Methyl iodide → 4,6-dichloro-3-methoxy-1-trityl-1H-pyrazolo[4,3-c]pyridine

HRID 588134Notes

Reaction equation

HRID 588134 reaction equation
[Cl:1][C:2]1[C:7]2[C:8](=[O:11])[NH:9][NH:10][C:6]=2[CH:5]=[C:4]([Cl:12])[N:3]=1.Cl[C:14]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[H-].[Na+].[C:35](=O)([O-])[O-].[K+].[K+].IC>CN(C=O)C.O>[Cl:1][C:2]1[C:7]2[C:8]([O:11][CH3:35])=[N:9][N:10]([C:14]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:6]=2[CH:5]=[C:4]([Cl:12])[N:3]=1

Participants

8

Reactant 5

HCID 6328Methyl iodideHCID 6456Trityl chlorideHCID 11430Potassium CarbonateHCID 24758Sodium hydrideHCID 1182717174,6-dichloro-1H-pyrazolo[4,3-c]pyridin-3(2H)-one

Product 1

HCID 1182725104,6-dichloro-3-methoxy-1-trityl-1H-pyrazolo[4,3-c]pyridineYield 62.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

4,6-dichloro-1H-pyrazolo[4,3-c]pyridin-3(2H)-one (1160 mg, 5.69 mmol) was dissolved in DMF (20 ml), charged with (chloromethanetriyl)tribenzene (1744 mg, 6.25 mmol) followed by sodium hydride (341 mg, 8.53 mmol) and allowed to stir at rt for 1 h. The tritylation was complete by LC/MS. The reaction was charged with potassium carbonate (1572 mg, 11.37 mmol) followed by iodomethane (0.533 ml, 8.53 mmol) and allowed to stir overnight at rt. The alkylation was complete by LC/MS. The reaction was charged with 40 mL water, cooled to 0° C. and the precipitate was filtered and washed 2×20 mL water. The yellow solid was dissolved in 20 mL DCM and poured onto a 100 g Biotage SNAP column and purified 5-25% EtOAc/hexanes to provide 4,6-dichloro-3-methoxy-1-trityl-1H-pyrazolo[4,3-c]pyridine (37B, 1.64 g, 3.56 mmol, 62.7% yield) as a white solid. MS: [M+H]+ m/z 460.

Workup

  1. stirringto stir overnight at rt
  2. temperaturecooled to 0° C.
  3. filtrationthe precipitate was filtered
  4. washwashed 2×20 mL water
  5. dissolutionThe yellow solid was dissolved in 20 mL DCM
  6. additionpoured onto a 100 g Biotage SNAP column
  7. custompurified 5-25% EtOAc/hexanes

Sources & evidence

ORD record
ord-f4c8c9ba95ca4617b6f2d1fe5a3debca
Source dataset
uspto-grants-2016_01
Patent number
US09226922B2

Reaction notes

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