Water → Methyl 1-(isoquinolin-1-yl)-4-methyl-1H-pyrrole-3-carboxylate

HRID 1792809Notes

Reaction equation

HRID 1792809 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]([C:7]1[C:11]([CH3:12])=[CH:10][NH:9][CH:8]=1)=[O:6].Cl[C:14]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:17]=[CH:16][N:15]=1.O>CN(C)C=O>[C:14]1([N:9]2[CH:10]=[C:11]([CH3:12])[C:7]([C:5]([O:4][CH3:3])=[O:6])=[CH:8]2)[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:17]=[CH:16][N:15]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 140539Isoquinoline, 1-chloro-HCID 15274278Methyl 4-methyl-1H-pyrrole-3-carboxylate

Product 1

HCID 22024933Methyl 1-(isoquinolin-1-yl)-4-methyl-1H-pyrrole-3-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
40 °C

Procedure

0.208 g (6.5 mmol) of sodium hydride, at 75% by weight in liquid petroleum jelly, is added at a temperature in the region of 20° C. under an argon atmosphere to a solution of 0.903 g (6.5 mmol) of 3-methoxycarbonyl-4-methyl-1H-pyrrole in 20 mL of dimethylformamide. After stirring at a temperature in the region of 40° C. for 0.3 hour, 1.07 g (6.5 mmol) of 1-chloroisoquinoline and 10 mL of dimethylformamide are added. After stirring at a temperature in the region of 120° C. for 4 hours, the reaction mixture is poured into 200 mL of salt water and then extracted with 100 mL of ethyl acetate. The organic phase is partially concentrated under reduced pressure. 100 mL of salt water are added to the residue, which is then extracted with 50 mL of ethyl acetate. The organic phase is dried over anhydrous magnesium sulphate, filtered and then concentrated to dryness under reduced pressure (2.7 kPa) to give a solid which is purified by silica gel chromatography [eluent: cyclohexane/dichloromethane/ethyl acetate (60/36/4 by volume)]. After concentrating the fractions under reduced pressure (2.7 kPa), 1.5 g of 1-(isoquinol-1-yl)-3-methoxycarbonyl-4-methyl-1H-pyrrole are obtained. Mass spectrum (EI): m/e 266 (M+.), m/e 235.

Workup

  1. stirringAfter stirring at a temperature in the region of 120° C. for 4 hours
  2. extractionextracted with 100 mL of ethyl acetate
  3. concentrationThe organic phase is partially concentrated under reduced pressure
  4. addition100 mL of salt water are added to the residue, which
  5. extractionis then extracted with 50 mL of ethyl acetate
  6. dry with materialThe organic phase is dried over anhydrous magnesium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  9. customto give a solid which
  10. customis purified by silica gel chromatography [eluent: cyclohexane/dichloromethane/ethyl acetate (60/36/4 by volume)]
  11. concentrationAfter concentrating the fractions under reduced pressure (2.7 kPa), 1.5 g of 1-(isoquinol-1-yl)-3-methoxycarbonyl-4-methyl-1H-pyrrole
  12. customare obtained

Sources & evidence

ORD record
ord-0a24db0bb7c94ee295f37e6984effbc5
Source dataset
uspto-grants-2006_07
Patent number
US07078414B2

Reaction notes

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