Guanidine Hydrochloride → 2-(2-Amino-6-methyl-pyrimidin-4-yl)-pyrrolidine-1-carboxylic acid benzyl ester

HRID 1170472Notes

Reaction equation

HRID 1170472 reaction equation
[Na].Cl.[NH2:3][C:4]([NH2:6])=[NH:5].[CH2:7]([O:14][C:15]([N:17]1[CH2:21][CH2:20][CH2:19][CH:18]1[C:22](=O)[CH2:23][C:24](=O)[CH3:25])=[O:16])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>C(O)C>[CH2:7]([O:14][C:15]([N:17]1[CH2:21][CH2:20][CH2:19][CH:18]1[C:22]1[CH:23]=[C:24]([CH3:25])[N:3]=[C:4]([NH2:6])[N:5]=1)=[O:16])[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

Participants

5

Reactant 3

HCID 5742Guanidine HydrochlorideHCID 5360545Sodium2×HCID 167502742-(3-Oxo-butyryl)-pyrrolidine-1-carboxylic acid benzyl ester

Product 1

HCID 167502752-(2-Amino-6-methyl-pyrimidin-4-yl)-pyrrolidine-1-carboxylic acid benzyl esterYield 46%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

Sodium (550 mg, 25.0 mmol) was added portionwise to a stirred solution of anhydrous ethanol (30 mL) under nitrogen at room temperature. When all the sodium had dissolved, to the solution was added a solution of guanidine hydrochloride (2.28 g, 25.0 mmol) in ethanol (20 mL). The resulting mixture was stirred for 20 minutes. The precipitated sodium chloride was removed by filtration and to the clear filtrate was added 2-(3-oxo-butyryl)-pyrrolidine-1-carboxylic acid benzyl ester (6.87 g, 23.7 mmol). The flask was then fitted with a Dean-Stark Tube and 20 mL of distillate was removed as the solution was heated to reflux under nitrogen for 12 h. The mixture was allowed to cool to room temperature, then was gradually cooled to −5° C. The resulting solid was collected by filtration and air dried to give 3.37 g (46%) of 2-(2-amino-6-methyl-pyrimidin-4-yl)-pyrrolidine-1-carboxylic acid benzyl ester as cream colored crystals. [M+H]+ 312.88.

Workup

  1. customThe precipitated sodium chloride was removed by filtration and to the clear filtrate
  2. customThe flask was then fitted with a Dean-Stark Tube and 20 mL of distillate
  3. customwas removed as the solution
  4. temperaturewas heated
  5. temperatureto reflux under nitrogen for 12 h
  6. temperaturewas gradually cooled to −5° C
  7. filtrationThe resulting solid was collected by filtration and air
  8. customdried

Sources & evidence

ORD record
ord-ce1fe79b4c374cc39b8b154091542fb1
Source dataset
uspto-grants-2010_11
Patent number
US07825256B2

Reaction notes

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