Methanol → 1-Chloro-4-methyl-6,7,8,9-tetrahydropyridazino[4,5-b]indolizine

HRID 1292070Notes

Reaction equation

HRID 1292070 reaction equation
[CH3:1][C:2]1[C:14]2[N:13]3[C:8]([CH2:9][CH2:10][CH2:11][CH2:12]3)=[CH:7][C:6]=2[C:5](=O)[NH:4][N:3]=1.O=P(Cl)(Cl)[Cl:18].CO.[OH-].[Na+]>C(Cl)Cl>[Cl:18][C:5]1[C:6]2[CH:7]=[C:8]3[N:13]([C:14]=2[C:2]([CH3:1])=[N:3][N:4]=1)[CH2:12][CH2:11][CH2:10][CH2:9]3

Participants

6

Reactant 4

HCID 887MethanolHCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 867526156,7,8,9-Tetrahydro-4-(methyl)pyridazino[4,5-b]indolizin-1-one

Product 1

HCID 867526161-Chloro-4-methyl-6,7,8,9-tetrahydropyridazino[4,5-b]indolizineYield 92%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Compound XI (3.00 g, 15 mmol) was heated under reflux with excess POCl3 (25 mL) until no starting material remained (TLC, silic gel, 5% methanol in methylene chloride), then poured over ice, made basic with aqueous sodium hydroxide and the aqueous phase extracted with methylene chloride to isolate the product. The organic phase was dried (MgSO4), filtered, and evaporated to give a residue which was purified by flash column chromatography (silica gel, 5% methanol in methylene chloride) to give 1-chloro-4-methyl-6,7,8,9-tetrahydropyridazino[4,5-b]indolizine XII (3.00 g, 92%)

Workup

  1. additionpoured over ice
  2. extractionthe aqueous phase extracted with methylene chloride
  3. customto isolate the product
  4. dry with materialThe organic phase was dried (MgSO4)
  5. filtrationfiltered
  6. customevaporated
  7. customto give a residue which
  8. customwas purified by flash column chromatography (silica gel, 5% methanol in methylene chloride)

Sources & evidence

ORD record
ord-c0a2361f749148a4a1e86312db4f23d9
Source dataset
uspto-grants-1998_05
Patent number
US05756501

Reaction notes

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