Diisopropylethylamine → 4-(2-Amidino-1,2,3,4-tetrahydroisoquinolin-7-yloxymethyl)-1-(pyrimidin-4-yl)piperidine-4-carboxylic acid dihydrochloride

HRID 412538Notes

Reaction equation

HRID 412538 reaction equation
C([O:3][C:4]([C:6]1([CH2:18][O:19][C:20]2[CH:29]=[C:28]3[C:23]([CH2:24][CH2:25][NH:26][CH2:27]3)=[CH:22][CH:21]=2)[CH2:11][CH2:10][N:9]([C:12]2[CH:17]=[CH:16][N:15]=[CH:14][N:13]=2)[CH2:8][CH2:7]1)=[O:5])C.C(N(C(C)C)CC)(C)C.[ClH:39].[N:40]1([C:45](N)=[NH:46])C=CC=N1>CN(C)C=O>[ClH:39].[ClH:39].[C:45]([N:26]1[CH2:25][CH2:24][C:23]2[C:28](=[CH:29][C:20]([O:19][CH2:18][C:6]3([C:4]([OH:3])=[O:5])[CH2:7][CH2:8][N:9]([C:12]4[CH:17]=[CH:16][N:15]=[CH:14][N:13]=4)[CH2:10][CH2:11]3)=[CH:21][CH:22]=2)[CH2:27]1)(=[NH:40])[NH2:46]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 2734672Pyrazole-1-carboxamidine monohydrochlorideHCID 600641441-(Pyrimidin-4-yl)-4-(1,2,3,4-tetrahydroisoquinolin-7-yloxymethyl)piperidine-4-carboxylic acid ethyl ester

Product 1

HCID 114090734-(2-Amidino-1,2,3,4-tetrahydroisoquinolin-7-yloxymethyl)-1-(pyrimidin-4-yl)piperidine-4-carboxylic acid dihydrochlorideYield 16.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(pyrimidin-4-yl)-4-(1,2,3,4-tetrahydroisoquinolin-7-yloxymethyl)piperidine-4-carboxylic acid ethyl ester (260 mg) in dimethylformamide (1 ml) were added diisopropylethylamine (0.24 ml) and 1H-pyrazole-1-carboxamidine hydrochloride (200 mg), and the mixture was stirred at room temperature for 2 hours. After completion of the reaction, the solvent was evaporated and the obtained residue was separated by HPLC (0.05% aqueous trifluoroacetic acid:methanol=6:4-2:8). The obtained residue was refluxed with conc. hydrochloric acid for 2 hours. After completion of the reaction, the solvent was evaporated and the obtained residue was washed with diethyl ether and dried under reduced pressure to give the title compound (51 mg).

Workup

  1. customAfter completion of the reaction
  2. customthe solvent was evaporated
  3. customthe obtained residue was separated by HPLC (0.05% aqueous trifluoroacetic acid:methanol=6:4-2:8)
  4. temperatureThe obtained residue was refluxed with conc. hydrochloric acid for 2 hours
  5. customAfter completion of the reaction
  6. customthe solvent was evaporated
  7. washthe obtained residue was washed with diethyl ether
  8. customdried under reduced pressure

Sources & evidence

ORD record
ord-d1cb9b52d354405e98bca3581913ea67
Source dataset
uspto-grants-2003_05
Patent number
US06562828B1

Reaction notes

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