Dichloromethane → HCID 10019969, compound

HRID 2375376Notes

Reaction equation

HRID 2375376 reaction equation
[C:1]([C:4]1[CH:8]=[C:7]([CH3:9])[N:6]([C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][C:11]=2[O:18][CH3:19])[C:5]=1[CH3:20])(=O)[CH3:2].[CH2:21]1[CH:23]([C:24](Cl)=O)C1.[Sn](Cl)(Cl)(Cl)Cl.[CH2:32](Cl)Cl.[NH2:35][NH2:36]>C1(C)C=CC=CC=1.[OH-].[Na+].C(O)C.O>[CH:23]1([C:32]2[C:8]3=[C:7]([CH3:9])[N:6]([C:10]4[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][C:11]=4[O:18][CH3:19])[C:5]([CH3:20])=[C:4]3[C:1]([CH3:2])=[N:36][N:35]=2)[CH2:24][CH2:21]1

Participants

10

Reactant 5

HCID 6344DichloromethaneHCID 9321HydrazineHCID 24287Tin tetrachlorideHCID 77637Cyclopropanecarbonyl chlorideHCID 393723951-[1-(2,4-Dimethoxyphenyl)-2,5-dimethyl-1H-pyrrol-3-yl]ethan-1-one

Product 1

HCID 10019969HCID 10019969, compound

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 14798Sodium HydroxideSolvent

Procedure

To a solution of 3-acetyl-1-(2,4-dimethoxyphenyl)-2,5-dimethylpyrrole (273 mg, 1.0 mmol) in toluene (5 mL) at −78° C. was added 3-cyclopropanecarbonyl chloride (0.11 mL, 1.2 mmol) followed by dropwise addition of a 1.0M solution of tin(IV) chloride in CH2Cl2 (1.2 mL, 1.2 mmol). The reaction was allowed to warm to room temp overnight. The solution was diluted with 0.25M NaOH, extracted with EtOAc, the organic layer washed with brine, dried over MgSO4, filtered, concentrated in vacuo, and purified by flash chromatography (10-25% EtOAc/hexanes) to give the dione (MS (ESI) 342 (M +H)+). The dione was taken up in ethanol (5 mL) and excess hydrazine (0.1 mL) was added. The solution was stirred at 40° C. overnight, poured into water, and filtered to give 1-(cyclopropyl)-6-(2,4-dimethoxyphenyl)-4,5,7-trimethyl-6H-pyrrolo[3,4-d]pyridazine as a white solid: 1H NMR (CDCl3, 500 MHz) δ 7.03 (dd, 1H), 6.66-6.56 (m, 2H), 3.90 (s, 3H), 3.75 (s, 3H), 2.75 (s, 3H), 2.47 (s, 3H), 2.39 (quintet, 1H), 2.38 (s, 3H), 1.35-1.28 (m, 2H), 0.97 (dd, 2H); MS (ESI) 338 (M+H)+.

Workup

  1. extractionextracted with EtOAc
  2. washthe organic layer washed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. custompurified by flash chromatography (10-25% EtOAc/hexanes)
  7. customto give the dione (MS (ESI) 342 (M +H)+)
  8. filtrationfiltered

Sources & evidence

ORD record
ord-a5038d784d844652bf6f32dfc5a1bbff
Source dataset
uspto-grants-2008_12
Patent number
US07465730B2

Reaction notes

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