Triethylamine → N-(4-(4-hydroxypiperidin-1-yl)-phenyl)-4-((1-methylpyrrol-2-yl)-carbonyl)-1-piperazinecarboxamide

HRID 2174691Notes

Reaction equation

HRID 2174691 reaction equation
Cl[C:2](OC1C=CC([N+]([O-])=O)=CC=1)=[O:3].[OH:14][CH:15]1[CH2:20][CH2:19][N:18]([C:21]2[CH:26]=[CH:25][C:24]([NH2:27])=[CH:23][CH:22]=2)[CH2:17][CH2:16]1.Cl.[CH3:29][N:30]1[CH:34]=[CH:33][CH:32]=[C:31]1[C:35]([N:37]1[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1)=[O:36].C(N(CC)CC)C.C(=O)(O)[O-].[Na+]>O1CCCC1>[OH:14][CH:15]1[CH2:20][CH2:19][N:18]([C:21]2[CH:26]=[CH:25][C:24]([NH:27][C:2]([N:40]3[CH2:39][CH2:38][N:37]([C:35]([C:31]4[N:30]([CH3:29])[CH:34]=[CH:33][CH:32]=4)=[O:36])[CH2:42][CH2:41]3)=[O:3])=[CH:23][CH:22]=2)[CH2:17][CH2:16]1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 821294-Nitrophenyl chloroformateHCID 516892Sodium BicarbonateHCID 167921071-(4-Aminophenyl)piperidin-4-olHCID 665843721-(1-methyl-1H-pyrrole-2-carbonyl)piperazine hydrochloride

Product 1

HCID 46911245N-(4-(4-hydroxypiperidin-1-yl)-phenyl)-4-((1-methylpyrrol-2-yl)-carbonyl)-1-piperazinecarboxamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

4-nitrophenyl chloroformate (242 mg, 1.2 mmol) was dissolved in tetrahydrofuran (3 ml), and a tetrahydrofuran (4 ml) solution of the 4-hydroxy-N-(4-aminophenyl)piperidine (211 mg, 1.0 mmol) obtained in Example 1(2) was added dropwise at −30° C. After stirring for 30 minutes at the same temperature, 1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]piperazine hydrochloride (252 mg, 1.1 mmol) and triethylamine (0.49 ml, 3.5 mmol) were added to the mixture, followed by stirring at room temperature for 17 hours. A saturated sodium bicarbonate aqueous solution was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with water and saturated sodium chloride, and dried over anhydrous sodium sulfate. After the desiccant was filtered off, the residue obtained by evaporation under reduced pressure was purified using medium pressure silica gel flash column chromatography (NH silica gel, methanol:chloroform=0:1 to 1:50), thereby obtaining N-(4-(4-hydroxypiperidin-1-yl)-phenyl)-4-((1-methylpyrrol-2-yl)-carbonyl)-1-piperazinecarboxamide (256 mg, 62%) as a milky-white solid.

Workup

  1. additionwere added to the mixture
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe organic layer was washed with water and saturated sodium chloride
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationAfter the desiccant was filtered off
  6. customthe residue obtained by evaporation under reduced pressure
  7. customwas purified

Sources & evidence

ORD record
ord-03bf2b0db63447eca0aaaa4fa33b64a8
Source dataset
uspto-grants-2015_06
Patent number
US09062035B2

Reaction notes

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