Ammonium Hydroxide → 6-{2-Methoxy-4-[3-((R)-2-methyl-pyrrolidin-1-yl)-propoxy]-phenyl}-2H-pyridazin-3-one

HRID 2042635Notes

Reaction equation

HRID 2042635 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH2:10][CH2:11][CH2:12][N:13]2[CH2:17][CH2:16][CH2:15][C@H:14]2[CH3:18])[CH:6]=[CH:5][C:4]=1[C:19](=O)[CH3:20].O.[C:23]([OH:27])(=O)[CH:24]=O.[NH4+:28].[OH-].O.[NH2:31]N.C([O-])(O)=O.[Na+]>C(O)(=O)C.O>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH2:10][CH2:11][CH2:12][N:13]2[CH2:17][CH2:16][CH2:15][C@H:14]2[CH3:18])[CH:6]=[CH:5][C:4]=1[C:19]1[CH:20]=[CH:24][C:23](=[O:27])[NH:28][N:31]=1

Participants

8

Reactant 5

HCID 14923Ammonium HydroxideHCID 24654Hydrazine hydrate (1:1)HCID 516892Sodium BicarbonateHCID 15620607Glyoxylic acid, monohydrateHCID 596519361-{2-Methoxy-4-[3-((R)-2-methyl-pyrrolidin-1-yl)-propoxy]-phenyl}-ethanone

Product 1

HCID 566803716-{2-Methoxy-4-[3-((R)-2-methyl-pyrrolidin-1-yl)-propoxy]-phenyl}-2H-pyridazin-3-one

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Procedure

In a 100 mL round bottom flask, 1-{2-methoxy-4-[3-((R)-2-methyl-pyrrolidin-1-yl)-propoxy]-phenyl}-ethanone (4.24 g, 14.5 mmol), and glyoxylic acid monohydrate (2.01 g, 21.8 mmol), in acetic acid (20 mL) was heated to reflux 3 h. The reaction was cooled and diluted with water (40 mL). The mixture was basified to pH 8 with NH4OH and then hydrazine monohydrate (1.41 mL, 29.1 mmol) was added. The reaction was heated to reflux 2 h. The reaction was cooled and re-basified with NaHCO3, then extracted with methylene chloride three times. The organics were dried over MgSO4, then ethereal HCL was added. The solvents were removed under vacuum and the product was crystallized with MeOH/ether to produce 500 mg (9%). Mp 182-186° C. MS m/z 344 (M+H).

Workup

  1. temperatureto reflux 3 h
  2. temperatureThe reaction was cooled
  3. temperatureThe reaction was heated
  4. temperatureto reflux 2 h
  5. extractionextracted with methylene chloride three times
  6. dry with materialThe organics were dried over MgSO4
  7. additionethereal HCL was added
  8. customThe solvents were removed under vacuum
  9. customthe product was crystallized with MeOH/ether
  10. customto produce 500 mg (9%)

Sources & evidence

ORD record
ord-21f0c234d47d4640a22c3b9e67b01f00
Source dataset
uspto-grants-2013_11
Patent number
US08586588B2

Reaction notes

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