Diisopropylethylamine → HCID 178512999, compound

HRID 2260574Notes

Reaction equation

HRID 2260574 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[NH:8][CH:9]=[CH:10][C:3]=12.C(N(C(C)C)CC)(C)C.[CH2:20]([O:27][C:28]([N:30]([CH2:44][C@H:45]1[CH2:50][CH2:49][C@H:48]([C:51](Cl)=[O:52])[CH2:47][CH2:46]1)[C:31]([NH:33]C(OCC1C=CC=CC=1)=O)=[NH:32])=[O:29])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C[O-].[Na+]>C(#N)C.CO>[NH:8]1[C:4]2=[N:5][CH:6]=[CH:7][C:2]([NH:1][C:51]([C@H:48]3[CH2:47][CH2:46][C@H:45]([CH2:44][N:30]([C:28]([O:27][CH2:20][C:21]4[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=4)=[O:29])[C:31]([NH2:33])=[NH:32])[CH2:50][CH2:49]3)=[O:52])=[C:3]2[CH:10]=[CH:9]1

Participants

7

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 6392491H-pyrrolo(2,3-b)pyridin-4-amineHCID 10942334Sodium MethoxideHCID 178512420HCID 178512420, compound2×

Product 1

HCID 178512999HCID 178512999, compoundYield 43.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of 4-amino-1H-pyrrolo[2,3-b]pyridine (2.46 g) dissolved in acetonitrile (100 ml) was added diisopropylethylamine (6.5 ml). The mixture was stirred at 40° C. Trans-4-(1,3-dibenzyloxycarbonylguanidinomethyl)cyclohexanecarboxylic chloride (19.86 g) was added to this solution and the mixture was stirred at 50° C. for 2 hours. Then, diisopropylethylamine (6 ml) and trans-4-(1,3-dibenzyloxycarbonylguanidinomethyl)cyclohexanecarboxylic chloride (15.03 g) were added thereto and the mixture was stirred at 50° C. for 2 hours. The solvent was distilled away under reduced pressure and the residue obtained was dissolved in methanol (100 ml). Sodium methoxide (1.05 g) was added to this solution and the mixture was stirred under ice-cooling for 1 hour and at room temperature for 1 hour. The solvent was distilled away under reduced pressure, chloroform (200 ml) was added thereto and the mixture was washed with water. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give 3.61 g of trans-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-4-(1-benzyloxycarbonylguanidinomethyl)cyclohexanecarboxamide, melting point 160°-162° C.

Workup

  1. stirringthe mixture was stirred at 50° C. for 2 hours
  2. stirringthe mixture was stirred at 50° C. for 2 hours
  3. distillationThe solvent was distilled away under reduced pressure
  4. customthe residue obtained
  5. stirringthe mixture was stirred under ice-
  6. temperaturecooling for 1 hour and at room temperature for 1 hour
  7. distillationThe solvent was distilled away under reduced pressure, chloroform (200 ml)
  8. additionwas added
  9. washthe mixture was washed with water
  10. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-e6e9800103b9479b859d67903c7ecd26
Source dataset
uspto-grants-1995_12
Patent number
US05478838

Reaction notes

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