1-Hydroxybenzotriazole → [4-(Pyrrolidin-1-yl)piperidin-1-yl][4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methanone

HRID 80548

Reaction equation

HRID 80548 reaction equation
[CH3:1][C:2]1([CH3:18])[C:6]([CH3:8])([CH3:7])[O:5][B:4]([C:9]2[CH:17]=[CH:16][C:12]([C:13]([OH:15])=O)=[CH:11][CH:10]=2)[O:3]1.[N:19]1([CH:24]2[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]2)[CH2:23][CH2:22][CH2:21][CH2:20]1.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>CN(C=O)C>[N:19]1([CH:24]2[CH2:29][CH2:28][N:27]([C:13]([C:12]3[CH:11]=[CH:10][C:9]([B:4]4[O:5][C:6]([CH3:7])([CH3:8])[C:2]([CH3:1])([CH3:18])[O:3]4)=[CH:17][CH:16]=3)=[O:15])[CH2:26][CH2:25]2)[CH2:23][CH2:22][CH2:21][CH2:20]1

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 787034-(1-Pyrrolidinyl)piperidineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27346214-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acid

Product 1

HCID 57886103[4-(Pyrrolidin-1-yl)piperidin-1-yl][4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methanoneYield 42%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 4-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)benzoic acid (9.80 mmol, 2.43 g), 4-(1-pyrrolidinyl)piperidine (10.77 mol, 1.66 g), 1-hydroxybenzotriazole (16.67 mmol, 2.25 g), and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (19.57 mmol, 3.75 g) in DMF (30 mL) was stirred overnight at 60° C. Upon removal of DMF on rotavap, the residue was taken into mixture of EtOAc and H2O. The combined organic layers from extraction were stirred with aq. 2N HCl for 20 min and the aqueous layer was purified by reverse phase prep-HPLC to furnish the desired boronic acid (1.24 g. 42%).

Workup

  1. customUpon removal of DMF on rotavap
  2. additionthe residue was taken into mixture of EtOAc and H2O
  3. extractionThe combined organic layers from extraction
  4. customthe aqueous layer was purified by reverse phase prep-HPLC

Sources & evidence

ORD record
ord-2b9a53560a5e4de0a9233069280129c6
Source dataset
uspto-grants-2014_09
Patent number
US08846664B2

Linked notes

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