CN1125038C - Aromatized and acylated amino acid compound and its preparation - Google Patents

Aromatized and acylated amino acid compound and its preparation Download PDF

Info

Publication number
CN1125038C
CN1125038C CN 00125876 CN00125876A CN1125038C CN 1125038 C CN1125038 C CN 1125038C CN 00125876 CN00125876 CN 00125876 CN 00125876 A CN00125876 A CN 00125876A CN 1125038 C CN1125038 C CN 1125038C
Authority
CN
China
Prior art keywords
amino acid
preparation
aromatized
mmole
solvent
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Fee Related
Application number
CN 00125876
Other languages
Chinese (zh)
Other versions
CN1295062A (en
Inventor
衡林森
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Daxian Teachers College
Original Assignee
Daxian Teachers College
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Daxian Teachers College filed Critical Daxian Teachers College
Priority to CN 00125876 priority Critical patent/CN1125038C/en
Publication of CN1295062A publication Critical patent/CN1295062A/en
Application granted granted Critical
Publication of CN1125038C publication Critical patent/CN1125038C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Landscapes

  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Indole Compounds (AREA)

Abstract

The present invention relates to an isoaryl acylated amino acid compound and a preparation method thereof. Isosqurarylium amide, amino acid and alkali react in solvent; amino groups are converted into amino acid salt by the alkali; the amino acid salt and the isosqurarylium amide are treated by amide exchange to prepare isoaryl acylated amino acid salt; then, isoaryl acylated amino acid can be prepared by acidification in acid. The preparation method has the advantages of mild reaction condition, simple and convenient operation, strong applicability and high yield and provides an effective method for preparing a large quantity of isosqurarylium amide compounds containing aryl and amino acid.

Description

Aromatized and acylated amino acid compound and preparation method thereof
Square acid derivative and synthesis technical field thereof in the side's of the invention belongs to acidifying particularly relate to class aromatized and acylated amino acid compound and preparation method thereof.
From successfully synthetic side's acid (Squaric acid such as nineteen fifty-nine Cohen, chemical name 3,4-dihydroxyl-3-cyclobutene-1,2-diketone) since (Cohen, S.et al., J.Am.Chem.Soc., 1959,81,3480), this simple organic molecule that is full of incentive is subjected to chemist's favor always, and its particular structure and abundant reactivity worth are extremely paid attention to, and research is very active both at home and abroad.People not only study its chemical reaction type, and have found that successively its many derivatives have potential and real purposes.In decades, existing thousands of pieces of writing and the relevant bibliographical information of side's acid, wherein major part is a patent documentation, square acidifying has become a vitochemical unique field.Side's acid very easily generates Iso-squaric Amide compound (Zhao Huaming etc., chemical research and application, 1991,3,21 with the aromatic amine reaction; Yuan Deqi etc., organic chemistry, 1992,12,312; Schmidt, A.H., Synthesis, 1980,961).Even and sour the backflow in high boiling solvent with aliphatic amide in side also is difficult to generate corresponding pure Iso-squaric Amide compound (Yuan Deqi etc., organic chemistry, 1992,12,312), fatty group is synthetic for Iso-squaric Amide, existing a small amount of bibliographical information is achieved (Fu Jiasheng etc., organic chemistry, 1993 with round-about way, 5,540; Weighing apparatus Lin Sen etc., Sichuan University's journal (natural science edition), 1997,3,393).
We once reported first carry out the acid amides permutoid reaction of part (50%) by aryl for Iso-squaric Amide and aliphatic amide, synthesized the Iso-squaric Amide compound (weighing apparatus Lin Sen etc., synthetic chemistry, 2000 the 6th phases) that not only contains aryl but also fatty base.Amino acid has extensive, important purposes; in view of characteristics such as the distinctive rigidity of sour four carbocyclic rings in side, aromaticity, stability and shorts of electricity; if the unique texture of general side's acid is incorporated on the amino acid molecular; may make amino acid whose purposes more extensive; particularly if can synthesize and not only contain aryl but also contain amino acid whose Iso-squaric Amide compound; adjustability of structure is bigger like this, more can systematically study the Effect on Performance of substituting group to aromatized and acylated amino acid.Synthesize more useful compound.Consider that amino acid also belongs to aliphatic amide, we are by the method for above-mentioned bibliographical information, aryl is carried out the acid amides permutoid reaction for acid amides and amino acid, all be unrealized through test of many times, yet there are no the report of this compounds and preparation method thereof, this just needs to seek a kind of easy to operate, and the yield height can prepare the method for this compounds in a large number.
The present invention's one class aromatized and acylated amino acid compound, available following general formula: X=halogen in the formula, nitro, C 1-C 4Alkyl, C 1-C 4Alkoxyl group, CH 3CO, H etc.
Y=C 1-C 4Alkyl, phenyl, H etc.
Figure C0012587600042
Figure C0012587600043
CH 2CH (CH 3) 2Deng
The preparation method of the present invention's one class aromatized and acylated amino acid compound; be with Iso-squaric Amide; amino bronsted lowry acids and bases bronsted lowry reacts in solvent; alkali is converted into amino acid salts with amino acid; amino acid salts and Iso-squaric Amide carry out the acid amides permutoid reaction; certainly also can at first amino acid be converted into amino acid salts, add Iso-squaric Amide again and carry out the acid amides permutoid reaction, generate aromatized and acylated amino acid salt with alkali.Separate out the solid aromatized and acylated amino acid with acidifying then, filter, washing, drying, solid product aromatized and acylated amino acid that must be stable, productive rate 70-92%.
The preparation method can represent with following reaction formula: Alkali=NEt 3, NaOH, KOH, Na 2CO 3, K 2CO 3Deng; B=Na +, K +, Deng; The X=halogen, nitro, C 1-C 4Alkyl, C 1-C 4Alkoxyl group, CH 3CO, H etc.; Y=C 1-C 4Alkyl, phenyl, H etc.;
CH 2CH (CH 3) 2Deng;
Z=Cl -, Br -, HSO4 -, H 2PO 4 -, AC -Deng.
Reactant Iso-squaric Amide and amino acid and alkali three's mol ratio is 1: 0.1-10: 0.1-15, and temperature of reaction is 20 ℃-80 ℃, and the reaction times is 1.5-48 hour, and solvent load is every mmole Iso-squaric Amide 10-25ml.
All amino acid all can be used for this reaction, tyrosine for example, and tryptophane, Threonine, phenylalanine, leucine etc., they can be L-type, D-type or DL-type.
The solvent of using in the reaction can be an organic solvent, C 1-C 4Monohydroxy-alcohol (as methyl alcohol, ethanol, propyl alcohol, butanols) acetone, tetrahydrofuran (THF), methylene dichloride, DMF, DMSO etc. or any two kinds mixed organic solvents in them, the mixture of water or described organic solvent and water.
The present invention's one class aromatized and acylated amino acid compound shows through tentative experiment and has been widely used; for example can be applicable to the assorted diels-alder reaction (Hetero Diels-Alder Reaction) of catalysis; the asymmetric thunder husband of catalysis MAERSK reaction (Reformatsky Reaction); can be used for racemic modification alkali for example 1; 2-phenylbenzene thanomin) fractionation; also because of they have antitumor performance, the therefore available preparing anti-tumor medicine that can be used for.
Preparation method's reaction conditions of the present invention is gentle, and easy and simple to handle, suitability is strong, and productive rate is higher, provides an effective means for this synthetic a large amount of classes has not only contained aryl but also contained amino acid whose Iso-squaric Amide compound.
The present invention is further elaborated below in conjunction with embodiment, but do not limit the scope of the invention.
Embodiment 1 preparation 1-(methylphenylamine base)-3-(L-1-benzyl carboxymethylamino) cyclobutene two-2, the two inner salts of 4-glycol
Figure C0012587600061
Get 584mg (2.0 mmole) 1, two (methylphenylamine base) cyclobutenes two-2 of 3-, the two inner salts of 4-glycol, 330mg (2.0 mmole) L-phenylalanine, 112mg (2.0 mmole) KOH, 30ml dehydrated alcohol, reflux stirring reaction 1.5h, solvent evaporated adds less water solid is dissolved, and is acidified to PH=2～3 with dilute hydrochloric acid (1: 1), separate out solid, filter washing, the dry light yellow solid product 645mg that gets.Productive rate 92.0%.
Product: mp167～169 ℃, [α] D 25=-37.0 ° (C=0.5, DMF)
Ultimate analysis C 20H 18N 2O 4Calculated value C 68.58 H 5.18 N 7.99
Measured value C 68.54 H 5.15 N 7.94
IR (pure sample product) 3187,3031,2952,1698,1635,1589,1522,1456,1405,1288,1156,1084,914,762cm -1
1HNMR(DMSO-d 6，400MHz)δ：13.10(S，1H，COOH)，9.67(d1H，J＝9.2Hz，NH)，7.39～7.21(m，10H，10×ArH)，5.02(m，1H，CH)，3.71(S，3H，CH 3)，3.28(ABX，1H， 2J=14.4Hz， 3J＝4.0Hz，PhCH 2)，2.99(ABX，1H， 2J＝14.4Hz， 3J＝11.2Hz，PhCH 2)ppm；
m/z 350(M +)，349(M +-1)。
Embodiment 2 preparation 1-(N-ethyl p-nitrophenyl amido)-3-(D-1-benzyl carboxymethylamino) cyclobutenes two-2, the two inner salts of 4-glycol
Figure C0012587600071
Get 820mg (2.0 mmole) 1, two (the N-ethyl p-nitrophenyl amido) cyclobutenes two-2 of 3-, the two inner salts of 4-glycol, 330mg (2.0 mmole) D-phenylalanine, 80mg (2.0 mmole) NaOH, 35ml 95% ethanol, stirring at room reaction 24h, solvent evaporated adds less water solid is dissolved, filter, filtrate is acidified to PH=2～3 with dilute sulphuric acid (1: 5), separates out yellow solid, filter, washing, dry yellow solid product 695mg, the productive rate 85.0% of getting.
185～187 ℃ of product: mp, [α] D 25=+39.0 ° (C=0.5, DMF)
Ultimate analysis C 21H 19N 3O 6Calculated value C 61.61 H 4.64 N 10.27
Measured value C 61.55 H 4.58 N 10.29
IR (pure sample product) 3155,3014,2961,1688,1644,1578,1510,1466,1410,1260,1102,751cm -1
1H?NMR(DMSO-d 6，400MHz)δ：13.40(S，1H，COOH)，9.98(d，1H，J＝9.4Hz，NH)，8.31～7.22(m，9H，10×ArH)，5.22(m，1H，CH)，3.87(dd，2H，NCH 2)，3.39(ABX，1H， 2J＝14.6Hz， 3J＝4.2Hz，PhCH 2)，3.09(ABX，1H， 2J＝14.6Hz， 3J＝11.3Hz，PhCH 2)，1.32(t，3H，CH 3)ppm；
m/z?409(M +)，408(M +-1)。
Embodiment 3 preparation 1-(N-methyl m-nitro amido)-3-(1-benzyl carboxymethylamino) cyclobutenes two-2, the two inner salts of 4-glycol
Figure C0012587600072
Get 764mg (2.0 mmole) 1, two (the N-methyl m-nitro amido) cyclobutenes two-2 of 3-, the two inner salts of 4-glycol, 660mg (4.0 mmole) DL-phenylalanine, 424mg (4.0 mmole) Na 2CO 3, 50ml methyl alcohol, reflux stirring reaction 2h, solvent evaporated adds the suitable quantity of water dissolved solids, filters, and filtrate is acidified to PH=1～3 with dilute hydrobromic acid (1: 2), separates out solid, filters washing, the dry light yellow solid product 687mg that gets.Productive rate 87.0%.
174～176 ℃ of product: mp,
Ultimate analysis C 20H 17N 3O 6Calculated value C 60.76 H 4.30 N 10.63
Measured value C 60.69 H 4.33 N 10.57
IR (pure sample product) 3160,3025,2930,1690,1638,1570,1520,1455,1408,1278,1130,925,760cm -1
1HNMR(DMSO-d 6，400MHz)δ：13.20(S，1H，COOH)，9.69(d，1H，J＝9.0Hz，NH)，8.20～7.29(m，9H，9×ArH)，5.12(m，1H，CH)，3.75(S，3H，CH 3)，3.31(ABX，1H， 2J＝14.0Hz， 3J＝4.1Hz，PhCH 2)，3.07(ABX，1H， 2J＝14.0Hz， 3J＝11.1Hz，PhCH 2)ppm；
m/z 395(M +)。
Embodiment 4 preparation 1-(N-methyl ortho-nitrophenyl amido)-3-(L-1-is to the hydroxybenzyl carboxymethylamino) cyclobutenes two-2, the two inner salts of 4-glycol
Figure C0012587600081
Get 764mg (2.0 mmole) 1, two (the N-methyl ortho-nitrophenyl amido) cyclobutenes two-2 of 3-, the two inner salts of 4-glycol, 362mg (2.0 mmole) L-tyrosine, 552mg (4.0 mmole) K 2CO 3, the 40ml propyl alcohol, stirring at room is reacted 48h, and solvent evaporated adds the suitable quantity of water dissolved solids, filters, and filtrate extremely no longer produces till the solid with the Glacial acetic acid acidifying, filters washing, the dry yellow solid product 658mg that gets.Productive rate 80.0%.
225～227 ℃ of product: mp, [α] D 25=-3.5 ° (C=0.5, DMF)
Ultimate analysis C 20H 17N 3O 7Calculated value C 58.39 H 4.14 N 10.22
Measured value C 58.26 H 4.10 N 10.13
IR (pure sample product) 3245,1709,1612,1565,1530,1494,1455,1411,1280,1158,981,761cm -1
1HNMR(DMSO-d 6，400MHz)δ：13.19(S，1H，COOH)，9.65(d，1H，J＝9.2Hz，NH)，9.26(S，1H，PhOH)，739～6.65(m，8H，8×ArH)，4.93(m，1H，CH)，3.71(S，3H，CH 3)，3.14(ABX，1H， 2J＝14.0Hz， 3J＝3.6Hz，PhCH 2)，2.86(ABX，1H， 2J＝14.0Hz， 3J＝10.2Hz，PhCH 2)ppm；
m/z 411(M +)，410(M +-1)。
Embodiment 5 preparation 1-hexichol amido-3-(1-is to the hydroxybenzyl carboxymethylamino) cyclobutenes two-2, the two inner salts of 4-glycol
Get 832mg (2.0 mmole) 1,3-pair-pentanoic basic ring butylene two-2, the two inner salts of 4-glycol, 36.2mg (0.2 mmole) DL-tyrosine, 42mg (0.4 mmole) Na 2CO 3, 20ml water, stirring at room reaction 48h filters, and filtrate is acidified to PH=2～3 with concentrated hydrochloric acid, separates out solid, filter, washing, drying gets yellow solid product 60mg, productive rate 70.0%.
185～187 ℃ of product: mp,
Ultimate analysis C 25H 20N 2O 5Calculated value C 70.09 H 4.67 N 6.54
Measured value C 69.92 H 4.71 N 6.48
IR (pure sample product) 3361,1690,1610,1575,1520,1474,1445,1400,1285,1145,980,765cm -1
1HNMR(DMSO-d 6，400MHz)δ：13.25(S，1H，COOH)，9.74(d，1H，J＝9.1Hz，NH)，9.30(S，1H，PhOH)，7.45～6.70(m，14H，14×ArH)，5.05(m，1H，CH)，3.19(ABX，1H， 2J＝14.1Hz， 3J＝3.8Hz，PhCH 2)，2.90(ABX，1H， 2J＝14.1Hz， 3J＝10.4Hz，PhCH 2)ppm；
m/z?428(M +)，427(M +-1)。Embodiment 6 preparation 1-(N-methyl p-Chlorobenzoic acid amide base)-3-(L-1-3 '-the indole methyl carboxymethylamino) cyclobutene two-2, the two inner salts of 4-glycol
Figure C0012587600092
Get 722mg (2.0 mmole) 1, two (N-methyl p-Chlorobenzoic acid amide base) cyclobutene two father-in-law-2 of 3-, the two inner salts of 4-glycol, 408mg (2.0 mmole) L-tryptophane, 112mg (2.0 mmole) KOH, 30ml dehydrated alcohol, reflux stirs 1.5h, and solvent evaporated adds the suitable quantity of water dissolved solids, filter, filtrate is acidified to PH=2～3 with dilute hydrochloric acid (1: 1), separates out light yellow solid, filters, washing, the dry light yellow solid product 728mg that gets.Productive rate 86.0%.
154～156 ℃ of product: mp, [α] D 25=-51.6 ° (C=0.5, DMF)
Ultimate analysis C 22H 18N 3O 4Cl calculated value C 62.34 H 4.25 N 9.92
Measured value C 62.25 H 4.11 N 9.96
IR (pure sample product) 3316,3058,2931,1731,1622,1574,1519,1493,1453,1406,1338,1234,1151,744cm -1
1HNMR(DMSO-d 6，400MHz)δ：13.10(S，1H，COOH)，10.89(S，1H，NH)，9.70(d，1H，J＝8.8Hz，◇-NH)，7.56～6.98(m，9H，9×ArH)，5.05(m，1H，CH)，3.70(S，3H，CH 3)，3.35(ABX，1H， 2J＝14.8Hz， 3J=4.0Hz，ArCH 2)，3.17(ABX，1H， 2J＝14.8Hz， 3J＝10.8Hz，ArCH 2)ppm；
m/z?423(M +)，424(M +-1)。
Embodiment 7 preparation 1-(the N-methyl is to toluidine)-3-(1-3 '-the indole methyl carboxymethylamino) cyclobutene two-2, the two inner salts of 4-glycol
Figure C0012587600101
Get 640mg (2.0 mmole) 1, two (N-methyl para-totuidine base) cyclobutene two father-in-law-2 of 3-, the two inner salts of 4-glycol, 4080mg (20 mmole) DL-tryptophane, 4.17ml (30 mmole) triethylamine, 20ml acetone, the 20ml acetonitrile, stirring at room 24h, solvent evaporated, add the suitable quantity of water dissolved solids, filter, filtrate is transferred PH=2～3 with dilute phosphoric acid (1: 3), separate out solid, filter, washing, dry light yellow solid product 604mg, the productive rate 75.0% of getting.
150～152 ℃ of product: mp,
Ultimate analysis C 23H 21N 3O 4Calculated value C 68.49 H 5.21 N 10.42
Measured value C 68.41 H 5.17 N 10.43
IR (pure sample product) 3341,3108,2901,1702,1601,1544,1520,1480,1447,1403,1318,1214,1140,761cm -1
1HNMR(DMSO-d 6，400MHz)δ：13.02(S，1H，COOH)，10.78(S，1H，NH)，9.60(d，1H，J＝8.6Hz，◇-NH)，7.47～6.77(m，9H，9×ArH)，4.95(m，1H，CH)，3.65(S，3H，NCH 3)，330(ABX，1H， 2J＝14.4Hz， 3J＝4.1Hz，ArCH 2)，3.12(ABX，1H， 2J＝14.4Hz， 3J＝10.5Hz，ArCH 2)，2.28(S，3H，CH 3)ppm；
m/z?403(M +)。
Embodiment 8 preparation 1-(anisidino between the N-methyl)-3-(L-1-1 ' hydroxyethyl-carboxymethyl amino) cyclobutene two-2, the two inner salts of 4-glycol
Get 704mg (2.0 mmole) 1, two (anisidino between the N-methyl) cyclobutenes two-2 of 3-, the two inner salts of 4-glycol, 238mg (2.0 mmole) L-Threonine, 112mg (2.0 mmole) KOH, 20mlDMF, stirring at room reaction 20h, solvent evaporated adds the suitable quantity of water dissolved solids, filter, filtrate is acidified to PH=2～3 with dilute hydrochloric acid (1: 1), separates out solid, filter, washing, dry light yellow solid product 541mg, the productive rate 81% of getting.
213～215 ℃ of product: mp, [α] D 25=+12.2 ° (C=0.5, DMF)
Ultimate analysis C 16H 18N 2O 6Calculated value C 57.49 H 5.39 N 8.38
Measured value C 57.38 H 5.29 N 8.32
IR (pure sample product) 3297,2977,1712,1626,1578,1523,1494,1453,1407,1335,1150,1083,870,761cm -1
1HNMR(DMSO-d 6，400MHz)δ：9.31(d，1H，J＝9.2Hz，NH)，7.47～7.21(m，4H，4×ArH)，4.81(m，1H，CH-COO)，4.19(m，1H，O-CH)，3.76(S，6H，NCH 3，OCH 3)，2.87(S，1H，OH)，1.13(d，3H，J＝6.4Hz，C-CH 3)ppm；
m/z 334(M +)。
Embodiment 9 preparation 1-(adjacent acetylbenzene amido)-3-(1-1 ' hydroxyethyl-carboxymethyl amino) cyclobutene two-2, the two inner salts of 4-glycol
Get 696mg (2.0 mmole) 1, two (the adjacent acetylbenzene amido) cyclobutenes two-2 of 3-, the two inner salts of 4-glycol; 476mg (4.0 mmole) DL-Threonine, 0.33ml (4.0 mmole) pyridine, 25mlDMSO; stirring at room reaction 15h, solvent evaporated adds the suitable quantity of water dissolved solids; filter, filtrate is acidified to PH=2～3 with dilute hydrochloric acid (1: 1), separates out solid; filter; washing, dry light yellow solid product 505mg, the productive rate 76% of getting.
189～191 ℃ of product: mp,
Ultimate analysis C 16H 16N 2O 6Calculated value C 57.83 H 4.82 N 8.43
Measured value C 57.76 H 4.79 N 8.45
IR (pure sample product) 3244,3086,1715,1674,1604,1552,1445,1366,1271,1188,959,829,759cm -1
1HNMR(DMSO-d 6，400MHz)δ：13.05(S，1H，COOH)，10.14(S，1H，NH)，9.40(d，1H，J＝9.3Hz，NH)，8.03～7.25(m，4H，4×ArH)，4.86(m，1H，CH-COO)，4.22(m，1H，O-CH)，2.89(S，1H，OH)，2.54(S，3H，COCH 3)，1.14(d，3H，J＝6.5Hz，C-CH 3)ppm；
m/z 332(M +)，331(M +-1)。
Embodiment 10 preparation 1-(methylphenylamine base)-3-(L-1-2 '-the methyl-propyl carboxymethylamino) cyclobutene two-2, the two inner salts of 4-glycol
Get 584mg (2.0 mmole) 1, two (methylphenylamine base) cyclobutenes two-2 of 3-, the two inner salts of 4-glycol, 262mg (2.0 mmole) L-leucine, 112mg (2.0 mmole) KOH, 20ml tetrahydrofuran (THF), the 20ml methylene dichloride, stirring at room 48h, solvent evaporated, add the suitable quantity of water dissolved solids, be acidified to PH=2～3, separate out solid with dilute sulphuric acid (1: 5), filter, washing, dry light yellow solid product 512mg, the productive rate 81.0% of getting.
Product: mp195～196 ℃, [α] D 25=-93.2 ° (C=0.5, DMF)
Ultimate analysis C 17H 20N 2O 4Calculated value C 64.53 H 6.37 N 8.85
Measured value C 64.45 H 6.29 N 8.81
1HNMR(DMSO-d 6，400MHz)δ：12.97(S，1H，COOH)，9.70(d，1H，J＝10.0Hz，NH)，7.59～721(m，5H，5×ArH)，4.86(m，1H，CH-COO)，3.76(S，3H，NCH 3)，1.76～1.58(m，3H，CH 2CH)，0.89(m，6H，2×CH 3)ppm；
m/z 316(M +)，315(M +-1)。

Claims (6)

1. a class aromatized and acylated amino acid compound is characterized in that this compounds can use following general formula:
Figure C0012587600021
X=halogen in the formula, nitro, C 1-C 4Alkyl, C 1-C 4Alkoxyl group, CH 3CO, H;
Y=C 1-C 4Alkyl, phenyl, H; CH 2CH (CH 3) 2
2. the preparation method of the described class aromatized and acylated amino acid compound of claim 1; it is characterized in that this method is with Iso-squaric Amide; amino bronsted lowry acids and bases bronsted lowry reacts in solvent; generate aromatized and acylated amino acid salt; make with acidifying then, Iso-squaric Amide and amino acid and alkali three's mol ratio is 1: 0.1-10: 0.1-15, and temperature of reaction is 20-80 ℃; reaction times is 1.5-48 hour, and solvent load is every mmole Iso-squaric Amide 10-25ml.
3. by the described preparation method of claim 2, it is characterized in that described amino acid is tyrosine, tryptophane, Threonine, phenylalanine, leucine, they can be the L-types, D-type or DL-type.
4. by the described preparation method of claim 2, it is characterized in that described solvent is organic solvent C 1-C 4The mixture of monohydroxy-alcohol, acetone, tetrahydrofuran (THF), methylene dichloride, DMF, DMSO or their any two kinds mixed organic solvents, water or described organic solvent and water.
5. by the described preparation method of claim 2, it is characterized in that described alkali is NEt 3, NaOH, KOH, Na 2CO 3, K 2CO 3
6. by the described preparation method of claim 2, it is characterized in that described acid is HCl, HBr, H 2SO 4, H 3PO 4, HAc.
CN 00125876 2000-10-27 2000-10-27 Aromatized and acylated amino acid compound and its preparation Expired - Fee Related CN1125038C (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN 00125876 CN1125038C (en) 2000-10-27 2000-10-27 Aromatized and acylated amino acid compound and its preparation

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN 00125876 CN1125038C (en) 2000-10-27 2000-10-27 Aromatized and acylated amino acid compound and its preparation

Publications (2)

Publication Number Publication Date
CN1295062A CN1295062A (en) 2001-05-16
CN1125038C true CN1125038C (en) 2003-10-22

Family

ID=4591658

Family Applications (1)

Application Number Title Priority Date Filing Date
CN 00125876 Expired - Fee Related CN1125038C (en) 2000-10-27 2000-10-27 Aromatized and acylated amino acid compound and its preparation

Country Status (1)

Country Link
CN (1) CN1125038C (en)

Also Published As

Publication number Publication date
CN1295062A (en) 2001-05-16

Similar Documents

Publication Publication Date Title
CN1066713C (en) Stilbene derivatives and pharmaceutical compositions containing them
CN1011784B (en) The method for preparing antianaphylaxis and antibronchospasm of N-dibenzyl-diazacyclo alkyl-alkyl-anilide
EP1705173B1 (en) Binaphthol deratives and their use in optical resolution or optical transformation
CN101062932A (en) Enantioselective process for the preparation of both enantiomers of 10,11-dihydro-10-hydroxy-5h-dibenz [b,f]azepine-5-carboxamide and new crystal forms thereof
CN1125038C (en) Aromatized and acylated amino acid compound and its preparation
CA2083475C (en) Derivatives of ethanolamine, their preparation, and the pharmaceutical compositions containing them
CN1178918C (en) Synthesis of acridine derivative multidrug-resistant inhibitors
JP5176241B2 (en) Dendritic polyamidoamine phthalocyanine derivative
FI113167B (en) Process for the preparation of useful N - [(4,5-dihydroxy- and 4,5,8-trihydroxy-9,10-dihydro-9,10-dioxo-2-anthracenyl) carbonyl] amino acids useful for the treatment of osteoarticular diseases
CN105367478B (en) The preparation process of zafirlukast
CN110684043B (en) C-N axis chiral arylamine compound and preparation method thereof
AU746588B2 (en) Stereoisomeric indole compounds, process for the preparation of the same, and use thereof
CN100349869C (en) Cyanine dye containing end alkynyl radical and its synthesis process
CN101801984A (en) Chiral phosphoramides, chiral N-phosphonimines and methods for forming the same
JPH05503718A (en) Method for dividing optically isomeric hydantoin
CN110511176A (en) Bis- (2- phthalimide) amine and preparation method thereof
CN1827604A (en) Nitro compounds and their application in preparation of pemetrexed
CN1046281C (en) Pharmacologically active enantiomers
CN1107148A (en) Method for the preparation of 2-perflouoroalkyl-3-oxazolin-5-one
CN87100286A (en) Process for preparing dihydropyridine-5-phosphonic acid cyclic propylene ester
CN1169810C (en) Peptide nucleic acid derivatives, intermediate for preparing them and medicinal composition containing them
CN115991678A (en) Diketopiperazine compound, preparation method and application thereof
CN105820062B (en) N (cyclobutenyl of 1 oxo, 4 hydroxyl 2) glycyl amines and its preparation method and application
CN1176074C (en) Multi-substitutent beta-monofluoropyrrole compounds and preparing process thereof
CN1030229A (en) Butenoic acid amides and their salt and comprise their medical component and preparation method thereof

Legal Events

Date Code Title Description
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C06 Publication
PB01 Publication
C14 Grant of patent or utility model
GR01 Patent grant
C19 Lapse of patent right due to non-payment of the annual fee
CF01 Termination of patent right due to non-payment of annual fee