Reaction #76735

Reaction equation

guanidine hydrochloride

5-[1-Methyl-4-(2-trimethylsilanyl-ethoxymethoxy)-1H-indol-6-ylmethyl]-pyrimidine-2,4-diamine

potassium tert-butylate

1-methyl-4-(2-trimethylsilanyl-ethoxymethoxy)-1H-indole-6-carbaldehyde

3-anilinopropionitrile

→

MeOH NH4OH

title compound

Yield 43.0%

6-(2,4-Diamino-pyrimidin-5-ylmethyl)-1-methyl-1H-indol-4-ol

Yield 43.0%

Solvents

ethanol

ethyl acetate

tert-butanol

methyl sulfoxide

Conditions

Workup

1. 1
   Washwashed with water and brine
2. 2
   Dryingdried (MgSO4)
3. 3
   Otherevaporated
4. 4
   workup.DISSOLUTIONThis material was dissolved in ethanol (70 mL)
5. 5
   workup.DISTILLATIONMost of the solvent was distilled off
6. 6
   Otherthe residue was partitioned between water and ether
7. 7
   WashThe organic layer was washed with brine
8. 8
   Dryingdried (MgSO4)
9. 9
   Otherevaporated

Procedure

5-[1-Methyl-4-(2-trimethylsilanyl-ethoxymethoxy)-1H-indol-6-ylmethyl]-pyrimidine-2,4-diamine. A warm solution of potassium tert-butylate (2.68 g, 23.4 mmol) in tert-butanol (20 mL) was added to a room temperature solution of 1-methyl-4-(2-trimethylsilanyl-ethoxymethoxy)-1H-indole-6-carbaldehyde (5.95 g, 19.5 mmol) and 3-anilinopropionitrile (3.20 g, 21.4 mmol) in methyl sulfoxide (70 mL). After 2 h the solution was diluted with ethyl acetate, washed with water and brine, dried (MgSO4), and evaporated. This material was dissolved in ethanol (70 mL) and added to a suspension of guanidine hydrochloride (6.21 g, 64.4 mmol) in ethanol (210 mL), and the mixture was stirred at 70° C. for 22 h. Most of the solvent was distilled off, and the residue was partitioned between water and ether. The organic layer was washed with brine, dried (MgSO4), and evaporated. Flash chromatography (SiO2; CH2CL2/MeOH/NH4OH 19:1:0.05) afforded the title compound (3.32 g, 43%).Yellow solid.

Source