Sodium Iodide → 1-bromo-3-(4-methoxybenzyl)-7-phenethylpyrazolo[3,4-b]pyrrolo[3,4-d]pyridine-6,8(3H,7H)-dione

HRID 1400112Notes

Reaction equation

HRID 1400112 reaction equation
[Br:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[C:8]3[C:13](=[O:14])[N:12]([CH2:15][CH2:16][C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)[C:11](=[O:23])[C:9]3=2)[NH:4][N:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[I-].[Na+].[CH3:32][O:33][C:34]1[CH:41]=[CH:40][C:37]([CH2:38]Cl)=[CH:36][CH:35]=1>CN(C)C=O>[Br:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[C:8]3[C:13](=[O:14])[N:12]([CH2:15][CH2:16][C:17]4[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=4)[C:11](=[O:23])[C:9]3=2)[N:4]([CH2:38][C:37]2[CH:40]=[CH:41][C:34]([O:33][CH3:32])=[CH:35][CH:36]=2)[N:3]=1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 10796Cesium carbonateHCID 699934-Methyloxybenzyl chlorideHCID 178515168HCID 178515168, compound

Product 1

HCID 595071011-bromo-3-(4-methoxybenzyl)-7-phenethylpyrazolo[3,4-b]pyrrolo[3,4-d]pyridine-6,8(3H,7H)-dioneYield 60.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-bromo-7-phenethylpyrazolo[3,4-b]pyrrolo[3,4-d]pyridine-6,8(3H,7H)-dione (500 mg, 1.34 mmol) in anhydrous N,N-dimethylformamide (5 ml), cesium carbonate (2.19 g, 6.7 mmol) and sodium iodide (27 mg, 0.2 mmol) were added followed p-methoxybenzyl chloride (0.18 mL, 2 mmol). The reaction mixture was stirred at room temperature for 2 hours. After completion of reaction (TLC and LCMS), the reaction mixture was poured over ice and extracted with ethyl acetate (3×50 ml). The combined organic layer was dried over sodium sulfate and evaporated under reduced pressure to give a residue which was purified by column chromatography on silica gel using a gradient of 0-20% ethyl acetate-hexanes to afford 1-bromo-3-(4-methoxybenzyl)-7-phenethylpyrazolo[3,4-b]pyrrolo[3,4-d]pyridine-6,8(3H,7H)-dione (400 mg, 60%) as a solid. 1H NMR (400 MHz, CDCl3): δ 9.00 (s, 1H), 7.35 (d, 2H), 7.20-7.30 (m, 5H), 6.80 (d, 2H), 5.70 (s, 2H), 3.95 (t, 2H), 3.80 (s, 3H), 3.00 (t, 2H); LCMS: [M+H] 491.

Workup

  1. customAfter completion of reaction (TLC and LCMS)
  2. additionthe reaction mixture was poured over ice
  3. extractionextracted with ethyl acetate (3×50 ml)
  4. dry with materialThe combined organic layer was dried over sodium sulfate
  5. customevaporated under reduced pressure
  6. customto give a residue which
  7. customwas purified by column chromatography on silica gel using a gradient of 0-20% ethyl acetate-hexanes

Sources & evidence

ORD record
ord-d527688439044ac7b88fbd406bb2cf35
Source dataset
uspto-grants-2014_12
Patent number
US08906928B2

Reaction notes

Loading…