Реакция #168495

Уравнение реакции

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

1-H-pyrazolecarboxamidine hydrochloride

4-aminoethylaniline

diisopropylethylamine

NaOH

→

83

Выход 11.0%

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

Выход 11.0%

Растворители

methanol

ether

DMF

Условия реакции

Обработка

1. 1
   Другоеto produce a clear oil
2. 2
   ПромывкаThe obtained oil (82) was washed with ether
3. 3
   Другоеdried under vacuum (40 mTorr) overnight
4. 4
   СушкаAfter 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
   Температураat reflux
10. 10
    Температураcooled to room temperature
11. 11
    Другоеthe solvent was removed under reduced pressure
12. 12
    workup.DISSOLUTIONThe residue was dissolved in a minimal volume of DMF
13. 13
    Другоеseparated by preparative HPLC
14. 14
    workup.ADDITIONThe fractions containing product with M+H=349
15. 15
    Другоеwere collected
16. 16
    Другоеthe solvent was removed under reduced pressure
17. 17
    workup.DISSOLUTIONThe residue was dissolved in 10% HCl
18. 18
    Другоеevaporated to dryness

Методика

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]+.

Источник