Diisopropylethylamine → 4-(4-((2-Fluoroethoxy)methyl)phenyl)piperazine-1-carboximidamide

HRID 452302Notes

Reaction equation

HRID 452302 reaction equation
Cl.[F:2][CH2:3][CH2:4][O:5][CH2:6][C:7]1[CH:12]=[CH:11][C:10]([N:13]2[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]2)=[CH:9][CH:8]=1.C(N(C(C)C)CC)(C)C.Cl.[N:29]1([C:34](=N)[NH2:35])C=CC=N1>CN(C=O)C>[F:2][CH2:3][CH2:4][O:5][CH2:6][C:7]1[CH:8]=[CH:9][C:10]([N:13]2[CH2:14][CH2:15][N:16]([C:34](=[NH:29])[NH2:35])[CH2:17][CH2:18]2)=[CH:11][CH:12]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 2734672Pyrazole-1-carboxamidine monohydrochlorideHCID 866449591-(4-((2-Fluoroethoxy)methyl)-phenyl)piperazine hydrochloride

Product 1

HCID 594705384-(4-((2-Fluoroethoxy)methyl)phenyl)piperazine-1-carboximidamideYield 41%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(4((2-fluoroethoxy)methyl)-phenyl)piperazine hydrochloride (50 mg, 0.12 mmol) and diisopropylethylamine (67 μL, 0.38 mmol) in DMF (1 mL) was added 1H-pyrazole-1-carboximidamide hydrochloride (29 mg, 0.20 mmol). The reaction stirred at room temperature for 24 h. The next day, the reaction mixture was concentrated to yield a crude oil, which was purified via HPLC using a Phenomenex Luna C-18 (2) column (10μ, 250×21.2 mm, gradient method 15-55% B over 20 min., where B=90% ACN in water using 0.1% formic acid as a modifier and A=water using 0.1% formic acid as a modifier) with a flow rate of 20 mL/min afforded 4-(4-((2-fluoroethoxy)methyl)phenyl)piperazine-1-carboximidamide as a white solid (20 mg, 41% yield based on recovered starting material). 1H NMR (300 MHz, DMSO-d6): δ 7.58 (br s, 4H), 7.211 (d, 2H, J=8.5 Hz), 6.96 (d, 2H, J=8.6 Hz), 4.61 (m, 1H), 4.45 (m, 1H), 4.41 (s, 2H), 3.67 (m, 1H), 3.58 (dd, 4H, J=4.2, 3.9 Hz), 3.22 (m, 5H); 19F NMR (282.4 MHz, DMSO-d6): δ−221.39 (m, 1F); 13C NMR (75.5 MHz, DMSO-d6): δ 156.1, 149.8, 128.9, 115.4, 84.1 (81.9), 71.8, 68.6 (68.4), 47.5, 44.7; HRMS calcd for C14H21FN4O: 281.177216 found 281.17720.

Workup

  1. concentrationThe next day, the reaction mixture was concentrated
  2. customto yield a crude oil, which
  3. customwas purified via HPLC
  4. customover 20 min.
  5. customwhere B=90% ACN in water using 0.1% formic acid as a modifier and A=water using 0.1% formic acid as a modifier) with a flow rate of 20 mL/min afforded
  6. custom4-(4-((2-fluoroethoxy)methyl)phenyl)piperazine-1-carboximidamide as a white solid (20 mg, 41% yield based on recovered starting material)

Sources & evidence

ORD record
ord-26c3293f86d84414bcfdc88bdc888644
Source dataset
uspto-grants-2013_07
Patent number
US08491868B2

Reaction notes

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