1-Piperazinecarboxylic acid, ethyl ester → 4-{5-[2-(2,2,6,6-Tetramethyl-piperidin-4-ylamino)-pyrimidin-4-yl]-thiophen-2-yl}-piperazine-1-carboxylic acid ethyl ester

HRID 1434949ノート

反応式

HRID 1434949 の反応式
Br[C:2]1[S:6][C:5]([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][CH:14]3[CH2:19][C:18]([CH3:21])([CH3:20])[NH:17][C:16]([CH3:23])([CH3:22])[CH2:15]3)[N:8]=2)=[CH:4][CH:3]=1.CC([O-])(C)C.[Na+].[CH2:30]([O:32][C:33]([N:35]1[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]1)=[O:34])[CH3:31]>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:30]([O:32][C:33]([N:35]1[CH2:36][CH2:37][N:38]([C:2]2[S:6][C:5]([C:7]3[CH:12]=[CH:11][N:10]=[C:9]([NH:13][CH:14]4[CH2:19][C:18]([CH3:21])([CH3:20])[NH:17][C:16]([CH3:23])([CH3:22])[CH2:15]4)[N:8]=3)=[CH:4][CH:3]=2)[CH2:39][CH2:40]1)=[O:34])[CH3:31]

参加物

6

反応物 3

HCID 84311-Piperazinecarboxylic acid, ethyl esterHCID 23676156Sodium t-butoxideHCID 57936128{4-[5-Bromothiophen-2-yl]-pyrimidin-2-yl}-(2,2,6,6-tetramethyl-piperidin-4-yl)-amine

生成物 1

HCID 113748694-{5-[2-(2,2,6,6-Tetramethyl-piperidin-4-ylamino)-pyrimidin-4-yl]-thiophen-2-yl}-piperazine-1-carboxylic acid ethyl ester

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 312751,4-Dioxane溶媒

実験手順

[4-(5-Bromo-thiophen-2-yl)-pyrimidin-2-yl]-(2,2,6,6-tetramethyl-piperidin-4-yl)-amine (Step C of Example 5, 198 mg, 0.5 mmol), NaOtBu (53 mg, 0.55 mmol), R-(+)-BINAP (6.2 mg, 0.01 mmol), Pd(OAc)2 (6.2 mg, 0.027 mol) and N-ethoxycarbonylpiperazine (158 mg, 1.0 mmol) were refluxed in 1,4-dioxan for 18 hours. The reaction mixture was poured on water and extracted three times with EtOAc. The combined organic phases were dried over sodium sulfate, filtered, and purified via chromatography on silicagel (TBME/MeOH/ammonia:98/1.8/0.2 to 95/4.5/0.5) to give the title compound as yellow solid. Yield: 120 mg (50%).

後処理

  1. additionThe reaction mixture was poured on water
  2. extractionextracted three times with EtOAc
  3. dry with materialThe combined organic phases were dried over sodium sulfate
  4. filtrationfiltered
  5. custompurified via chromatography on silicagel (TBME/MeOH/ammonia:98/1.8/0.2 to 95/4.5/0.5)

出典と根拠

ORDレコード
ord-4103368cd2954852b84ffa0b548fc911
出典データセット
uspto-grants-2009_11
特許番号
US07615562B2

反応ノート

読み込み中…