Clonidine → 1-Isonicotinoyl-2-(2',6'-dichlorophenylamino)-2-imidazoline

HRID 2166823Notes

Reaction equation

HRID 2166823 reaction equation
[C:1]([OH:9])(=O)[C:2]1[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=1.[Cl:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([Cl:17])[C:12]=1[NH:18][C:19]1[NH:20][CH2:21][CH2:22][N:23]=1>O1CCCC1>[C:1]([N:23]1[CH2:22][CH2:21][N:20]=[C:19]1[NH:18][C:12]1[C:13]([Cl:17])=[CH:14][CH:15]=[CH:16][C:11]=1[Cl:10])(=[O:9])[C:2]1[CH:3]=[CH:4][N:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 2803ClonidineHCID 5922Isonicotinic Acid

Product 1

HCID 127839071-Isonicotinoyl-2-(2',6'-dichlorophenylamino)-2-imidazolineYield 42.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

2.7 g (21.0 millimoles) of isonicotinic acid are added to 800 ml of absolute tetrahydrofuran, 4.2 g (25.9 millimoles) of N,N'-carbonyl-diimidazole are introduced and the mixture is refluxed for 2 hours. When it has cooled, a solution of 5.0 g (21.7 millimoles) of 2-(2',6'-dichlorophenylamino)-2-imidazoline in 100 ml of absolute tetrahydrofuran is added and the batch is stirred for 50 hours at room temperature. It is then freed from solvent on a rotary evaporator, the oily residue is taken up in 500 ml of tetrahydrofuran and the solution is added dropwise, with stirring, to 1.5 liters of 0.1% strength sodium bicarbonate solution. The crystals obtained (6.5 g) are recrystallized once from a 100:140 isopropanol/petroleum ether mixture and once from pure isopropanol. 3.0 g of pure 1-isonicotinoyl-2-(2',6'-dichlorophenylamino)-2-imidazoline are obtained, melting point 82.5°-83.5° C. (the product contains 0.5 mole of isopropanol of crystallization).

Workup

  1. additionare introduced
  2. temperaturethe mixture is refluxed for 2 hours
  3. temperatureWhen it has cooled
  4. customIt is then freed from solvent on a rotary evaporator
  5. additionthe solution is added dropwise
  6. stirringwith stirring, to 1.5 liters of 0.1% strength sodium bicarbonate solution
  7. customThe crystals obtained (6.5 g)
  8. customare recrystallized once from a 100:140 isopropanol/petroleum ether mixture and once from pure isopropanol

Sources & evidence

ORD record
ord-dd1a0639bb32458eb9d8f1a3d46e6b9e
Source dataset
uspto-grants-1983_06
Patent number
US04389403

Reaction notes

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