Sodium Carbonate → Tert-butyl 4-(5-{3-[3-({[(2,2,2-trifluoroethyl)amino]carbonyl}amino)phenyl]imidazo[1,2-b]pyridazin-7-yl}pyridin-2-yl)piperazine-1-carboxylate

HRID 407022ノート

反応式

HRID 407022 の反応式
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[CH:11][C:12]([N:15]3[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]3)=[N:13][CH:14]=2)O1.Cl[C:30]1[CH:35]=[N:34][N:33]2[C:36]([C:39]3[CH:40]=[C:41]([NH:45][C:46]([NH:48][CH2:49][C:50]([F:53])([F:52])[F:51])=[O:47])[CH:42]=[CH:43][CH:44]=3)=[CH:37][N:38]=[C:32]2[CH:31]=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:53][C:50]([F:51])([F:52])[CH2:49][NH:48][C:46]([NH:45][C:41]1[CH:40]=[C:39]([C:36]2[N:33]3[N:34]=[CH:35][C:30]([C:9]4[CH:10]=[CH:11][C:12]([N:15]5[CH2:16][CH2:17][N:18]([C:21]([O:23][C:24]([CH3:25])([CH3:26])[CH3:27])=[O:22])[CH2:19][CH2:20]5)=[N:13][CH:14]=4)=[CH:31][C:32]3=[N:38][CH:37]=2)[CH:44]=[CH:43][CH:42]=1)=[O:47]

参加物

8

反応物 3

HCID 10340Sodium CarbonateHCID 16217947Tert-butyl 4-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)piperazine-1-carboxylateHCID 67980172N-[3-(7-chloroimidazo[1,2-b]pyridazin-3-yl)phenyl]-N'-(2,2,2-trifluoroethyl)urea

生成物 1

HCID 67980015Tert-butyl 4-(5-{3-[3-({[(2,2,2-trifluoroethyl)amino]carbonyl}amino)phenyl]imidazo[1,2-b]pyridazin-7-yl}pyridin-2-yl)piperazine-1-carboxylate

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
110 °C

実験手順

A mixture of tert-butyl 4-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]piperazine-1-carboxylate (46.3 mg, 0.119 mmol, Aldrich, Cat. No. 654337), N-[3-(7-chloroimidazo[1,2-b]pyridazin-3-yl)phenyl]-N′-(2,2,2-trifluoroethyl)urea (40.0 mg, 0.108 mmol, Example 30, Step 3), tetrakis(triphenylphosphine)palladium(0) (6.25 mg, 0.00541 mmol) and sodium carbonate (34.4 mg, 0.324 mmol) in dioxane (1 mL) and water (0.3 mL) was degassed and recharged with nitrogen three times, and heated and stirred at 110° C. for 3 h. 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 the desired product which was directly used in next step without further purification. LCMS (M+H)+: m/z=597.2.

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. customwas directly used in next step without further purification

出典と根拠

ORDレコード
ord-8f748affe5f842d79403bb7367bc440c
出典データセット
uspto-grants-2014_06
特許番号
US08754114B2

反応ノート

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