CN102250126A - Dipurine derivative and synthesis thereof - Google Patents

Dipurine derivative and synthesis thereof Download PDF

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Publication number
CN102250126A
CN102250126A CN201010174989XA CN201010174989A CN102250126A CN 102250126 A CN102250126 A CN 102250126A CN 201010174989X A CN201010174989X A CN 201010174989XA CN 201010174989 A CN201010174989 A CN 201010174989A CN 102250126 A CN102250126 A CN 102250126A
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Prior art keywords
purine
chloro
amine
necked flask
derivative
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汪中明
孔睿睿
韩克飞
朱红
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Beijing University of Chemical Technology
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Beijing University of Chemical Technology
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Abstract

The invention relates to compounds of a formula (I) and synthesis thereof. In the formula, m, n and p are defined in the description. The dipurine derivatives are connected with two 6-chloropurine and have a symmetric structure. Dipurine derivatives and metal complexes are widely used in materials such as electroluminescent materials, molecular switches, molecular shuttles, nano wires and the like.

Description

A kind of pair of purine analog derivative and synthetic
Technical field
The invention belongs to the organic synthesis field, be specifically related to the compound of a class novelty, particularly the two purine derivatives of a class and synthetic.
Background technology
In recent years, along with science and technology development, the purine derivative metal complexes is subjected to people's attention in the applied research aspect the materials such as electroluminescent, molecular switch, molecule shuttle, nm-class conducting wire.
U.S. Pat 4,565 in 1986, and 868 disclose a class guanine 9 bit derivants, and 9 are connected with the ether oxygen groups that contains side chain.But this compound has only a guanine to carry out 9 replacements.
Nineteen ninety, U.S. Pat 4,916,225 disclosed guanine 9 bit derivants, 9 ether oxygen groups that are connected with straight chain.But also have only a guanine to carry out 9 replacements.
U.S. Pat 5,565 in 1996, and 461 disclose purine 9 bit derivants, and 9 are connected with alkyl group, also had only a guanine to carry out 9 replacements.
Before present patent application work, still there be not the patent documentation or the scientific paper report of this pair purine derivative aspect.
Summary of the invention
The invention provides two purine derivatives of formula I
Wherein m is 2,3,4,5,6,7, or 8, n and p are 2 or 3, and n 〉=p.
Preferably, described purine derivative is:
9,9 '-(1,4-diazacyclo hexyl-1, two (ethyl)-2 of 4-, 2 ')-two-(6-chloro-9H-purine-2-amine).
9,9 '-(1,4-diazacyclo hexyl-1, two (propyl group)-3 of 4-, 3 ')-two-(6-chloro-9H-purine-2-amine).
9,9 '-(1,4-diazacyclo hexyl-1, two (butyl)-4 of 4-, 4 ')-two-(6-chloro-9H-purine-2-amine).
9,9 '-(1,4-diazacyclo heptyl-1, two (ethyl)-2 of 4-, 2 ')-two-(6-chloro-9H-purine-2-amine).
9,9 '-(1,4-diazacyclo heptyl-1, two (propyl group)-3 of 4-, 3 ')-two-(6-chloro-9H-purine-2-amine).
9,9 '-(1,4-diazacyclo heptyl-1, two (butyl)-4 of 4-, 4 ')-two-(6-chloro-9H-purine-2-amine).
9,9 '-(1,4-diazacyclo octyl group-1, two (ethyl)-2 of 5-, 2 ')-two-(6-chloro-9H-purine-2-amine).
9,9 '-(1,4-diazacyclo octyl group-1, two (propyl group)-3 of 5-, 3 ')-two-(6-chloro-9H-purine-2-amine).
9,9 '-(1,4-diazacyclo octyl group-1, two (butyl)-4 of 5-, 4 ')-two-(6-chloro-9H-purine-2-amine).
Embodiment:
The specific embodiment of the invention is not limited to following embodiment.Embodiments of the invention can make the professional and technical personnel more fully understand the present invention.
Embodiment one:
1) 2-amino-6-chloro-9-bromopropyl purine is synthetic
With 1, (16.2g, 80mmol), (3.4g, 20mmol), (8.28g 60mmol) joins in the there-necked flask salt of wormwood 2-amino-6-chlorine guanine the 3-dibromopropane, and logical nitrogen stirring at normal temperature is reacted, and the TLC monitoring reaction carries out degree respectively.Suction filtration, decompression is spin-dried for SiO behind the solvent 2(ethyl acetate: sherwood oil 4: 1) purifying obtains white solid 2-amino-6-chloro-9-bromopropyl purine in the column chromatography separation.
2) N, N '-1,4-diaza-cyclohexane synthetic
(4.5g, 0.045mmol), 6ml water mixes quadrol, slowly drips 10%NaOH solution 35ml under the stirring at room, adds in batches simultaneously that (1h dropwises for 31.5g, 0.165mol) TsCl.Continue reaction 4h, placement is spent the night.White solid water that filtration is separated out and saturated NaHCO 3Wash to PH=8, vacuum-drying, crude product is through ethyl alcohol recrystallization.Obtain white solid N, N '-1,4-two p-toluenesulfonyl quadrol 15.45g.
With the 50ml dry DMF, and NaH (6.5g, 0.16mol); N, (15g 0.04mol) places the 250ml there-necked flask to N '-two p-toluenesulfonyl quadrol; slowly be warming up to 50-60 ℃ of reaction 30min down, splash into glycol dibromide (7.51g; 0.04mol), continue to add 12h, after finishing, reaction is chilled to room temperature; reaction solution is poured in the 50ml frozen water; separate out white solid, filter, and use saturated Na 2CO 3Washing is dry, and recrystallization obtains product N, N '-1,4-two p-toluenesulfonyl piperidine 12.47g.
With N, N '-1,4-two p-toluenesulfonyl piperidines (4.11g, 10mmol), 40%HBr, Glacial acetic acid, each 50ml mixing backflow 4h of phenol, evaporated under reduced pressure obtains red jelly.Add 25ml acetone, separate out solid, filter, filter cake is washed till white with acetone.This solid is dissolved with less water, be neutralized into weakly alkaline with ammoniacal liquor then, ethyl acetate (50ml * 3) extraction, anhydrous Na 2SO 4Drying steams solvent and obtains N, N '-1, and 4-piperidine crude product, 73-75 ℃/3.98kPa cut is collected in underpressure distillation, and room temperature is placed, and solidifies crystallization and gets N, N '-1,4-piperidine 0.70g.
3) formula (I) compound is synthetic
(2.00g, 10mmol), (1.00g 8mmol) is dissolved in the 10ml dry DMF salt of wormwood, and places the 100ml there-necked flask with 2-amino-6-chloro-9-bromopropyl purine.To be dissolved in the N among the dry DMF of 10ml then, N '-1, the 4-piperidine (0.34g 4mmol) is added drop-wise in the there-necked flask, under the nitrogen protection, and stirring at normal temperature 20h.Solids removed by filtration, be spin-dried for solvent after, column chromatography is separated (ethyl acetate: methyl alcohol=1: 1), obtain target product.Fusing point: 238-242 ℃.IR (KBr compressing tablet) v/cm-1 3427.9 (N (CH 2) 3); 3323.1 (NH); 3199.9 (NCH 2); 1HNMR (600MHz, DMSO) δ 8.079 (s, 2H, NHN); δ 6.851 (s, 2H ,-NH 2) δ 4.038-4.061 (t, J=13.8,4H ,-CH 2-); δ 2.199-2.221 (t, J=13.2,4H ,-CH 2-) δ 2.210 (br, 8H ,-CH 2-) δ 1.895-1.918 (t, J=13.8,4H ,-CH 2-) .ES MS:m/z calcd for[M+H] +505.4 found 505.4.
Embodiment two:
1) according to embodiment 1) method carry out.
2) according to embodiment 1) method carry out.
3) (2.00g, 10mmol), (1.00g 8mmol) is dissolved in the 10ml dry DMF salt of wormwood, and places the 100ml there-necked flask with 2-amino-6-chloro-9-bromopropyl purine.To be dissolved in the N among the dry DMF of 10ml then, N '-1, the 4-piperidine (0.34g 4mmol) is added drop-wise in the there-necked flask, under the nitrogen protection, and stirring at normal temperature 30h.Solids removed by filtration, be spin-dried for solvent after, column chromatography is separated (ethyl acetate: methyl alcohol=1: 1), obtain target product.Fusing point: 238-242 ℃.IR (KBr compressing tablet) v/cm -13427.9 (N (CH 2) 3); 3323.1 (NH); 3199.9 (NCH 2); 1HNMR (600MHz, DMSO) δ 8.079 (s, 2H, NHN); δ 6.851 (s, 2H ,-NH 2) δ 4.038-4.061 (t, J=13.8,4H ,-CH 2-); δ 2.199-2.221 (t, J=13.2,4H ,-CH 2-) δ 2.210 (br, 8H ,-CH 2-) δ 1.895-1.918 (t, J=13.8,4H ,-CH 2-) .ES MS:m/zcalcd for[M+H]+505.4, found 505.4.
Embodiment three:
1) according to embodiment 1) method carry out.
2) according to embodiment 1) method carry out.
3) (2.00g, 10mmol), (4.12g 8mmol) is dissolved in the 10ml dry DMF ethyl diisopropyl amine, and places the 100ml there-necked flask with 2-amino-6-chloro-9-bromopropyl purine.To be dissolved in the N among the dry DMF of 10ml then, N '-1, the 4-piperidine (0.34g 4mmol) is added drop-wise in the there-necked flask, under the nitrogen protection, and stirring at normal temperature 20h.Solids removed by filtration, be spin-dried for solvent after, column chromatography is separated (ethyl acetate: methyl alcohol=1: 1), obtain target product.Fusing point: 238-242 ℃.IR (KBr compressing tablet) v/cm-1 3427.9 (N (CH 2) 3); 3323.1 (NH); 3199.9 (NCH 2); 1HNMR (600MHz, DMSO) δ 8.079 (s, 2H, NHN); δ 6.851 (s, 2H ,-NH 2) δ 4.038-4.061 (t, J=13.8,4H ,-CH 2-); δ 2.199-2.221 (t, J=13.2,4H ,-CH 2-) δ 2.210 (br, 8H ,-CH 2-) δ 1.895-1.918 (t, J=13.8,4H ,-CH 2-) .ES MS:m/z calcdfor[M+H]+505.4, found 505.4.
Embodiment four:
1) according to embodiment 1) method carry out.
2) according to embodiment 1) method carry out.With glycol dibromide, change 1 into, the 3-dibromopropane obtains N, N '-1,4-azepan.
3) (2.00g, 10mmol), (1.00g 8mmol) is dissolved in the 10ml dry DMF salt of wormwood, and places the 100ml there-necked flask with 2-amino-6-chloro-9-bromopropyl purine.To be dissolved in the N among the dry DMF of 10ml then, N '-1, the 4-azepan (0.40g 4mmol) is added drop-wise in the there-necked flask, under the nitrogen protection, and stirring at normal temperature 20h.Solids removed by filtration, be spin-dried for solvent after, column chromatography is separated (ethyl acetate: methyl alcohol=1: 1), obtain target product.Fusing point: 220-222 ℃..ES?MS：m/z?calcd?for[M+H] +519.3，found519.4。
Embodiment five:
1) according to embodiment 4 1) method carries out;
2) according to embodiment 4 2) method carries out;
3) (2.00g, 10mmol), (4.12g 8mmol) is dissolved in the 10ml dry DMF ethyl diisopropyl amine, and places the 100ml there-necked flask with 2-amino-6-chloro-9-bromopropyl purine.To be dissolved in the N among the dry DMF of 10ml then, N '-1, (0.40g 4mmol) is added drop-wise in the there-necked flask 4-azepan, and under the nitrogen protection, 40 ℃ are stirred 20h.Solids removed by filtration, be spin-dried for solvent after, column chromatography is separated (ethyl acetate: methyl alcohol=1: 1), obtain target product.Fusing point: 220-222 ℃.ES?MS：m/z?calcd?for[M+H] +519.4，found?519.4。
Embodiment six:
4) according to embodiment 4 1) method carries out;
5) according to embodiment 4 2) method carries out;
3) (2.00g, 10mmol), (1.00g 8mmol) is dissolved in the 10ml dry DMF salt of wormwood, and places the 100ml there-necked flask with 2-amino-6-chloro-9-bromopropyl purine.To be dissolved in the N among the dry DMF of 10ml then, N '-1, the 4-azepan (0.40g 4mmol) is added drop-wise in the there-necked flask, under the nitrogen protection, and stirring at normal temperature 30h.Solids removed by filtration, be spin-dried for solvent after, column chromatography is separated (ethyl acetate: methyl alcohol=2: 1), obtain target product.Fusing point: 220-222 ℃..ES?MS：m/z?calcd?for[M+H] +519.4，found519.4。

Claims (4)

1. the two purine derivatives of a class is characterized in that having formula (I) structure
Wherein m is 2,3,4,5,6,7, or 8, n and p are 2 or 3, and n 〉=p.
2. pair purine derivative as claimed in claim 1 is characterized in that described compound (I) is: 9,9 '-(1,4-diazacyclo hexyl-1, two (the alkyl)-m of 4-, m ')-two-(6-chloro-9H-purine-2-amine).N is 2; P is 2; M is 2,3,4,5,6,7, or 8;
3. pair purine derivative as claimed in claim 1 is characterized in that described compound (I) is 9,9 '-(1,4-diazacyclo heptyl-1, two (the alkyl)-m of 4-, m ')-two-(6-chloro-9H-purine-2-amine).N is 3; P is 2; M is 2,3,4,5,6,7, or 8;
4. pair purine derivative as claimed in claim 1 is characterized in that described compound (I) is: 9,9 '-(1,4-diazacyclo octyl group-1, two (the alkyl)-m of 5-, m ')-two-(6-chloro-9H-purine-2-amine).N is 3; P is 3; M is 2,3,4,5,6,7, or 8.
CN201010174989XA 2010-05-18 2010-05-18 Dipurine derivative and synthesis thereof Pending CN102250126A (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103360330A (en) * 2013-08-07 2013-10-23 刘怀振 Synthetic method for homopiperazine
CN104744382A (en) * 2015-02-12 2015-07-01 渭南畅通药化科技有限公司 Preparation method of homopiperzine

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4565868A (en) * 1983-02-07 1986-01-21 Syntex (U.S.A.) Inc. Process for preparing guanine derivatives
EP0290630A1 (en) * 1986-11-25 1988-11-17 Institut Organicheskogo Sinteza Akademii Nauk Latviiskoi Ssr 9-substituted guanines
EP0343133A1 (en) * 1988-05-06 1989-11-23 Medivir Aktiebolag Derivatives of purine, process for their preparation and a pharmaceutical preparation
CN101602765A (en) * 2009-05-13 2009-12-16 北京化工大学 6-alkylamino-2-alkylthio-9-contains ester alkyl purine derivative and synthetic method thereof
CN102250094A (en) * 2010-05-18 2011-11-23 北京化工大学 2-alkylthio-9-alcoxyalkyl adenine compound and synthesis thereof

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4565868A (en) * 1983-02-07 1986-01-21 Syntex (U.S.A.) Inc. Process for preparing guanine derivatives
EP0290630A1 (en) * 1986-11-25 1988-11-17 Institut Organicheskogo Sinteza Akademii Nauk Latviiskoi Ssr 9-substituted guanines
EP0343133A1 (en) * 1988-05-06 1989-11-23 Medivir Aktiebolag Derivatives of purine, process for their preparation and a pharmaceutical preparation
CN101602765A (en) * 2009-05-13 2009-12-16 北京化工大学 6-alkylamino-2-alkylthio-9-contains ester alkyl purine derivative and synthetic method thereof
CN102250094A (en) * 2010-05-18 2011-11-23 北京化工大学 2-alkylthio-9-alcoxyalkyl adenine compound and synthesis thereof

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Title
RAY LUO,等: "The Physical Basis of Nucleic Acid Base Stacking in Water", 《BIOPHYSICAL JOURNAL》 *
TOSHIO ITAHARA, 等: "Molecular assemblies of bis- and tris-adenine derivatives", 《JOURNAL OF MOLECULAR STRUCTURE》 *
TOSHIO ITAHARA,等: "Role of Nitrogen Atom in Aromatic Stacking", 《J. PHYS. CHEM. B》 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103360330A (en) * 2013-08-07 2013-10-23 刘怀振 Synthetic method for homopiperazine
CN104744382A (en) * 2015-02-12 2015-07-01 渭南畅通药化科技有限公司 Preparation method of homopiperzine

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Application publication date: 20111123