Guanidine Hydrochloride → HCID 11133737, compound

HRID 1871089Notes

Reaction equation

HRID 1871089 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:18]([C:19](=O)[CH3:20])=[C:17]([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=3)[N:16]=[CH:15]2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.COC(OC)N(C)C.NC(N)=N.Cl.C[O-].[Na+].[CH3:45][NH:46][C:47]([NH2:49])=[NH:48].Cl>CCO.O>[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:18]([C:19]3[CH:20]=[CH:45][N:46]=[C:47]([NH2:49])[N:48]=3)=[C:17]([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=3)[N:16]=[CH:15]2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 5742Guanidine HydrochlorideHCID 78373Dimethylformamide dimethyl acetal2×HCID 10199599HCID 10199599, compoundHCID 10942334Sodium Methoxide2×HCID 178485118HCID 178485118, compound

Product 1

HCID 11133737HCID 11133737, compoundYield 47%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of the ketoimidazole prepared in Example 13 above (0.38 g, 1.01 mmol) in 5 mL of EtOH was added N,N-dimethylformamide dimethyl acetal (0.4 mL, 0.36 g, 3.02 mmol) and then solution was heated at 90° C. for 3 h. After 3 h, an additional 1 mL of DMFDMA was added and heated for 3 h. At this time, TLC indicated no starting material and the solution was cooled to 70° C. and guanidine·HCl (0.19 g, 2.02 mmol) and NaOMe (25% w/w solution, 0.46 mL, 0.44 g, 2.02 mmol) were added. After 15 hours, additional N-methylguanidine·HCl (0.19 g, 2.02 mmol) and NaOMe (25% w/w solution, 0.46 mL, 0.44 g, 2.02 mmol) were added and heated at 75° C. for 24 h. The solution was cooled to room temperature, diluted with 50 mL of water and extracted 2×50 mL of EtOAC. The combined organics were concentrated and the residue was recrystallized from EtOAc to give 0.2 g (47%) of the title compound. 1H NMR (CDCl3) δ 8.19 (1H, d, J=5.2 Hz), 7.76 (1H, s), 7.44 (2H, m), 7.33 (5H, m), 7.01 (2H, t, J=8.6 Hz), 6.50 (1H, d, J=5.2 Hz), 5.17 (2H, br s), 4.54 (1H, m), 3.53 (2H, s), 3.02 (2H, m), 2.09 (6H, m).

Workup

  1. temperatureheated for 3 h
  2. temperaturethe solution was cooled to 70° C.
  3. waitAfter 15 hours
  4. temperatureheated at 75° C. for 24 h
  5. temperatureThe solution was cooled to room temperature
  6. extractionextracted 2×50 mL of EtOAC
  7. concentrationThe combined organics were concentrated
  8. customthe residue was recrystallized from EtOAc

Sources & evidence

ORD record
ord-82ced0542494469bbcee967bc29cc9ec
Source dataset
uspto-grants-2000_08
Patent number
US06100399

Reaction notes

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