반응 #53414

반응 방정식

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

1-H-pyrazolecarboxamidine hydrochloride

4-aminoethylaniline

diisopropylethylamine

NaOH

→

83

수율 11.0%

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

수율 11.0%

용매

methanol

ether

DMF

반응 조건

후처리

1. 1
   기타to produce a clear oil
2. 2
   세척The obtained oil (82) was washed with ether
3. 3
   기타dried under vacuum (40 mTorr) overnight
4. 4
   건조After 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
   온도at reflux
10. 10
    온도cooled to room temperature
11. 11
    기타the solvent was removed under reduced pressure
12. 12
    workup.DISSOLUTIONThe residue was dissolved in a minimal volume of DMF
13. 13
    기타separated by preparative HPLC
14. 14
    workup.ADDITIONThe fractions containing product with M+H=349
15. 15
    기타were collected
16. 16
    기타the solvent was removed under reduced pressure
17. 17
    workup.DISSOLUTIONThe residue was dissolved in 10% HCl
18. 18
    기타evaporated to dryness

실험 절차

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]+.

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