反応 #53414

反応方程式

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

1-H-pyrazolecarboxamidine hydrochloride

4-aminoethylaniline

diisopropylethylamine

NaOH

→

83

収率 11.0%

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

収率 11.0%

溶媒

methanol

ether

DMF

反応条件

後処理

1. 1
   その他to produce a clear oil
2. 2
   洗浄The obtained oil (82) was washed with ether
3. 3
   その他dried under vacuum (40 mTorr) overnight
4. 4
   乾燥After 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
   温度at reflux
10. 10
    温度cooled to room temperature
11. 11
    その他the solvent was removed under reduced pressure
12. 12
    workup.DISSOLUTIONThe residue was dissolved in a minimal volume of DMF
13. 13
    その他separated by preparative HPLC
14. 14
    workup.ADDITIONThe fractions containing product with M+H=349
15. 15
    その他were collected
16. 16
    その他the solvent was removed under reduced pressure
17. 17
    workup.DISSOLUTIONThe residue was dissolved in 10% HCl
18. 18
    その他evaporated to dryness

実験手順

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]+.

出典