Reaktion #168495

Reaktionsgleichung

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

1-H-pyrazolecarboxamidine hydrochloride

4-aminoethylaniline

diisopropylethylamine

NaOH

→

83

Ausbeute 11.0%

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

Ausbeute 11.0%

Lösungsmittel

methanol

ether

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeto produce a clear oil
2. 2
   WaschenThe obtained oil (82) was washed with ether
3. 3
   Sonstigedried under vacuum (40 mTorr) overnight
4. 4
   TrocknenAfter 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
   Temperaturat reflux
10. 10
    Temperaturcooled to room temperature
11. 11
    Sonstigethe solvent was removed under reduced pressure
12. 12
    workup.DISSOLUTIONThe residue was dissolved in a minimal volume of DMF
13. 13
    Sonstigeseparated by preparative HPLC
14. 14
    workup.ADDITIONThe fractions containing product with M+H=349
15. 15
    Sonstigewere collected
16. 16
    Sonstigethe solvent was removed under reduced pressure
17. 17
    workup.DISSOLUTIONThe residue was dissolved in 10% HCl
18. 18
    Sonstigeevaporated to dryness

Vorschrift

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]+.

Quelle