* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Reference：
[1] Helvetica Chimica Acta, 1958, vol. 41, p. 1806,1812
2
[ 5177-27-5 ]
[ 124-41-4 ]
[ 96833-41-9 ]
Yield
Reaction Conditions
Operation in experiment
91%
at 20℃; for 1.5 h;
Preparation 164 2-Chloro-4-methoxypyrimidin-5-amine Sodium methoxide (0.5M in methanol, 3.7 mL, 1.829 mmol) was added to a solution of 2,4-dichloropyrimidin-5-amine (0.2 g, 1.220 mmol) in MeOH (2.5 mL). The reaction was stirred at room temperature for 1.5 hours. The reaction was then diluted with EtOAc and quenched with water. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic layers were dried (Na2SO4), filtered and concentrated under reduced pressure to afford the title product as a brown solid (177 mg, 91percent). 1H NMR (500 MHz, CDCl3): δ 3.93 (s, 3H), 5.31 (br s, 2H), 7.73 (s, 1H). LC (Method B)-MS (ESI, m/z) tR 1.6 min, 160 [M+H]+
83%
at 0 - 20℃; for 66 h; Inert atmosphere
5.4Msodium methoxide (100 μ, 0.54 mmol) was added dropwise to a stirring solutionof 2,4-dichloropyrimidin-5 -amine (89 mg, 0.54 mmol) in methanol (2 mL) at 0 °Cunder nitrogen. The reaction was allowed to warm to room temperature andstirred for 1 hr. The reaction was treated with more 5.4M sodium methoxide (10μ) and stirred for a further 1 hr, then left to stand at room temperature for64 hrs. The reaction was quenched with acetic acid (1 mL) and concentrated invacuo. The residue was dissolved in EtOAc (20 mL) and washed with saturatedaqueous NaHC03 (2 x 6 mL), brine (6 mL), dried over Na2SC>4,filtered and the filtrate was concentrated in vacuo. The residue obtained waspurified by flash column chromatography over silica (Biotage 10 g SNAPcartridge) eluting with heptane:EtOAc , smooth gradient 1 :0 to 7:3 to affordthe title compound as a white solid (80 mg, 83percent) ; H NMR (500 MHz,DMSO) δ 3.93 (s, 3H), 5.31 (s, 2H), 7.72 (s, 1H).
0.35 g
for 16 h; Reflux
A mixture of 2,4-dichloropyrimidin-5-amine (0.5 g, 3.04 mmol), sodium methoxide (0.66 g, 12.19 mmol) and methanol (10 ml) was refluxed for 16 hours. The solvent was removed under reduced pressure. Water was added and the aqueous phase was extracted with ethyl acetate. The organic phase was washed with water and brine, dried over sodium sulphate and concentrated under reduced pressure. The yield of 2-chloro-4-methoxypyrimidin-5-amine after flash chromatography (100-200 mesh size silica gel, 20-25percent ethyl acetate in hexane) was 0.35 g. N-Bromosuccinimide (67 mg, 0.37 mmol) was added to a solution of 2-chloro-4-methoxypyrimidin-5-amine (50 mg, 0.31 mmol) in chloroform (2 ml) and the resulting mixture was stirred at RT for 3 hours. Water was added and the mixture extracted with chloroform. The organic phase was washed with water and brine, dried over sodium sulphate and concentrated under reduced pressure. The yield of 4-bromo-2-chloro-6-methoxypyrimidin-5-amine was 60 mg.
Preparation 164: 2-Chloro-4-methoxypyrimidin-5-amine; [00336] Sodium methoxide (0.5M in methanol, 3.7ml_, 1 .829mmol) was added to a solution of 2,4-dichloropyrimidin-5-amine (0.2g, 1 .220mmol) in MeOH (2.5ml_). The reaction was stirred at room temperature for 1 .5 hours. The reaction was then diluted with EtOAc and quenched with water. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic layers were dried (Na2S04), filtered and concentrated under reduced pressure to afford the title product as a brown solid (177mg, 91 percent).1 H NMR (500MHz, CDCI3): δ 3.93 (s, 3H), 5.31 (br s, 2H), 7.73 (s, 1 H). LC (Method B)-MS (ESI, m/z) fR 1 .6 min, 160 [M+H]+
With palladium 10% on activated carbon; hydrogen; sodium hydroxide; In tetrahydrofuran; at 20.0℃; for 24.0h;
A mixture of 2,4-dichloropyrimidin-5 -amine (400 mg, 2.439 mmol), ethanol (12.200 g, 265 mmol), NaOH (195 mg, 4.88 mmol) and 10% palladium on carbon (260 mg, 0.122 mmol) in THF (4 mL) was stirred under a hydrogen atmosphere at room temperature for 24 h. The mixture was concentrated and the residue was purified by column chromatography on silica gel (40%? 70% ethyl acetate in hexanes; 25 g column) to afford 4-ethoxypyrimidin-5 -amine (140 mg, 1.006 mmol, 41% yield) as a yellow solid: NMR (400MHz, DMSO-de) delta 8.03 (s, 1H), 7.85 (s, 1H), 5.07 (s, 2H), 4.39 (q, J=7.0 Hz, 2H), 1.35 (t, J=7.0 Hz, 3H); LCMS (ESI) mle 140.1 [(M+H) + , calcd for CeHioNsO 140.1].
(7S)-2-chloro-7-((R)-1-methoxyethyl)-7,8-dihydropteridin-6(5H)-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
54%
With N-ethyl-N,N-diisopropylamine; In ethanol; at 100℃; for 16.0h;
Step 1: (7S)-2-Chloro-7-((R)-1-methoxyethyl)-7,8-dihydropteridin-6(5H)-one (2S,3R)-2-Amino-3-methoxy-butanoic acid (1 g, 7.5 mmol), 2,4-dichloropyrimidin-5-amine (1000 mg, 6.1 mmol), and N,N-diisopropylethylamine (3.2 mL, 18.23 mmol) was taken into ethanol (15 mL) and heated at 100 C. for 16 hours. The reaction was cooled to room temperature. A precipitate formed upon cooling. The precipitate was collected by vacuum filtration, washed with hexanes, and dried to provide the desired product (800 mg, 54%); ESMS(M+1)=243.12.
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