Methyl iodide → 4-(4-chlorophenyl)-2,3-dimethyl-5-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-4,5-dihydropyrrolo-[3,4-c]pyrazol-6(2H)-one

HRID 873797Notes

Reaction equation

HRID 873797 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:15]3[C:11](=[N:12][NH:13][C:14]=3[CH3:16])[C:10](=[O:17])[N:9]2[C:18]2[CH:23]=[CH:22][C:21](=[O:24])[N:20]([CH3:25])[CH:19]=2)=[CH:4][CH:3]=1.[H-].[Na+].[CH3:28]I>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:15]3[C:11](=[N:12][N:13]([CH3:28])[C:14]=3[CH3:16])[C:10](=[O:17])[N:9]2[C:18]2[CH:23]=[CH:22][C:21](=[O:24])[N:20]([CH3:25])[CH:19]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 1177026284-(4-chlorophenyl)-3-methyl-5-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-4,5-dihydropyrrolo-[3,4-c]pyrazol-6(2H)-one

Product 1

HCID 918263004-(4-chlorophenyl)-2,3-dimethyl-5-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-4,5-dihydropyrrolo-[3,4-c]pyrazol-6(2H)-oneYield 38.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 4-(4-chlorophenyl)-3-methyl-5-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-4,5-dihydropyrrolo[3,4-c]pyrazol-6(2H)-one (Example 2) (25 mg, 0.070 mmol) in DMF (1 mL) under Ar was added NaH (3.38 mg, 0.085 mmol). The reaction mixture was stirred at rt for 30 min and MeI (6.61 μL, 0.106 mmol) was added. After 1 hr at rt, the reaction mixture was quenched with a saturated aq. NaHCO3 solution and extracted with EtOAc. The combined organic layers were washed with a saturated aq. NaHCO3 solution, dried over Na2SO4, and evaporated. The crude material was purified by preparative HPLC (Gilson gx-281; column: Sunfire C18, 30×100 mm, 5 μm; flow: 30 mL/min; gradient: 5% to 100% B in 20 min; A=0.1% TFA in H2O, B=CH3CN; detection: UV) to afford the title product (10 mg, 0.027 mmol, 38% yield). tR: 3.39 min (HPLC 1); tR: 0.74 min (LC-MS 2); ESI-MS: 369 [M+H]+ (LC-MS 2); 1H NMR (400 MHz, DMSO-d6) δ ppm 2.05 (s, 3H) 3.34 (s, 3H) 3.83 (s, 3H) 6.10 (s, 1H) 6.30 (d, J=9.8 Hz, 1H) 7.23 (d, J=8.6 Hz, 2H) 7.35 (d, J=8.6 Hz, 2H) 7.44 (dd, J=9.8, 2.7 Hz, 1H) 7.89 (d, J=2.7 Hz, 1H). In addition to the title compound, a second product was isolated during this purification process and is described in Example 4.

Workup

  1. waitAfter 1 hr at rt
  2. customthe reaction mixture was quenched with a saturated aq. NaHCO3 solution
  3. extractionextracted with EtOAc
  4. washThe combined organic layers were washed with a saturated aq. NaHCO3 solution
  5. dry with materialdried over Na2SO4
  6. customevaporated
  7. customThe crude material was purified by preparative HPLC (Gilson gx-281
  8. waitgradient: 5% to 100% B in 20 min

Sources & evidence

ORD record
ord-0f25987e96d740868a118ab580e10933
Source dataset
uspto-grants-2015_03
Patent number
US08975417B2

Reaction notes

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