Diisopropylethylamine → 4-Guanidinomethyl-benzoic acid methyl ester dihydrate

HRID 416225Notes

Reaction equation

HRID 416225 reaction equation
Cl.[NH2:2][CH2:3][C:4]1[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=1.Cl.[N:15]1([C:20](N)=[NH:21])C=CC=N1.CCN(C(C)C)C(C)C>C(O)C>[OH2:9].[OH2:9].[CH3:11][O:10][C:8](=[O:9])[C:7]1[CH:6]=[CH:5][C:4]([CH2:3][NH:2][C:20]([NH2:21])=[NH:15])=[CH:13][CH:12]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 2729253Methyl 4-(aminomethyl)benzoate hydrochlorideHCID 2734672Pyrazole-1-carboxamidine monohydrochloride

Product 1

HCID 1784979354-Guanidinomethyl-benzoic acid methyl ester dihydrateYield 233.8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of methyl 4-(aminomethyl)benzoate hydrochloride (5 g) in dry ethanol (25 mL) was added 1H-pyrazole-1-carboxamidine hydrochloride (4.4 g) followed by DIPEA (13.0 mL) and the mixture was refluxed for 3 h. Ethanol was removed under vacuum. To the remaining viscous oil saturated solution of NaHCO3 (50 mL) was slowly added under vigorous stirring followed by addition of 300 ml water (resultant pH 9). A white solid is formed and stirring was continued for 1 h. This material was filtered off, washed with water (200 mL) and tert-butyl methyl ether (50 mL), and dried to give the title compound 24 as a white powder (4.7 g, 91%). 1H NMR (400 MHz, DMSO-d6) δ (ppm): 7.91 (d, J=8.0 Hz, 2H), 7.39 (d, J=8.0 Hz, 2H), 4.39 (s, 2H), 3.83 (s, 3H), 3.80-2.80 [m, 4H+2H2O (determined by elemental analysis]).

Workup

  1. temperaturethe mixture was refluxed for 3 h
  2. customEthanol was removed under vacuum
  3. additionTo the remaining viscous oil saturated solution of NaHCO3 (50 mL) was slowly added
  4. additionfollowed by addition of 300 ml water (resultant pH 9)
  5. customA white solid is formed
  6. stirringstirring
  7. filtrationThis material was filtered off
  8. washwashed with water (200 mL) and tert-butyl methyl ether (50 mL)
  9. customdried

Sources & evidence

ORD record
ord-ef3faf379faf464c9611f50c51e31be0
Source dataset
uspto-grants-2012_01
Patent number
US08088805B2

Reaction notes

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