Maleimide → 3-(4-methoxybenzyl)pyrazolo[3,4-b]pyrrolo[3,4-d]pyridine-6,8(3H,7H)-dione

HRID 1400106Notes

Reaction equation

HRID 1400106 reaction equation
Cl.[CH3:2][O:3][C:4]1[CH:16]=[CH:15][C:7]([CH2:8][N:9]2[C:13]([NH2:14])=[CH:12][CH:11]=[N:10]2)=[CH:6][CH:5]=1.[C:17](=O)([O-])[O-].[K+].[K+].COC(OC)N(C)C.[C:31]1(=[O:37])[NH:35][C:34](=[O:36])[CH:33]=[CH:32]1>O.C(O)(=O)C>[CH3:2][O:3][C:4]1[CH:5]=[CH:6][C:7]([CH2:8][N:9]2[C:13]3=[N:14][CH:17]=[C:33]4[C:34](=[O:36])[NH:35][C:31](=[O:37])[C:32]4=[C:12]3[CH:11]=[N:10]2)=[CH:15][CH:16]=1

Participants

7

Reactant 4

HCID 10935MaleimideHCID 11430Potassium CarbonateHCID 78373Dimethylformamide dimethyl acetalHCID 429375131-(4-methoxybenzyl)-1H-pyrazol-5-amine hydrochloride

Product 1

HCID 595071793-(4-methoxybenzyl)pyrazolo[3,4-b]pyrrolo[3,4-d]pyridine-6,8(3H,7H)-dioneYield 23%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

1-(4-methoxybenzyl)-1H-pyrazol-5-amine hydrochloride (2.0 g, 8.35 mmol) was free-based with 10% aqueous potassium carbonate (100 ml) and extracted with diethyl ether (100 ml). The organic layer was concentrated under reduced pressure to afford a yellow solid. N,N-dimethylformamide dimethylacetal (15 ml) was added and the mixture heated to 120° C. for 2.5 hours. The mixture was concentrated under reduced pressure which was then treated with maleimide (1.62 g, 16.7 mmol) and acetic acid (10 ml) and heated to 50° C. for 2 days. The mixture was poured into cold water (250 ml) and extracted with ethyl acetate (3×100 ml). The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to afford 3-(4-methoxybenzyl)pyrazolo[3,4-b]pyrrolo[3,4-d]pyridine-6,8(3H,7H)-dione as a pale yellow solid (593 mg, 23%). M.p.=196-197° C.; 400 MHz 1H NMR (DMSO-d6) δ: 11.55 (s, 1H), 9.02 (s, 1H), 8.50 (s, 1H), 7.24 (d, J=8.8 Hz, 2H), 6.85 (d, J=8.8 Hz, 2H), 5.70 (s, 2H), 3.68 (s, 3H); LCMS: 309 [M+H]. 1-(4-methoxybenzyl)-1H-pyrazol-5-amine hydrochloride was made according to the procedure described in Bioorganic and Medicinal Chemistry Letters, vol. 13, pp. 1133-6 (2003).

Workup

  1. extractionextracted with diethyl ether (100 ml)
  2. concentrationThe organic layer was concentrated under reduced pressure
  3. customto afford a yellow solid
  4. concentrationThe mixture was concentrated under reduced pressure which
  5. temperatureheated to 50° C. for 2 days
  6. extractionextracted with ethyl acetate (3×100 ml)
  7. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-291ee326e9dc46558cedab2713452bfc
Source dataset
uspto-grants-2014_12
Patent number
US08906928B2

Reaction notes

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