Ethyl Acetate → 3-methoxycarbonyl-1-(7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-indole

HRID 1869177

Reaction equation

HRID 1869177 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[NH:7][CH:6]=1)=[O:4].[H-].[Na+].Cl[C:17]1[C:18]2[CH:25]=[CH:24][N:23]([CH3:26])[C:19]=2[N:20]=[CH:21][N:22]=1.C(OCC)(=O)C>CN(C)C=O.O>[CH3:1][O:2][C:3]([C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[N:7]([C:17]2[C:18]3[CH:25]=[CH:24][N:23]([CH3:26])[C:19]=3[N:20]=[CH:21][N:22]=2)[CH:6]=1)=[O:4]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 2658294-Chloro-7-methyl-7H-pyrrolo[2,3-d]pyrimidineHCID 589098Methyl indole-3-carboxylate

Product 1

HCID 689686143-methoxycarbonyl-1-(7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-indole

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
20 °C

Procedure

1.40 g (8 mmol) of 3-methoxycarbonyl-1H-indole are added to 30 cm3 of dimethylformamide at a temperature in the region of 20° C. under an argon atmosphere, and 0.32 g (10 mmol) of sodium hydride are then added. The reaction mixture is stirred at a temperature in the region of 20° C. for 1 hour, 1.35 g (8.05 mmol) of 4-chloro-7-methyl-7H-pyrrolo[2,3-d]pyrimidine in 10 cm3 of dimethylformamide are then added, and the mixture is heated at a temperature in the region of 100° C. for 16 hours. The reaction mixture is then cooled to a temperature in the region of 20° C. and then poured into a mixture of 200 cm3 of ethyl acetate and 200 cm3 of water. The organic phase is separated out after the phases have settled, washed with twice 200 cm3 of water and then with 200 cm3 of saturated aqueous sodium chloride solution, and then dried over magnesium sulphate and concentrated to dryness under reduced pressure (2.7 kPa). The residue is purified by flash chromatography on silica gel [eluent: cyclohexane/ethyl acetate (80/20 by volume)]. After the fractions containing the expected product have been concentrated to dryness under reduced pressure (2.7 kPa), 1.35 g of 3-methoxycarbonyl-1-(7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-indole are obtained in the form of an off-white solid. Mass spectrum (EI): m/e 306 (M+) (base peak).

Workup

  1. temperaturethe mixture is heated at a temperature in the region of 100° C. for 16 hours
  2. temperatureThe reaction mixture is then cooled to a temperature in the region of 20° C.
  3. customThe organic phase is separated out after the phases
  4. washwashed with twice 200 cm3 of water
  5. dry with materialwith 200 cm3 of saturated aqueous sodium chloride solution, and then dried over magnesium sulphate
  6. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  7. customThe residue is purified by flash chromatography on silica gel [eluent: cyclohexane/ethyl acetate (80/20 by volume)]
  8. additionAfter the fractions containing the expected product
  9. concentrationhave been concentrated to dryness under reduced pressure (2.7 kPa), 1.35 g of 3-methoxycarbonyl-1-(7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-indole
  10. customare obtained in the form of an off-white solid

Sources & evidence

ORD record
ord-b106c521b4884d099a39c1da7ce9cef3
Source dataset
uspto-grants-2009_12
Patent number
US07638521B2

Linked notes

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