Reaction #76733

ord-9540ad39a2414b7abb810eca8ddaf9f3

Reaction equation

CCOc1cc(Cc2cnc(N)nc2N)cc2c1ccn2COCC[Si](C)(C)C
5-[4-Ethoxy-1-(2-trimethylsilanyl-ethoxymethyl)-1H-indol-6-ylmethyl]-pyrimidine-2,4-diamine
Cl.N=C(N)N
guanidine hydrochloride
CC(C)(C)[O-].[K+]
potassium tert-butylate
CC(C)(C)[O-].[K+]
potassium tert-butylate
CCOc1cc(C=O)cc2c1ccn2COCC[Si](C)(C)C
4-ethoxy-1-(2-trimethylsilanyl-ethoxymethyl)-1H-indole-6-carbaldehyde
N#CCCNc1ccccc1
3-anilinopropionitrile
CCOc1cc(Cc2cnc(N)nc2N)cc2[nH]ccc12
title compound
Yield 62.0%
CCOc1cc(Cc2cnc(N)nc2N)cc2[nH]ccc12
5-(4-Ethoxy-1H-indol-6-ylmethyl)-pyrimidine-2,4-diamine
Yield 62.0%

Conditions

Detailed conditions
See reaction.notes.procedure_details.

Workup

  1. 1
    Otherthe suspension formed
  2. 2
    FiltrationThe precipitate was collected by filtration
  3. 3
    Otherdried
  4. 4
    Temperaturethe reaction mixture was refluxed for 16 h
  5. 5
    workup.DISTILLATIONmost of the solvent was distilled off
  6. 6
    workup.ADDITIONether (50 mL) was added
  7. 7
    OtherInsoluble material was removed by filtration
  8. 8
    Washthe filtrate was washed with water
  9. 9
    Dryingdried (MgSO4)
  10. 10
    Otherevaporated
  11. 11
    WashThe residue was washed with diethyl ether/n-hexane 4:3 (70 mL)

Procedure

5-[4-Ethoxy-1-(2-trimethylsilanyl-ethoxymethyl)-1H-indol-6-ylmethyl]-pyrimidine-2,4-diamine. A warm solution of potassium tert-butylate (900 mg, 8.02 mmol) in tert-butanol (7.5 mL) was added at room temperature to a solution of 4-ethoxy-1-(2-trimethylsilanyl-ethoxymethyl)-1H-indole-6-carbaldehyde (2.14 g, 6.69 mmol) and 3-anilinopropionitrile (1.08 g, 7.36 mmol) in methyl sulfoxide (25 mL). After 90 min the solution was treated with water and the suspension formed was stirred for 2 h. The precipitate was collected by filtration and dried. This material was added to a suspension of guanidine hydrochloride (1.90 g, 19.9 mmol) and potassium tert-butylate (2.23 g, 19.9 mmol) in ethanol (100 mL), and the reaction mixture was refluxed for 16 h, then most of the solvent was distilled off, and ether (50 mL) was added. Insoluble material was removed by filtration, the filtrate was washed with water, dried (MgSO4), and evaporated. The residue was washed with diethyl ether/n-hexane 4:3 (70 mL) to afford the title compound (1.71 g, 62%). Light brown solid.

Source

DOI: 10.6084/m9.figshare.5104873.v1Patent: US06703397B2uspto-grants-2004_03