Dimethylformamide → 7-Iodo-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-b]pyridine

HRID 1522597Notes

Reaction equation

HRID 1522597 reaction equation
[I:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[N:9][NH:10][C:3]=12.[H-].[Na+].CN(C=O)C.Cl[CH2:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=1>[Cl-].[NH4+]>[I:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[N:9][N:10]([CH2:19][C:20]3[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=3)[C:3]=12.[I:1][C:2]1[C:3]2[C:4](=[CH:8][N:9]([CH2:19][C:20]3[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=3)[N:10]=2)[N:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 699934-Methyloxybenzyl chlorideHCID 674695597-iodo-1H-pyrazolo[4,3-b]pyridine

Product 2

HCID 674695617-Iodo-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-b]pyridineHCID 674704207-iodo-1-(4-methoxybenzyl)-1H-pyrazolo[4,3-b]pyridine

Reagents, catalysts & solvents 1

HCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
0 °C

Procedure

7-Iodo-1H-pyrazolo[4,3-b]pyridine (0.75 g, 3.06 mmol) and sodium hydride were combined in DMF (30.6 mL) (0.147 g, 3.67 mmol) and stirred for 10 minutes then cooled to 0° C. 1-(Chloromethyl)-4-methoxybenzene (0.438 ml, 3.21 mmol) was added and the reaction was stirred at 0° C. for 15 minutes and then warmed to room temperature over 2 hours. Ice water (200 mL) and saturated ammonium chloride solution (50 mL) was added and the mixture was extracted with ethyl acetate (75 mL×2). The organics were combined, dried over sodium sulfate, and concentrated to dark oil. The oil was dissolved in a mixture of ethyl acetate, methanol and dichloromethane and loaded onto a silica chromatography column which was eluted using 40% ethyl acetate in hexanes to give 7-iodo-1-(4-methoxybenzyl)-1H-pyrazolo[4,3-b]pyridine and 7-iodo-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-b]pyridine as a dark yellow film (1 g) which was used immediately. MS [M+H] found 366.2.

Workup

  1. stirringthe reaction was stirred at 0° C. for 15 minutes
  2. temperaturewarmed to room temperature over 2 hours
  3. extractionthe mixture was extracted with ethyl acetate (75 mL×2)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated to dark oil
  6. dissolutionThe oil was dissolved in a mixture of ethyl acetate, methanol and dichloromethane
  7. washwas eluted

Sources & evidence

ORD record
ord-a54f45201cff48f9b066555fa0f6b460
Source dataset
uspto-grants-2015_07
Patent number
US09073918B2

Reaction notes

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