Pyridine → HCID 73505857, compound

HRID 590878Notes

Reaction equation

HRID 590878 reaction equation
[NH2:1][C:2]1[C:6]2[C:7]([CH3:23])=[N:8][C:9]([NH:11][C:12]([NH:14][C@@H:15]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH3:16])=[O:13])=[CH:10][C:5]=2[NH:4][N:3]=1.N1C=CC=CC=1.[C:30](OC(=O)C)(=[O:32])[CH3:31].C(Cl)(=O)C.[OH-].[Na+]>C(#N)C.O.ClCCl.O1CCCC1>[CH3:23][C:7]1[C:6]2[C:2]([NH:1][C:30](=[O:32])[CH3:31])=[N:3][NH:4][C:5]=2[CH:10]=[C:9]([NH:11][C:12]([NH:14][C@@H:15]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH3:16])=[O:13])[N:8]=1

Participants

9

Reactant 5

HCID 1049PyridineHCID 6367Acetyl chlorideHCID 7918Acetic AnhydrideHCID 14798Sodium HydroxideHCID 73505856HCID 73505856, compound

Product 1

HCID 73505857HCID 73505857, compound

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Conditions

Temperature
50 °C

Procedure

A conical reaction vial was charged with (R)-1-(3-amino-4-methyl-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea (101 mg, 0.325 mmol) and tetrahydrofuran (3000 μl) was injected. To the resulting solution was added pyridine (132 μl, 1.627 mmol) and acetic anhydride (95 μl, 1.009 mmol). The reaction was stirred for 1 hour and no conversion was observed. Acetyl chloride (116 μl, 1.627 mmol) was injected and the reaction became heterogenous. Dichloromethane (3 mL) was added to give a homogenous reaction solution. The reaction was stirred at ambient temperature for 30 minutes. Solvent was removed on the rotovap. Dioxane (3 ml) was added followed by 1N sodium hydroxide (0.256 ml, 0.256 mmol) and the reaction was heated to 50° C. for 30 minutes. Reversed phase HPLC was performed directly on the crude reaction mixture (5-40% ACN/Water, 30 mm Focus Gradient). The active fractions were frozen and concentrated on the lyophilizer, the residue was dissolved in methanol filtered through immobilized bicarbonate and the filtrate was concentrated to give the title compound. MS ESI calc'd for C18H20N6O2. [M+H]+ 353. found 353. 1H NMR (ppm, 500 Mhz, DMSO-d6): δ 12.72 (s, 1H), 10.01 (s, 1H), 9.26-8.75 (m, 1H), 8.00 (s, 1H), 7.69-7.13 (m, 6H), 5.09-4.69 (m, 1H), 3.31 (s, 3H), 2.06 (s, 3H), 1.39 (d, J=6.9 Hz, 1H).

Workup

  1. customA conical reaction
  2. customto give a homogenous reaction solution
  3. stirringThe reaction was stirred at ambient temperature for 30 minutes
  4. customSolvent was removed on the rotovap
  5. additionDioxane (3 ml) was added
  6. temperatureThe active fractions were frozen
  7. concentrationconcentrated on the lyophilizer
  8. dissolutionthe residue was dissolved in methanol
  9. filtrationfiltered through immobilized bicarbonate
  10. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-36b4121da74d4b56889056521bfb7336
Source dataset
uspto-grants-2016_01
Patent number
US09233979B2

Reaction notes

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