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 1434949Notes

Reaction equation

HRID 1434949 reaction equation
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]

Participants

6

Reactant 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

Product 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

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Procedure

[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%).

Workup

  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)

Sources & evidence

ORD record
ord-4103368cd2954852b84ffa0b548fc911
Source dataset
uspto-grants-2009_11
Patent number
US07615562B2

Reaction notes

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