CN103232453A - Synthesizing method of 2-amino-5,8-dimethoxy[1,2,4]-triazolo[1,5-c]-pyrimidine - Google Patents
Synthesizing method of 2-amino-5,8-dimethoxy[1,2,4]-triazolo[1,5-c]-pyrimidine Download PDFInfo
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Abstract
The invention relates to a synthesizing method of 2-amino-5,8-dimethoxy[1,2,4]-triazolo[1,5-c]-pyrimidine. The invention solves the problems such as low yield, high pollution, complicated operation, and the like of current preparation methods. The method provided by the invention comprises the steps that: methoxy methyl acetate and methyl formate are condensed under a strong-alkali condition; the condensation product is subjected to cyclization with thiourea; methylation is carried out by using chloromethane; chlorination is carried out by using phosphorus oxychloride; hydrazination is carried out by using hydrazine hydrate; the product is subjected to cyclization with cyano bromine; and under the effect of strong alkali and acrylate, a final product is obtained. With the method provided by the invention, the yield of each step is higher than 80%, and a total yield reaches 39%. The method is suitable for industrialized productions. The method provided by the invention belongs to the field of paddy rice herbicide penoxsulam intermediate preparation.
Description
Technical field
The present invention relates to a kind of synthetic 2-amino-5, the method for 8-dimethoxy [1,2,4]-triazolo [1,5-c]-pyrimidine.
Background technology
2-amino-5,8-dimethoxy [1,2,4]-and triazolo [1,5-c]-pyrimidine is the key intermediate of ultra-high efficiency herbicides for use in paddy penoxsuam, penoxsuam is that The Dow Agrosciences, LLC. was in registration in 2004, promoted in 2005, entered the rice field broad-spectrum herbicide of China market in 2008, to the common multiple weeds of rice terrace, as barnyard grass grass, annual nutgrass flatsedge and multiple broadleaved herb good preventive effect is arranged all.Along with the continuous embodiment of the superior performance of penoxsuam, people continue to increase the penoxsuam demand, therefore its intermediate are studied just to seem significant.
For 2-amino-5,8-dimethoxy [1,2,4]-triazolo [1,5-c]-pyrimidine synthetic, at present modal is to be starting raw material with the 2-methoxy menthyl acetate, under the sodium methylate effect, get the sodium salt of 3-hydroxyl-2-methoxy-methyl acrylate with the methyl-formiate condensation, again with methyl-isothiourea close encircle 2,5-dimethoxy-4 '-hydroxy pyrimidine, then with phosphorus oxychloride under the catalysis of triethylamine, react 4-chloro-2, the 5-dimethoxypyridin, with the hydrazine hydrate reaction, the cyclization of cyano group bromine gets 3-amino-5 again, 8-dimethoxy [1,2,4] triazolo [4,3-c] pyrimidine, at last with sodium methylate reset target product 2-amino-5,8-dimethoxy [1,2,4]-triazolo [1,5-c]-pyrimidine, but this method has a very big drawback, and it is very low to be exactly that sodium salt and the methyl-isothiourea of 3-hydroxyl-2-methoxy-methyl acrylate closes when encircling yield, has only more than 20%, and methylthio group is difficult to change into methoxyl group in this step, has seriously restricted its industrialized realization.
Summary of the invention
The objective of the invention is in order to solve existing preparation 2-amino-5,8-dimethoxy [1,2,4]-triazolo [1,5-c]-the low technical problem of method yield of pyrimidine, provide a kind of 2-amino-5,8-dimethoxy [1,2,4]-synthetic method of triazolo [1,5-c]-pyrimidine.
2-amino-5, the synthetic method of 8-dimethoxy [1,2,4]-triazolo [1,5-c]-pyrimidine is as follows:
One, 3-hydroxyl-2-methoxy-methyl acrylate sodium salt is synthetic:
Make solvent with tetrahydrofuran (THF), alkali is added wherein, drip the mixed solution of being formed at 1: 1 by methoxy menthyl acetate and methyl-formiate mol ratio under the ice-water bath cooling conditions, under 10 ℃-20 ℃ condition, react 5h, reduced pressure goes down to desolventize then, obtains 3-hydroxyl-2-methoxy-methyl acrylate sodium salt;
Two, 2-sulfydryl-5-methoxyl group-4-hydroxy pyrimidine is synthetic:
3-hydroxyl-2-methoxy-methyl acrylate sodium salt is dissolved in the methyl alcohol, add alkali and thiocarbamide again, back flow reaction to reaction finishes, and then is down to room temperature, revolves the steaming desolventizing, be dissolved in water, with hydrochloric acid the pH value is transferred to 3-4, filter, washing, 60 ℃ of dryings, obtain 2-sulfydryl-5-methoxyl group-4-hydroxy pyrimidine;
Three, 2-methylthio group-5-methoxyl group-4-hydroxy pyrimidine is synthetic:
2-sulfydryl-5-methoxyl group-4-hydroxy pyrimidine is joined in the sodium hydroxide solution, under 15 ℃-70 ℃ condition, feed methyl chloride, reaction 8h, the frozen water cooling transfers to 4-5 with hydrochloric acid with the pH value, filters, washing 60 ℃ of dryings, obtains 2-methylthio group-5-methoxyl group-4-hydroxy pyrimidine;
Four, 5-methoxyl group-2-methylthio group-4-chloropyrimide is synthetic:
2-methylthio group-5-methoxyl group-4-hydroxy pyrimidine is added in the acetonitrile, add phosphorus oxychloride again, drip triethylamine, be heated to back flow reaction 2h then, be down to room temperature again, then reaction solution is poured in the frozen water, stir, separate out yellow solid, refilter, wash, drying, namely get 5-methoxyl group-2-methylthio group-4-chloropyrimide;
Five, 5-methoxyl group-2-methylthio group-4-diazanyl pyrimidine is synthetic:
5-methoxyl group-2-methylthio group-4-chloropyrimide is joined in the 350ml dehydrated alcohol, adding 63ml mass concentration is 80% hydrazine hydrate aqueous solution, be heated to back flow reaction 1.5h, reaction solution is lowered the temperature with ice-water bath, separate out white solid, filtration, drying namely get 5-methoxyl group-2-methylthio group-4-diazanyl pyrimidine;
Six, 3-amino-5-methylthio group-8-methoxyl group [1,2,4] triazolos [4,3-c] pyrimidine is synthetic:
5-methoxyl group-2-methylthio group-4-diazanyl pyrimidine of 45.0g is joined in the Virahol of 505ml, again 35.2g cyano group bromine is dissolved in the acetonitrile, drip the acetonitrile solution of cyano group bromine, back flow reaction 2.0h is down to room temperature then, reaction solution is poured in the sodium bicarbonate aqueous solution again, stir 1h, white solid is separated out, and filters, 60 ℃ of dryings, namely get 3-amino-5-methylthio group-8-methoxyl group [1,2,4] triazolo [4,3-c] pyrimidine;
Seven, 2-amino-5,8-dimethoxy [1,2,4] triazolos [1,5-c] pyrimidine synthetic:
3-amino-5-methylthio group-8-methoxyl group [1,2,4] triazolo [4 with 30.0g, 3-c] pyrimidine joins in the methanol solution of alkali, adds the 18.4g acrylate, then at 50 ℃ of reaction 8h, reaction solution is lowered the temperature with ice-water bath, stir 1h, filter, 60 ℃ of dryings, namely get 2-amino-5,8-dimethoxy [1,2,4] triazolo [1,5-c] pyrimidine;
Alkali described in the step 1 is sodium methylate, sodium ethylate, sodium hydride, sodium amide, sodium hydroxide or potassium hydroxide;
Alkali described in the step 2 is sodium methylate, sodium ethylate, sodium hydride, sodium amide, sodium hydroxide or potassium hydroxide;
Alkali described in the step 7 is sodium methylate, sodium ethylate, sodium hydride, sodium amide, sodium hydroxide or potassium hydroxide;
Acrylate described in the step 7 is isobornyl acrylate, methyl acrylate, ethyl propenoate, methyl methacrylate, Propenoic acid, 2-methyl, isobutyl ester, methacrylic dodecyl gallate or isobornyl methacrylate.
Sodium hydroxide solution described in the step 3 is dissolved in the 620ml water by 32.6g sodium hydroxide and makes.
Sodium bicarbonate aqueous solution described in the step 6 is dissolved in the 500ml water by 32g sodium hydroxide and makes.
Synthetic route of the present invention is as follows:
The sodium salt of 3-hydroxyl-2-methoxy-methyl acrylate closes ring with active higher thiocarbamide earlier in the inventive method, methylates again, and yield improves greatly, and per step yield is all up to more than 80%.
The present invention uses sodium hydride that alkalescence is strengthened, and seizes the hydrogen on the carbon of carbonyl next door and forms the enol negative ion easilier, has strengthened its nucleophilic addition(Adn) ability and has improved speed of response and yield.
The present invention adopts methyl chloride that the sulfydryl on the pyrimidine ring is methylated, methyl chloride toxicity is lower, cheap and easy to get, the reaction conditions gentleness, and room temperature can be reacted, react the simple adjust pH in back and just can obtain product, simple to operate, and yield can reach, and (methyl-sulfate is the methylating reagent of using always, but their toxicity is all very big more than 90%, it all is strong carcinogen, add the aftertreatment difficulty, the three wastes are difficult to handle, and yield is not very high).
The present invention adopts and to add butyl methacrylate in the reaction system and promote its transposition and methylthio group to be transformed into methoxyl group, and the methyl methacrylate pungency is less, and toxicity is lower, replaced traditional volatile, the butyl acrylate that pungency is very strong.
Embodiment
Technical solution of the present invention is not limited to following cited embodiment, also comprises the arbitrary combination between each embodiment.
Embodiment one: present embodiment 2-amino-5, the synthetic method of 8-dimethoxy [1,2,4]-triazolo [1,5-c]-pyrimidine is as follows:
One, 3-hydroxyl-2-methoxy-methyl acrylate sodium salt is synthetic:
The 400ml tetrahydrofuran (THF) is mixed with 29.0g alkali, ice-water bath is cooled to 5 ℃, under 10 ℃-20 ℃ condition, drip the mixed solution of being formed by 67.4g methoxy menthyl acetate and 48.0g methyl-formiate then, under 10 ℃-20 ℃ condition, react 5h, reduced pressure goes down to desolventize then, obtains 3-hydroxyl-2-methoxy-methyl acrylate sodium salt;
Two, 2-sulfydryl-5-methoxyl group-4-hydroxy pyrimidine is synthetic:
3-hydroxyl-2-methoxy-methyl acrylate sodium salt is added in the 300ml methyl alcohol, add 48.0g thiocarbamide and 50.0g alkali again, back flow reaction 12h is down to room temperature, revolves the steaming desolventizing, add 300ml water, with hydrochloric acid the pH value is transferred to 3-4, filter, washing, 60 ℃ of dryings, obtain 2-sulfydryl-5-methoxyl group-4-hydroxy pyrimidine;
Three, 2-methylthio group-5-methoxyl group-4-hydroxy pyrimidine is synthetic:
58.7g2-sulfydryl-5-methoxyl group-4-hydroxy pyrimidine is joined in the sodium hydroxide solution, under 25 ℃ condition, feed methyl chloride, reaction 8h, the frozen water cooling transfers to 4-5 with hydrochloric acid with the pH value, filters, washing 60 ℃ of dryings, obtains 2-methylthio group-5-methoxyl group-4-hydroxy pyrimidine;
Four, 5-methoxyl group-2-methylthio group-4-chloropyrimide is synthetic:
50.0g2-methylthio group-5-methoxyl group-4-hydroxy pyrimidine is mixed with the 100ml acetonitrile, add the 80.76g phosphorus oxychloride again, drip triethylamine 44.5g, back flow reaction 2h is down to room temperature more then, reaction solution is poured in the 300ml frozen water then, stir, separate out yellow solid, refilter, wash, drying, namely get 5-methoxyl group-2-methylthio group-4-chloropyrimide;
Five, 5-methoxyl group-2-methylthio group-4-diazanyl pyrimidine is synthetic:
53g5-methoxyl group-2-methylthio group-4-chloropyrimide is joined in the 350ml dehydrated alcohol, adding 63ml mass concentration is 80% hydrazine hydrate aqueous solution, be heated to back flow reaction 1.5h, reaction solution is lowered the temperature with ice-water bath, separate out white solid, filtration, drying namely get 5-methoxyl group-2-methylthio group-4-diazanyl pyrimidine;
Six, 3-amino-5-methylthio group-8-methoxyl group [1,2,4] triazolos [4,3-c] pyrimidine is synthetic:
5-methoxyl group-2-methylthio group-4-diazanyl pyrimidine of 45.0g is joined in the Virahol of 505ml, again 35.2g cyano group bromine is dissolved in the 100.0g acetonitrile, drip the acetonitrile solution of cyano group bromine, back flow reaction 2.0h is down to room temperature then, reaction solution is poured in the sodium bicarbonate aqueous solution again, stir 1h, white solid is separated out, and filters, 60 ℃ of dryings, namely get 3-amino-5-methylthio group-8-methoxyl group [1,2,4] triazolo [4,3-c] pyrimidine;
Seven, 2-amino-5,8-dimethoxy [1,2,4] triazolos [1,5-c] pyrimidine synthetic:
3-amino-5-methylthio group-8-methoxyl group [1,2,4] triazolo [4 with 30.0g, 3-c] pyrimidine joins in the methanol solution of alkali, adds the 18.4g acrylate, then at 50 ℃ of reaction 8h, reaction solution is lowered the temperature with ice-water bath, stir 1h, filter, 60 ℃ of dryings, namely get 2-amino-5,8-dimethoxy [1,2,4] triazolo [1,5-c] pyrimidine;
Alkali described in the step 1 is sodium methylate, sodium ethylate, sodium hydride, sodium amide, sodium hydroxide or potassium hydroxide;
Alkali described in the step 2 is sodium methylate, sodium ethylate, sodium hydride, sodium amide, sodium hydroxide or potassium hydroxide;
Alkali described in the step 7 is sodium methylate, sodium ethylate, sodium hydride, sodium amide, sodium hydroxide or potassium hydroxide;
Acrylate described in the step 7 is isobornyl acrylate, methyl acrylate, ethyl propenoate, methyl methacrylate, Propenoic acid, 2-methyl, isobutyl ester, methacrylic dodecyl gallate or isobornyl methacrylate.
Embodiment two: present embodiment and embodiment one are different is that the sodium hydroxide solution described in the step 3 is dissolved in the 620ml water by 32.6g sodium hydroxide and makes.Other is identical with embodiment one.
Embodiment three: present embodiment is different with one of embodiment one or two is that sodium bicarbonate aqueous solution described in the step 6 is dissolved in the 500ml water by 32g sodium hydroxide and makes.Other and one of embodiment one or two are inequality.
Embodiment four: present embodiment is different with one of embodiment one to three is that the methanol solution of the alkali described in the step 7 is dissolved in 300ml methyl alcohol by the 12.0g sodium methylate and makes.Other is identical with one of embodiment one to three.
Embodiment five: what present embodiment was different with one of embodiment one to four is to react 5h in the step 1 under 11 ℃ condition.Other is identical with one of embodiment one to four.
Embodiment six: what present embodiment was different with one of embodiment one to five is to react 5h in the step 1 under 12 ℃ condition.Other is identical with one of embodiment one to five.
Embodiment seven: what present embodiment was different with one of embodiment one to six is to react 5h in the step 1 under 13 ℃ condition.Other is identical with one of embodiment one to six.
Embodiment eight: what present embodiment was different with one of embodiment one to seven is to react 5h in the step 1 under 15 ℃ condition.Other is identical with one of embodiment one to seven.
Embodiment nine: what present embodiment was different with one of embodiment one to eight is to react 5h in the step 1 under 17 ℃ condition.Other is identical with one of embodiment one to eight.
Embodiment ten: what present embodiment was different with one of embodiment one to nine is to react 5h in the step 1 under 18 ℃ condition.Other is identical with one of embodiment one to nine.
Adopt following verification experimental verification effect of the present invention:
Test one:
2-amino-5, the synthetic method of 8-dimethoxy [1,2,4]-triazolo [1,5-c]-pyrimidine is as follows:
One, 3-hydroxyl-2-methoxy-methyl acrylate sodium salt is synthetic:
The 400ml tetrahydrofuran (THF) is mixed with the 29.0g sodium hydride, ice-water bath is cooled to 5 ℃, under 19 ℃ condition, drip the mixed solution of being formed by 67.4g methoxy menthyl acetate and 48.0g methyl-formiate then, under 19 ℃ condition, react 5h, reduced pressure goes down to desolventize then, obtains 3-hydroxyl-2-methoxy-methyl acrylate sodium salt;
Two, 2-sulfydryl-5-methoxyl group-4-hydroxy pyrimidine is synthetic:
3-hydroxyl-2-methoxy-methyl acrylate sodium salt is added in the 300ml methyl alcohol, add 48.0g thiocarbamide and 50.0g sodium methylate again, back flow reaction 12h is down to room temperature, revolves the steaming desolventizing, add 300ml water, with hydrochloric acid the pH value is transferred to 3-4, filter, washing, 60 ℃ of dryings, obtain 2-sulfydryl-5-methoxyl group-4-hydroxy pyrimidine 90.7g (canescence);
Uniting the step total recovery is: 72.5%.m.p.270～271℃；1HNMR(400MHz?CDCl3)δ：3.71(s，3H，-OCH3)，7.06(s，1H，Ar-H)。IR(KBr，cm-1)：3278.1，3125.7，2613.6，1670.4，1645.3，1542.1，1433.1，1255.7，1233.5，1144.8，1002.1，681.8。
Three, 2-methylthio group-5-methoxyl group-4-hydroxy pyrimidine is synthetic:
58.7g2-sulfydryl-5-methoxyl group-4-hydroxy pyrimidine is joined in the sodium hydroxide solution, under 25 ℃ condition, feed methyl chloride, reaction 8h, the frozen water cooling transfers to 4-5 with hydrochloric acid with the pH value, filter, washing 60 ℃ of dryings, obtains 2-methylthio group-5-methoxyl group-4-hydroxy pyrimidine 60.1g (yield: 92.7%, the survey fusing point is: 197 ℃～200 ℃, detecting its purity with high performance liquid phase is 99.10%);
m.p.197～200℃；1H?NMR(400MHz，CDCl3)δ：2.58(s，3H，-SCH3)，3.86(s，3H，-OCH3)，7.46(s，1H，Ar-H)。IR(KBr，cm-1)：3057.3，2990.7，2789.2，1609.6，1581.7，1543.1，1480.4，1267.3，1154.4，1009.7，866.08，786.9，668.3。
Four, 5-methoxyl group-2-methylthio group-4-chloropyrimide is synthetic:
50.0g2-methylthio group-5-methoxyl group-4-hydroxy pyrimidine is mixed with the 100ml acetonitrile, add the 80.76g phosphorus oxychloride again, drip triethylamine 44.5g, then back flow reaction 2h, be down to room temperature again, then reaction solution is poured in the 300ml frozen water, stirred, separate out yellow solid, refilter, wash, drying, namely get 5-methoxyl group-2-methylthio group-4-chloropyrimide 50.0g (productive rate: 90.32%, survey fusing point and be: 74 ℃～76 ℃, detecting its purity with high performance liquid phase is 99.58%);
m.p.74～76℃；1H?NMR(400MHz?CDCl3)δ：2.56(s，3H，-SCH3)，3.97(s，3H，-OCH3)，8.17(s，1H，Ar-H)。IR(KBr，cm-1)：3028.3，2937.7，1568.1，1521.9，1460.1，1434.1，1406.1，1384.9，1268.2，1231.6，1173.7，1105.2，1002.0，904.6，854.5，728.1，705.9，648.1。
Five, 5-methoxyl group-2-methylthio group-4-diazanyl pyrimidine is synthetic:
53g5-methoxyl group-2-methylthio group-4-chloropyrimide is joined in the 350ml dehydrated alcohol, adding 63ml mass concentration is 80% hydrazine hydrate aqueous solution, be heated to back flow reaction 1.5h, reaction solution is lowered the temperature with ice-water bath, separate out white solid, filtration, drying namely get 5-methoxyl group-2-methylthio group-4-diazanyl pyrimidine 45.1g (yield: 87.11%, fusing point is 117 ℃～120 ℃, and detecting its purity with high performance liquid phase is 98.89%);
M.p.117～120 ℃; 1H NMR (400MHz CDCl3) δ: 2.52 (s, 3H ,-SCH3), 3.75 (s, 2H,-NH-NH2), 3.83 (s, 3H ,-OCH3), 6.52 (s, 1H ,-NH-NH2), 7.62 (s, 1H, Ar-H) .IR (KBr, cm-1): 3321.6,3188.4,3038.9,2926.1 (broad peaks of these a series of compositions), 1576.8,1487.2,1365.6,1256.6,1007.8,935.5,727.1,635.6.
Six, 3-amino-5-methylthio group-8-methoxyl group [1,2,4] triazolos [4,3-c] pyrimidine is synthetic:
5-methoxyl group-2-methylthio group-4-diazanyl pyrimidine of 45.0g is joined in the Virahol of 505ml, again 35.2g cyano group bromine is dissolved in the 100.0g acetonitrile, drip the acetonitrile solution of cyano group bromine, back flow reaction 2.0h then, be down to room temperature, reaction solution is poured in the sodium bicarbonate aqueous solution again, stirred 1h, white solid is separated out, filter, 60 ℃ of dryings, namely get 3-amino-5-methylthio group-8-methoxyl group [1,2,4] triazolo [4,3-c] and pyrimidine 36.7g (yield: 79.1%, the fusing point of compound is 183 ℃～185 ℃, detecting its purity with high performance liquid phase is 97.0%);
m.p.183～185℃；1H?NMR(400MHz，CDCl3)δ：2.74(s，3H，-SCH3)，4.03(s，3H，-OCH3)，6.10(s，2H，-NH2)，7.16(s，1H，Ar-H)。IR(KBr，cm-1)：3378.7，3089.7，1653.1，1601.2，1488.1，1452.6，1321.3，1296.2，1245.1，1159.2，1082.1，1041.6，986.6，966.3，834.2，739.7，688.6。
Seven, 2-amino-5,8-dimethoxy [1,2,4] triazolos [1,5-c] pyrimidine synthetic:
3-amino-5-methylthio group-8-methoxyl group [1,2,4] triazolo [4 with 30.0g, 3-c] pyrimidine joins in the methanol solution of sodium methylate, adds the 18.4g butyl methacrylate, then at 50 ℃ of reaction 8h, reaction solution is lowered the temperature with ice-water bath, stir 1h, filter, 60 ℃ of dryings, namely get 2-amino-5,8-dimethoxy [1,2,4] triazolo [1,5-c] pyrimidine 25.4g (yield: 92.8%, fusing point is 190 ℃～193 ℃, and detecting its purity with high performance liquid phase is 98.3%);
m.p.190～193℃；1H?NMR(400MHz，DMSO)δ：3.90(s，3H，-SCH3)，4.06(s，3H，-OCH3)，6.28(s，2H，-NH2)，7.49(s，1H，Ar-H)IR(KBr，cm-1)：3363.7，3216.4，1683.1，1653.2，1575.9，1465.1，1429.6，1362.3，1281.2，1248.1，1185.2，1165.1，980.8，879.5，834.2，763.7，617.2。
This test synthetic route is as follows:
Claims (10)
1.2-amino-5, the synthetic method of 8-dimethoxy [1,2,4]-triazolo [1,5-c]-pyrimidine is characterized in that 2-amino-5, and the synthetic method of 8-dimethoxy [1,2,4]-triazolo [1,5-c]-pyrimidine is as follows:
One, 3-hydroxyl-2-methoxy-methyl acrylate sodium salt is synthetic:
The 400ml tetrahydrofuran (THF) is mixed with 29.0g alkali, ice-water bath is cooled to 5 ℃, under 10 ℃-20 ℃ condition, drip the mixed solution of being formed by 67.4g methoxy menthyl acetate and 48.0g methyl-formiate then, under 10 ℃-20 ℃ condition, react 5h, reduced pressure goes down to desolventize then, obtains 3-hydroxyl-2-methoxy-methyl acrylate sodium salt;
Two, 2-sulfydryl-5-methoxyl group-4-hydroxy pyrimidine is synthetic:
3-hydroxyl-2-methoxy-methyl acrylate sodium salt is added in the 300ml methyl alcohol, add 48.0g thiocarbamide and 50.0g alkali again, at 40 ℃-60 ℃ reaction 12h, be down to room temperature, revolve the steaming desolventizing, add 300ml water, with hydrochloric acid the pH value is transferred to 3-4, filter, washing, 60 ℃ of dryings, obtain 2-sulfydryl-5-methoxyl group-4-hydroxy pyrimidine;
Three, 2-methylthio group-5-methoxyl group-4-hydroxy pyrimidine is synthetic:
58.7g2-sulfydryl-5-methoxyl group-4-hydroxy pyrimidine is joined in the sodium hydroxide solution, under 15 ℃-70 ℃ condition, feed methyl chloride, reaction 8h, the frozen water cooling transfers to 4-5 with hydrochloric acid with the pH value, filters, washing 60 ℃ of dryings, obtains 2-methylthio group-5-methoxyl group-4-hydroxy pyrimidine;
Four, 5-methoxyl group-2-methylthio group-4-chloropyrimide is synthetic:
50.0g2-methylthio group-5-methoxyl group-4-hydroxy pyrimidine is mixed with the 100ml acetonitrile, add the 80.76g phosphorus oxychloride again, drip triethylamine 44.5g, back flow reaction 2h is down to room temperature more then, reaction solution is poured in the 300ml frozen water then, stir, separate out yellow solid, refilter, wash, drying, namely get 5-methoxyl group-2-methylthio group-4-chloropyrimide;
Five, 5-methoxyl group-2-methylthio group-4-diazanyl pyrimidine is synthetic:
53g5-methoxyl group-2-methylthio group-4-chloropyrimide is joined in the 350ml dehydrated alcohol, adding 63ml mass concentration is 80% hydrazine hydrate aqueous solution, be heated to back flow reaction 1.5h, reaction solution is lowered the temperature with ice-water bath, separate out white solid, filtration, drying namely get 5-methoxyl group-2-methylthio group-4-diazanyl pyrimidine;
Six, 3-amino-5-methylthio group-8-methoxyl group [1,2,4] triazolos [4,3-c] pyrimidine is synthetic:
5-methoxyl group-2-methylthio group-4-diazanyl pyrimidine of 45.0g is joined in the Virahol of 505ml, again 35.2g cyano group bromine is dissolved in the 100.0g acetonitrile, drip the acetonitrile solution of cyano group bromine, back flow reaction 2.0h is down to room temperature then, reaction solution is poured in the sodium bicarbonate aqueous solution again, stir 1h, white solid is separated out, and filters, 60 ℃ of dryings, namely get 3-amino-5-methylthio group-8-methoxyl group [1,2,4] triazolo [4,3-c] pyrimidine;
Seven, 2-amino-5,8-dimethoxy [1,2,4] triazolos [1,5-c] pyrimidine synthetic:
3-amino-5-methylthio group-8-methoxyl group [1,2,4] triazolo [4 with 30.0g, 3-c] pyrimidine joins in the methanol solution of alkali, adds the 18.4g acrylate, then at 50 ℃ of reaction 8h, reaction solution is lowered the temperature with ice-water bath, stir 1h, filter, 60 ℃ of dryings, namely get 2-amino-5,8-dimethoxy [1,2,4] triazolo [1,5-c] pyrimidine;
Alkali described in the step 1 is sodium methylate, sodium ethylate, sodium hydride, sodium amide, sodium hydroxide or potassium hydroxide;
Alkali described in the step 2 is sodium methylate, sodium ethylate, sodium hydride, sodium amide, sodium hydroxide or potassium hydroxide;
Alkali described in the step 7 is sodium methylate, sodium ethylate, sodium hydride, sodium amide, sodium hydroxide or potassium hydroxide;
Acrylate described in the step 7 is isobornyl acrylate, methyl acrylate, ethyl propenoate, methyl methacrylate, Propenoic acid, 2-methyl, isobutyl ester, methacrylic dodecyl gallate or isobornyl methacrylate.
2. according to the described 2-amino-5 of claim 1, the synthetic method of 8-dimethoxy [1,2,4]-triazolo [1,5-c]-pyrimidine is characterized in that the sodium hydroxide solution described in the step 3 is dissolved in the 620ml water by 32.6g sodium hydroxide to make.
3. according to the described 2-amino-5 of claim 1, the synthetic method of 8-dimethoxy [1,2,4]-triazolo [1,5-c]-pyrimidine is characterized in that sodium bicarbonate aqueous solution described in the step 6 is dissolved in the 500ml water by 32g sodium hydroxide to make.
4. according to the described 2-amino-5 of claim 1, the synthetic method of 8-dimethoxy [1,2,4]-triazolo [1,5-c]-pyrimidine, the methanol solution that it is characterized in that the alkali described in the step 7 is dissolved in 300ml methyl alcohol by the 12.0g sodium methylate and makes.
5. according to claim 1,2,3 or 4 described 2-amino-5, the synthetic method of 8-dimethoxy [1,2,4]-triazolo [1,5-c]-pyrimidine is characterized in that reacting 5h in the step 1 under 11 ℃ condition.
6. according to claim 1,2,3 or 4 described 2-amino-5, the synthetic method of 8-dimethoxy [1,2,4]-triazolo [1,5-c]-pyrimidine is characterized in that reacting 5h in the step 1 under 12 ℃ condition.
7. according to claim 1,2,3 or 4 described 2-amino-5, the synthetic method of 8-dimethoxy [1,2,4]-triazolo [1,5-c]-pyrimidine is characterized in that reacting 5h in the step 1 under 13 ℃ condition.
8. according to claim 1,2,3 or 4 described 2-amino-5, the synthetic method of 8-dimethoxy [1,2,4]-triazolo [1,5-c]-pyrimidine is characterized in that reacting 5h in the step 1 under 15 ℃ condition.
9. according to claim 1,2,3 or 4 described 2-amino-5, the synthetic method of 8-dimethoxy [1,2,4]-triazolo [1,5-c]-pyrimidine is characterized in that reacting 5h in the step 1 under 17 ℃ condition.
10. according to claim 1,2,3 or 4 described 2-amino-5, the synthetic method of 8-dimethoxy [1,2,4]-triazolo [1,5-c]-pyrimidine is characterized in that reacting 5h in the step 1 under 18 ℃ condition.
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| CN104725323A (en) * | 2014-10-16 | 2015-06-24 | 江苏华益科技有限公司 | Synthetic process of 2-methoxyl-4-diazanyl-5-fluoropyrimidine |
| CN105294697A (en) * | 2015-11-20 | 2016-02-03 | 北京英力精化技术发展有限公司 | Synthesis method of 2-amino-5, 8-dimethoxy[1, 2, 4]triazolo[1, 5-c]pyrimidine |
| CN105801492A (en) * | 2014-12-31 | 2016-07-27 | 沈阳中化农药化工研发有限公司 | Preparation method of 2-substituted-4-hydrazino-5-fluoropyrimidine |
| CN110759829A (en) * | 2019-12-10 | 2020-02-07 | 江苏快达农化股份有限公司 | Synthesis method of 3-hydroxy-2-methoxy methyl acrylate sodium salt |
| CN111217817A (en) * | 2020-02-26 | 2020-06-02 | 山东潍坊润丰化工股份有限公司 | Preparation method of triazolopyrimidine herbicide |
| CN111848625A (en) * | 2019-04-24 | 2020-10-30 | 江苏恒瑞医药股份有限公司 | Preparation method and intermediate of heteroaryl [4,3-c ] pyrimidine-5-amine compound |
| CN112730689A (en) * | 2020-12-29 | 2021-04-30 | 营口昌成新材料科技有限公司 | Liquid chromatography analysis method of 2-amino-5, 8-dimethoxy [1,2,4] triazolo [1,5-c ] pyrimidine |
| CN115417875A (en) * | 2022-09-19 | 2022-12-02 | 山东华升新材料有限公司 | Synthesis method of 5,8-dimethoxy- [1,2,4] triazolo [1,5-C ] pyrimidine-2-amine |
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