Reacción #53414

Ecuación de reacción

3,5-diamino-6-chloropyrazine-2 carboxylic acid methyl ester

1-H-pyrazolecarboxamidine hydrochloride

4-aminoethylaniline

diisopropylethylamine

NaOH

→

83

Rendimiento 11.0%

4-(4-Aminophenyl)ethylamidino-3,5-diamino-6-chloropyrazinecarboxamide Hydrochloride

Rendimiento 11.0%

Disolventes

methanol

ether

DMF

Condiciones de reacción

Tratamiento posterior

1. 1
   Otroto produce a clear oil
2. 2
   LavadoThe obtained oil (82) was washed with ether
3. 3
   Otrodried under vacuum (40 mTorr) overnight
4. 4
   SecadoAfter drying 70 mg of oil
5. 5
   workup.ADDITIONwas added
6. 6
   workup.ADDITIONwas added
7. 7
   workup.ADDITIONthe resulting solution was added to the reaction mixture
8. 8
   workup.STIRRINGThe reaction mixture was stirred 3 h
9. 9
   Temperaturaat reflux
10. 10
    Temperaturacooled to room temperature
11. 11
    Otrothe solvent was removed under reduced pressure
12. 12
    workup.DISSOLUTIONThe residue was dissolved in a minimal volume of DMF
13. 13
    Otroseparated by preparative HPLC
14. 14
    workup.ADDITIONThe fractions containing product with M+H=349
15. 15
    Otrowere collected
16. 16
    Otrothe solvent was removed under reduced pressure
17. 17
    workup.DISSOLUTIONThe residue was dissolved in 10% HCl
18. 18
    Otroevaporated to dryness

Procedimiento

A mixture of 1-H-pyrazolecarboxamidine hydrochloride (2.8 g, 19 mmol), 4-aminoethylaniline (1.3 mL, 9 mmol) and diisopropylethylamine (1.3 ml) were stirred in dry DMF (5 mL) under argon for 18 h. After this time, ether (30 ml) was added to produce a clear oil. The obtained oil (82) was washed with ether and dried under vacuum (40 mTorr) overnight. After drying 70 mg of oil was taken into dry methanol (3 mL) and 25% NaOH (0.14 mL) was added. The reaction volume was decreased to 1.0 mL and 3,5-diamino-6-chloropyrazine-2 carboxylic acid methyl ester (0.1 g, 0.5 mmol) was added. The mixture was stirred at room temperature overnight. Another portion of 82 (0.1 g) was dissolved in methanol (1 mL), treated with 25% NaOH (0.15 mL) and the resulting solution was added to the reaction mixture. The reaction mixture was stirred 3 h at reflux, then cooled to room temperature and the solvent was removed under reduced pressure. The residue was dissolved in a minimal volume of DMF and separated by preparative HPLC. The obtained fractions were analyzed by LC/MS. The fractions containing product with M+H=349 were collected and the solvent was removed under reduced pressure. The residue was dissolved in 10% HCl and evaporated to dryness to produce 83 (23.5 mg, 11%) as a yellow solid. 1H NMR (360 MHz, DMSO-d6) δ 2.91 (m, 2H), 3.59 (m, 2H), 7.31 (d, 2H), 7.42 (m, 4H), 9.02 (br s., 2H), 9.41 (br s., 1H), 10.56 (s, 1H). 13C NMR (90 MHz, DMSO-d6) 33.1, 42.0, 108.9, 119.6, 120.7, 129.9(2C), 131.0(2C), 153.1, 154.1, 155.8, 165.2. API MS m/z=349 [C14H17ClN8O+H]+.

Fuente