:25])[CH3:26])=[O:21])[CH2:18][CH2:19]5)[CH:13]=4)=[CH:30][C:31]3=[N:37][CH:36]=2)[CH:43]=[CH:42][CH:41]=1)=[O:46]
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

8

反応物 3

HCID 10340Sodium CarbonateHCID 45480279tert-butyl 4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylateHCID 67980172N-[3-(7-chloroimidazo[1,2-b]pyridazin-3-yl)phenyl]-N'-(2,2,2-trifluoroethyl)urea

生成物 1

HCID 67980046tert-butyl 4-(4-{3-[3-({[(2,2,2-trifluoroethyl)amino]carbonyl}amino)phenyl]imidazo[1,2-b]pyridazin-7-yl}-1H-pyrazol-1-yl)piperidine-1-carboxylate収率 82.5%

試薬・触媒・溶媒 4

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

A mixture of tert-butyl 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylate (0.830 g, 2.20 mmol, Combi-Block, Cat. No. FM-2957), N-[3-(7-chloroimidazo[1,2-b]pyridazin-3-yl)phenyl]-N′-(2,2,2-trifluoroethyl)urea (0.739 g, 2.00 mmol), tetrakis(triphenylphosphine)palladium(0) (116 mg, 0.100 mmol) and sodium carbonate (0.636 g, 6.00 mmol) in dioxane (15 mL) and water (5 mL) was degassed and recharged with nitrogen three times, and heated and stirred at 100° C. overnight. After cooling, the mixture was diluted with ethyl acetate, washed with water and brine. The organic layer was dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column with ethyl acetate in hexane (gradient: 0-50%) to afford the desired product (0.965 g, 82.5%). LCMS (M+H)+: m/z=585.2.

後処理

  1. temperatureheated
  2. temperatureAfter cooling
  3. washwashed with water and brine
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by flash chromatography on a silica gel column with ethyl acetate in hexane (gradient: 0-50%)

出典と根拠

ORDレコード
ord-a6a47ed9a7a5477ab61bf98021739ba4
出典データセット
uspto-grants-2014_06
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08754114B2

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