Dimethylformamide → 1-(4-methoxybenzyl)-4-(5-chloro-2-methyl-4-nitrophenoxy)-3-iodo-1H-pyrazolo[3,4-b]pyridine

HRID 2241281Notes

Reaction equation

HRID 2241281 reaction equation
[Cl:1][C:2]1[C:3]([N+:20]([O-:22])=[O:21])=[CH:4][C:5]([CH3:19])=[C:6]([CH:18]=1)[O:7][C:8]1[CH:13]=[CH:12][N:11]=[C:10]2[NH:14][N:15]=[C:16]([I:17])[C:9]=12.CN(C=O)C.C([O-])([O-])=O.[K+].[K+].Cl[CH2:35][C:36]1[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][CH:37]=1>O>[CH3:43][O:42][C:39]1[CH:40]=[CH:41][C:36]([CH2:35][N:14]2[C:10]3=[N:11][CH:12]=[CH:13][C:8]([O:7][C:6]4[CH:18]=[C:2]([Cl:1])[C:3]([N+:20]([O-:22])=[O:21])=[CH:4][C:5]=4[CH3:19])=[C:9]3[C:16]([I:17])=[N:15]2)=[CH:37][CH:38]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 699934-Methyloxybenzyl chlorideHCID 178428765HCID 178428765, compound

Product 1

HCID 685150271-(4-methoxybenzyl)-4-(5-chloro-2-methyl-4-nitrophenoxy)-3-iodo-1H-pyrazolo[3,4-b]pyridine

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

4-(5-Chloro-2-methyl-4-nitrophenoxy)-3-iodo-1H-pyrazolo[3,4-b]pyridine (26.5 g, 61.5 mmol) was dissolved in stirring DMF (100 mL). K2CO3 (17.0 g, 123 mmol) and 1-(chloromethyl)-4-methoxybenzene (10.1 ml, 73.9 mmol) were added and the reaction mixture was stirred at ambient temperature under N2 for 18 hours. The mixture was diluted with water, and then the water was decanted. The gum washed a second time with water, and the water decanted. The residue was partitioned between EtOAc (250 mL) and brine (100 mL). The phases were separated, and the organic phase was dried (Na2SO4), filtered, and concentrated. The resulting solid was triturated with diethyl ether (100 mL), and the yellow powder (27.3 g, 80%) filtered. The product was a 9:1 mixture of pyrazole regioisomers as determined by 1H NMR: (400 MHz, CDCl3, major regioisomer reported) δ 8.43 (d, J=5 Hz, 1H), 7.95 (s, 1H), 7.38 (d, J=9 Hz, 2H), 7.19 (s, 1H), 6.84 (d, J=9 Hz, 2H), 6.35 (d, J=5 Hz, 1H), 5.64 (s, 2H), 3.77 (s, 3H), 2.36 (s, 3H).

Workup

  1. customthe water was decanted
  2. washThe gum washed a second time with water
  3. customthe water decanted
  4. customThe residue was partitioned between EtOAc (250 mL) and brine (100 mL)
  5. customThe phases were separated
  6. dry with materialthe organic phase was dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe resulting solid was triturated with diethyl ether (100 mL)
  10. filtrationthe yellow powder (27.3 g, 80%) filtered
  11. additiona 9:1 mixture of pyrazole regioisomers

Sources & evidence

ORD record
ord-238620b2ff0741a2bf4d81f16692261e
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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