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 1434949노트

반응식

HRID 1434949 반응식
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]

참가 물질

6

반응물 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

생성물 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

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 312751,4-Dioxane용매

실험 절차

[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%).

후처리

  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)

출처 및 근거

ORD 기록
ord-4103368cd2954852b84ffa0b548fc911
출처 데이터셋
uspto-grants-2009_11
특허 번호
US07615562B2

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