KR870000449B1 - Process for preparing aminoalkyl furan derivatives - Google Patents

Abstract

Aminoalkyl furan derivs. (I) and their salts are new. (I) are prepd. by reacting a nitroethene deriv. of formula H2NC(NHCH3)= CHNO2 with (II) in the presence of tetralkyl ammonium sulfurous salt, tetralkyl ammonium hydrogen salt, trialkyl benzene ammonium halogen salt as an inter-phase-moving catalyst at 20-50≰C. Prepg. furan derivs. (I) are useful for treatment of gastric ulcer and dyspepsia. (I) can be obtd. by isolated salts or stable acid addn. salts.

Description

Method for preparing amino alkylfuran derivative

The present invention relates to amino alkylfuran derivatives of formula (I) and salts thereof which are known to be effective therapeutic agents for gastric ulcers and peptic ulcers.

The compound of formula (I) is a known compound, the conventional preparation methods are US Patent No. 4,128,658, UK Patent No. 1,565,966, 2,075,980, German Patent No. 2,734,070, European Patent No. 59,082, 55,625, 64,869 It is published in the issue.

Conventional manufacturing methods disclosed in these various documents are generally as follows.

First, the intermediate compound of formula (III) is prepared and separated by reacting cystiamine hydrochloride from furanmethanol derivative of formula (II), and then reacts with nitroethene derivative of formula (V) or bis of formula (IV). There is a method of preparing a compound of formula (I) by reacting a methylthio compound and methylamine in turn,

Second, a thiazolidine derivative of formula (VI) was prepared from bismethylthio compound of formula (IV) and a cystiamine hydrochloride, and then reacted with methylamine to prepare an intermediate compound of formula (VII). There is a method of preparing a compound of formula (I) by reacting a furanmethanol derivative of

Third, there is a method of preparing the target compound of formula (I) by reacting aziridine or 2-chloroethylamine with a nitroethene derivative of formula (V) followed by reaction with a thiol derivative of formula (VII),

As with other similar reaction pathways or via the same intermediate compounds, these conventional preparation methods use expensive cystiamine hydrochloride to make them less economical or to lower the yield of each process, or they can be used in practical applications such as aziridine or derivatives thereof. There are many disadvantages, such as the use of compounds that are difficult to apply to industrial production.

The present invention provides an advanced method of preparation via a novel concept of intermediate compounds via an entirely new synthetic route, using compounds that are much cheaper than known methods.

The present invention will be described in more detail as follows.

2-[[[[5- (dimethylamino) methyl-2-furanyl] methyl] of Structural Formula (VII) produced using thioglycol from the furanmethanol derivative of Structural Formula (II) or the halogen compound of Structural Formula (VII) A new intermediate compound of formula (VII) is prepared by reacting thio] ethanol with a halogenating reagent such as thionyl chloride, phosphorus tribromide, potassium iodide, or p-toluene sulfonyl chloride.

The reaction of Structural Formula (I), which is an intermediate compound chemically activated, with 1-amino-1-methylamino-2-nitroethene of Structural Formula (XII) Amino alkylfuran derivatives and salts thereof are prepared in high yields.

The characteristic synthetic route of the present invention is represented by the following chemical reaction formula.

First, the reaction for preparing a compound of formula (VII) using thioglycol from the furanmethanol derivative of formula (II) is carried out in the presence of an inorganic acid such as hydrochloric acid, usually with water as a solvent, in a temperature range of 20 ° -50 ° C. It is almost complete in time.

Furthermore, the compound of structural formula (VII) can be manufactured through the compound of structural formula (VII). The halogen compound of formula (II) can be easily prepared from the formula (II) using thionyl chloride, hydrobromic acid, etc., and is usually separated into stable acid addition salts such as hydrochloride.

The reaction for preparing the compound of formula (IV) using thioglycol from the acid addition salt of formula (IV) proceeds almost quantitatively in 1 hour to 5 hours at 0 ° C to room temperature in water, alcohol or a mixed solvent thereof. The reaction is preferably used in the amount of 1 to 2 equivalents of inorganic bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate and the like. The intermediate compound of the structural formula (IV) may be separated into an oily liquid or acid addition salts such as hydrochloride and oxalate.

The following is one of the characteristic steps of the present invention. From the compound of the structural formula (IV), chemical activity is reduced using halogenated reagents such as thionyl chloride, phosphorus tribromide, potassium iodide, p-toluene sulfonyl chloride, and the like. A new intermediate compound of formula (VII) is prepared that contains a strong separator.

The reaction for preparing a halogen compound of the formula (VII) ac from the formula (III) proceeds generally well in a general organic solvent other than water or alcohol using the above-mentioned halogenation reagent, and especially carbon tetrachloride, chloroform, dichloromethane, etc. More preferred are solvents of halogenated hydrocarbons. These reactions are possible even under mildly acidic or neutral conditions, and organic bases such as triethylamine may be used.

The brominated compound of the structural formula (VIII-b) and the iodide compound of the structural formula (VIII-c) can also be easily converted from the chloride of the structural formula (VIII-a) by using calcium bromide or sodium iodide. At this time, the reaction can be proceeded almost quantitatively using a phase bipolar catalyst (PTC) such as trialkylbenzyl ammonium halogen salt, tetraalkylammonium halogen salt and tetraalkylammonium sulfite.

Compounds of formula (I)-(d) are prepared from formula (III) and p-toluene sulfonyl chloride, where non-polar organic solvents such as benzene are mixed with water to give general properties such as trialkyl benzyl ammonium halide salts and tetraalkyl ammonium halide salts. The desired compound can be obtained in high yield in the presence of a phase transfer catalyst. The reaction proceeds quantitatively within 2 to 4 hours in the temperature range of 0 ° -40 ° C in the presence of inorganic bases such as sodium hydroxide, potassium hydroxide and the like.

The following is the final step of preparing the final target compound of formula (I) by reacting the nitroethene derivative of formula (XII) from the intermediate compound of formula (VII); Manufacturing method.

The reaction for preparing Structural Formula (I) from a halogen compound of Structural Formula (VII) and a compound of Structural Formula (XII) is carried out on a nonpolar organic solvent which is not mixed with water such as benzene, toluene, chloroform, dichloromethane and carbon tetrachloride. After dissolving the halogen compound of ac), the nitroethene derivative of the structural formula (XII) is dissolved in an aqueous solution containing inorganic bases such as sodium hydroxide and potassium hydroxide, and then the two layers are mixed with each other to proceed with the reaction. At this time, a desired reaction may be selectively performed by using a general phase transfer catalyst such as tetraalkyl ammonium sulfite, tetra alkylammonium halogen salt, trialkylbenzyl ammonium halogen salt and the like. In addition, it is also possible to react in the presence of the above-described phase transfer catalyst and the inorganic base using only an organic solvent containing no mole.

The reaction for preparing Structural Formula (I) from the compound of Structural Formula (VII-d) and the compound of Structural Formula (XII) includes water, methanol, ethanol, 2-propanol, N, N-dimethylformamide, dimethylsulfoxide, acetonitrile and the like. In solvents of the same polarity or mixed solvents thereof, they proceed well in the presence of inorganic bases such as sodium hydroxide and potassium hydroxide and tertiary bases such as triethylamine, and are completed within 24 hours in the temperature range of 25 ° -85 ° C.

Structural formula (I) obtained by the new manufacturing method of this invention may be isolate | separated in the form of free base, and can also be isolate | separated into stable acid addition salts, such as hydrochloride, using a conventional method.

The 1-amino-1-methylamino-2-nitroethene of the structural formula (XII) used in the characteristic synthetic route of the present invention can be easily prepared by using ammonia from the known compound of the structural formula (V).

This reaction is carried out within 5 to 15 hours in a temperature range of 20 ° -60 ° C. in a solvent containing water, a hydroxyl group such as methanol, ethanol, 2-propanol, or a polar organic solvent mixed with water or a mixed solvent thereof. Proceed quantitatively.

As described in detail above, the present invention is to prepare an intermediate compound of the formula (VII), which is activated from the compound of the formula (VII), and react with a compound of the formula (VII) to prepare the target compound of the formula (I). The use of inexpensive and convenient reagents in conventional synthetic routes all improves the disadvantages of conventional methods, the use of expensive reagents, low yields, industrial difficulties, and the like, to provide new manufacturing methods that are technologically and economically advanced.

The starting material of formula (II) or (iii) is a known material and is obtained by the method of British Patent No. 2075980.

In order to better understand the production method of the present invention, the following examples will be described.

Example 1

2-[[[5- (dimethylamino) methyl-2-furanyl] methyl] thio] ethanol

46.5 g of 5- (dimethylamino) methyl-2-furanmethanol is dissolved in 220 ml of concentrated hydrochloric acid, and 24.6 g of thio glycol is added dropwise for 2 hours while maintaining the temperature at 5 DEG C or lower while cooling. The reaction solution was stirred at 25 ° -35 ° C. for 20 hours, cooled to 10 ° C. or lower, and 5N aqueous sodium hydroxide solution was added to adjust the pH to 10.0-10.2. After further stirring for 30 minutes, the extract was extracted once with 20 ml of chloroform and twice with 100 ml at 10 캜 or lower. After activated carbon treatment, the mixture was concentrated under reduced pressure at 20 ° C. or lower, the residue was dissolved in 90 ml of acetone, and left at 5 ° C. or lower for 2 hours. The filtrate was concentrated under reduced pressure to give 50.3 g of the title compound.

Boiling Point: 135 ℃ (0.5mmHg)

TLC: (silica gel / chloroform: 2-propanol: 25% aqueous ammonia = 10: 10: 1), Rf = 0.66

Elemental analysis: C ₁₀ H ₁₇ NO ₂ S (215.31)

Theoretic value (%): C 55.78, H 7.96, N 6.51

Found (%): C 55.80, H 7.90, N 6.58

Example 2

2-[[[5- (dimethylamino) methyl-2-furanyl] methyl] thio] ethanol

(a) 84 g of hydrochloride (1: 1) of [5- (dimethylamino) methyl-2-furanyl] methyl chloride was dissolved in 320 ml of methanol, cooled to 0 ° C., and then a solution of 31.3 g of thioglycol in 80 ml of methanol was gradually dissolved. Add. 480 ml of a 10% methanol solution of potassium hydroxide was added dropwise for 3 hours while maintaining 0 ° -5 ° C. The temperature is gradually raised, and the mixture is further stirred at 20 ° -25 ° C. for 1 hour, and distilled under reduced pressure at 40 ° C. or lower to recover methanol. 200 ml of water was added to the mixture of the solid and liquid, followed by extraction with dichloromethane. Post-reaction treatment was carried out in the same manner as in Example 1 to obtain 72.3 g of the same title compound.

Elemental analysis: C ₁₀ H ₁₇ NO ₂ S (215.31)

Theoretic value (%): C 55.78, H 7.96, N 6.51

Found (%): C 55.80, H 7.88, N 6.54

(b) Using hydrobromic acid hydrochloride (1: 1) of [5- (dimethylamino) methyl-2-furanyl] methyl bromide as a starting material and reacting in the same manner as in (a), the same title compound is 89%. To yield.

Example 3

Hydrochloride (1: 1) of 2-[[[5- (dimethylamino) methyl-2-furanyl] methyl] thio] ethyl chloride

43 g of 2-[[[5- (dimethylamino) methyl-2-furanyl] methyl] thio] ethanol obtained in Examples 1 and 2 were dissolved in 250 ml of chloroform, and 140 ml of chloroform solution containing 72 g of thionyl chloride was dissolved in 30 ml. It is dripped for 2 hours in the range of -50 degreeC. After further stirring at room temperature for 3 hours, 200 ml of anhydrous ethanol was added and heated to 50 ° -60 ° C. for 1 hour. 2.5 g of activated carbon was added, and the filtrate obtained by filtration at 50 ° C was concentrated under reduced pressure. The residue was dissolved in 120 ml of 2-propanol, treated with activated charcoal at room temperature and concentrated. After dissolving again in 80 ml of acetone and left for more than 2 hours at 5 ℃ or less a small amount of insoluble impurities are produced. Filtration and concentration under reduced pressure gave 48.6 g of pure title compound.

Elemental analysis: C ₁₀ H ₁₆ ClNOS.HCl (270.22)

Theoretic value (%): C 44.45, H 6.34, N 5.18

Found (%): C 44.41, H 6.45, N 5.20

TLC: (silica gel / chloroform: 2-propanol: 25% ammonia water = 10: 10: 1), Rf = 0.83

Example 4

2-[[[5- (dimethylamino) methyl-2-furanyl] methyl] thio] ethyl bromide

After dissolving 21.5 g of 2-[[[5- (dimethylamino) methyl-2-furanyl] methyl] thio] ethanol obtained in Examples 1 and 2 in 60 ml of carbon tetrachloride, 30 ml of carbon tetrachloride solution containing 8.7 g of phosphorus tribromide Slowly dropwise for 2 hours. The exotherm causes the temperature to be between mild reflux at room temperature. It was further refluxed for 30 minutes and then concentrated under reduced pressure. The residue was dissolved in 120 ml of dichloromethane and washed twice with 30 ml of 10% aqueous sodium hydrogen carbonate solution and twice with 30 ml of 10% aqueous sodium chloride solution at 15 ° C. or lower. The organic layer was filtered with magnesium sulfate and activated carbon at room temperature, and concentrated under reduced pressure. This gives 24.2 g of the title compound.

Elemental analysis: C ₁₀ H ₁₆ BrNOS (278.21)

Theoretic value (%): C 43.17, H 5.80, N 5.03

Found (%): C 43.13, H 5.84, N 4.98

Example 5

2-[[[5- (dimethylamino) methyl-2-furanyl] methyl] thio] ethyl iodine

After mixing 32.5 g of OH and 115.5 g (67.5 ml) of 85% phosphoric acid, the mixture was stirred for a while, and then 166 g of potassium iodide was added at 25 ° C. or lower. After 10 minutes, 2-[[[5- (dimethylamino) methyl-2-furanyl was added. 53.75 g of methyl] thio] ethanol are added slowly. After heating little by little and reacted at 80 ° -90 ° C for 4 hours, it is cooled to room temperature. 75 ml of distilled water and 125 ml of ether were added, the mixture was stirred vigorously for 20 minutes and the ether layer was separated. Shake vigorously with 25 ml of a 10% aqueous solution of sodium thiosulfate, wash twice with 100 ml of saturated aqueous sodium chloride solution, and then dry over magnesium sulfate. The solvent is concentrated under reduced pressure to obtain 68.3 g of the title compound.

Elemental Analysis: C ₁₀ H ₁₆ INOS (325.21)

Theoretic value (%): C 36.93, H 4.96, N 4.31

Found (%): C 36.88, H 4.99, N 4.25

Example 6

2-[[[5- (dimethylamino) methyl-2-furanyl] methyl] thio] ethyl iodine

27 g of a hydrochloride (1: 1) of 2-[[[5- (dimethylamino) methyl-2-furanyl] methyl] thio] ethyl chloride obtained in Example 3 was dissolved in 130 ml of distilled water, followed by sodium hydroxide 5N at 20 캜 or lower. 20 ml of aqueous solution was added, stirred for a while, and then extracted three times with 50 ml of chloroform. The combined extracts were washed with 40 ml of saturated aqueous sodium chloride solution, dried over sodium sulfate and concentrated under reduced pressure to obtain 23.2 g of an oily residue.

The mixture of 22.5 g of sodium iodide and 150 ml of methyl ethyl ketone was heated to 50 ° -60 ° C. for 1 hour, and then 23.2 g of the intermediate compound obtained by the operation of was added and refluxed for 20 hours. The inorganic salt formed by cooling to room temperature was filtered and removed, and the filtrate was extracted by adding 60 ml of distilled water and 120 ml of ether to the residue obtained by concentrating under reduced pressure. The organic layer was separated and treated in the same manner as in Example 5 to obtain 29.6 g of the same title compound.

Example 7

2-[[[5- (dimethylamino) methyl-2-furanyl] methyl] thio] ethyl bromide

Hydrochloric acid was removed using 54 g of hydrochloride (1: 1) of 2-[[[5- (dimethylamino) methyl-2-furanyl] methyl] thio] ethyl chloride obtained in Example 3 according to the first half treatment method of Example 6. Separated by free chloro compound (46.4g) and dissolved in 220ml of benzene.

180 ml of an aqueous solution of 21.06 g of 95% calcium bromide and 1.74 g of tetrahexyl ammonium bromide are mixed together with the benzene layer. The mixture was refluxed for 24 hours, cooled to room temperature, the organic layer was separated, washed three times with 50 ml of saturated aqueous sodium chloride solution, dried over magnesium sulfate, and treated with activated carbon at room temperature. The solvent was concentrated under reduced pressure, the residue was dissolved in 80 ml of acetone, and the mixture was left at 5 ° C. or less for 2 hours. Then, a small amount of the insoluble material was filtered off and concentrated under reduced pressure to obtain 52.2 g of the same title compound as in Example 4.

Example 8

2-[[[5- (dimethylamino) methyl-2-furanyl] methyl] thio] ethyl D-toluene sulfonate

21.5 g of 2-[[[5- (dimethylamino) methyl-2-furanyl] methyl] thio] ethanol was dissolved in 100 ml of benzene, cooled, and cooled to 100 ml of distilled water at 10 ° C. or lower, 10.5 g of p-toluene sulfonyl chloride, and tri 0.46 g of ethyl benzyl ammonium chloride was added sequentially, followed by dropwise addition of 16 ml of sodium hydroxide 5N aqueous solution for 1 hour. After stirring for 1 hour at 10 DEG C or lower, 10.5 g of p-toluene sulfonyl chloride was further added, and 16 ml of an aqueous sodium hydroxide 5N solution was added dropwise for 1 hour. The reaction mixture was stirred vigorously at 5 ° -10 ° C. for 3 hours and the benzene layer was separated. After washing twice with 30 ml of a 20% aqueous solution of sodium chloride, dried over potassium carbonate, filtered with activated carbon at room temperature, and the filtrate was concentrated under reduced pressure. The residue is dissolved in 60 ml of acetone and left for 3 hours at 5 ° C. or lower to remove a small amount of insoluble material by filtration. The solvent was concentrated under reduced pressure again to obtain 33.2 g of the title compound.

TLC: (silica gel / chloroform: 2-propanol: 25% aqueous ammonia = 10: 10: 1), Rf = 0.92

Elemental analysis: C ₁₇ H ₂₃ NO ₄ S ₂ (369.49)

Theoretic value (%): C 55.26, H 6.27, N 17.35

Found (%): C 55.23, H 6.35, N 17.30

Example 9

1-amino-1-methylamino-2-nitroethene

After dissolving 44.4 g of 1-methylamino-1-methylthio-2-nitroethene in 220 ml of 95% ethanol, 250 ml of 28% aqueous ammonia was added dropwise at room temperature for 2 hours. The reaction solution is stirred at 25 ° -35 ° C. for 12 hours and then depressurized to remove the gas. The yellow solid obtained by concentrating the solvent under reduced pressure was put in 150 ml of acetone, stirred vigorously at room temperature for 2 hours, filtered, and washed twice with 30 ml of acetone. The resulting pale yellow crystals were dried at 50 ° C. or lower to obtain 30.8 g of the title compound.

Melting Point: 186 °-187 ℃

Elemental Analysis: C ₃ H ₇ N ₃ O ₂ (117.11)

Theoretic value (%): C 30.77, H 6.02, N 35.88

Found (%): C 30.70, H 6.08, N 35.94

TLC: (silica gel / chloroform: 2-propanol: 25% aqueous ammonia = 10: 10: 1), Rf = 0.19

IR (KBr): 3350, 3250, 3200, 1610, 1425, 1225, 955, 770, 720, 665 cm ^-1

Example 10

Hydrochloride (1: 1) of N- [2-[[[5- (dimethylamino) methyl-2-furanyl] methyl] thio] ethyl] -N'-methyl-2-nitro-1,1-ethenediamine

32.5 g of 2-[[[5- (dimethylamino) methyl-2-furanyl] methyl] thio] ethyl iodine was dissolved in 160 ml of chloroform, and then 12.88 g of 1-amino-1-methylamino-2-nitroethene was dissolved. Add 80 ml of water, 15 ml of sodium hydroxide 10N solution, and 0.34 g of tetra n-butyl ammonium sulfite. The reaction mixture was slowly heated to react at 40 ° -50 ° C. for 10 hours, cooled to separate the organic layer, and the water layer was extracted two more times with 30 ml of chloroform. The combined organic layers are washed with 50 ml of 10% aqueous sodium hydrogen carbonate solution and twice with 30 ml of 20% aqueous sodium chloride solution. The oily residue obtained by concentrating the solvent under reduced pressure was dissolved in 65 ml of 2-propanol, treated with activated charcoal at room temperature, and the filtrate was concentrated under reduced pressure again. This liquid, obtained in free base form, is again dissolved in 180 ml of 2-propanol and slowly added 8.7 ml of 35% hydrochloric acid. After stirring for 12 hours, the mixture was cooled, filtered at 15 ° C., washed with 40 ml of 2-propanol and 50 ml of acetone, and dried under reduced pressure at 50 ° C. or lower to obtain 32.6 g of the titled compound.

Melting Point: 139- 141 ℃

Elemental analysis: C ₁₃ H ₂₂ N ₄ O ₃ S.HCl (350.87)

Theoretic value (%): C 44.50, H 6.61, N 15.97

Found (%): C 44.48, H 6.65, N 15.95

Example 11

Hydrochloride (1: 1) of N- [2-[[[5- (dimethylamino) methyl-2-furanyl] methyl] thio] ethyl] -N'-methyl-2-nitro-1,1-ethene diamine

To 80 ml of toluene, 11.7 g of 1-amino-1-methylamino-2-nitroethone, 8.3 g of anhydrous potassium carbonate, 4.4 g of powdered sodium hydroxide, and 0.34 g of tetra n-butyl ammonium sulfite were added sequentially, at room temperature under a nitrogen atmosphere. Stir for 2 hours.

28.35 g of hydrochloride (1: 1) of 2-[[[5- (dimethylamino) methyl-2-furanyl] methyl] thio] ethyl chloride was dissolved in 140 ml of water, and then 11 ml of an aqueous 10N aqueous sodium hydroxide solution was added at 15 ° C. or lower. It is added and extracted four times with 50 ml of toluene. Washed with 40 ml of 20% aqueous sodium chloride solution, and dried over sodium sulfate to obtain a toluene solution of the chloro compound. This solution is added dropwise to the toluene mixture solution prepared for 1 hour. The reaction mixture is slowly heated to reflux for 10 hours, cooled to room temperature, and the inorganic salts are filtered off. 150 ml of dichloromethane is added to the filtrate, and 200 ml of 0.5 N hydrochloric acid is slowly added thereto at 20 ° C. or lower, followed by vigorous stirring for 30 minutes, and then the water layer is separated. The aqueous layer was washed twice with 50 ml of chloroform and then slowly added with 5 N aqueous sodium hydroxide solution to adjust the pH to 10.2-10.5. The mixture was stirred for 30 minutes, extracted four times with 80 ml of dichloromethane, and the organic layer was washed with 50 ml of 10% aqueous sodium hydrogen carbonate solution. The residue in the oily phase obtained by concentrating the solvent under reduced pressure was determined by treatment in the same manner as in Example 10 to obtain 31.2 g of the same title compound.

Melting Point: 140 °-141 ℃

Example 12

Hydrochloride (1: 1) of N- [2-[[[5- (dimethylamino) methyl-2-furanyl] methyl] thio] ethyl] -N'-methyl-2-nitro-1,1-ethenediamine

Reaction was carried out in the same manner as in Example 10, using 2-[[[5- (dimethylamino) methyl-2-furanyl] methyl] thio] ethyl bromide as a starting material and triethylbenzyl ammonium bromide as a phase transfer catalyst. And the same to give the same title compound in 92% yield.

Melting Point: 139 ° ~ 141 ℃

Example 13

Hydrochloride (1: 1) of N- [2-[[[5- (dimethylamino) methyl-2-furanyl] methyl] thio] ethyl] -N'-methyl-2-nitro-1,1-ethene diamine

36.9 g of 2-[[[5- (dimethylamino) methyl-2-furanyl] methyl] thio] ethyl p-toluene sulfonate obtained in Example 8 was dissolved in 150 ml of distilled water and 30 ml of N, N-dimethylformamide. After 22 ml of sodium hydroxide 5N aqueous solution was added at 占 폚 or lower, 14.05 g of 1-amino-1-methylamino-2-nitroethene was dissolved in 80 ml of distilled water and added dropwise for 2 hours. Stir at room temperature for 20 hours, then heat to 55 ° -60 ° C. for 1 hour. After cooling again, 20 ml of an aqueous sodium hydroxide 1N solution was further added at 15 ° C. or lower, and extracted four times with 80 ml of chloroform. The combined organic layers were treated after the reaction as in Example 10 to obtain 31.6 g of the same title compound.

Melting Point: 139 °-141 ° C

Elemental analysis: C ₁₃ H ₂₂ N ₄ O ₃ S.HCl (350.87)

Theoretic value (%): C 44.50, H 6.61, N 15.97

Found (%): C 44.53, H 6.67, N 15.89

TLC: (product of Examples 10-13)

(a) (silica gel / ethyl acetate: methanol: 25% aqueous ammonia = 1: 5: 1), Rf = 0.73

(b) (silica gel / ethyl acetate: 2-propanol: 25% ammonia number = 4: 3: 1), Rf = 0.37

(c) (silica gel / chloroform: 2-propanol: diethylamine = 4: 3: 2), Rf = 0.43

(d) (silica gel / toluene: methanol: diethylamine = 9: 1: 1), Rf = 0.11

Claims (2)

A compound of formula (VII) is reacted with a halogenating reagent or p-toluene sulfonyl chloride to prepare a compound of formula (XI) having a leaving group introduced therein, followed by reaction with a nitroethene derivative of formula (XIII) A novel process for preparing amino alkylfuran derivatives of salts thereof and salts thereof.

The process according to claim 1, wherein the reaction is carried out using a phase transfer catalyst such as tetraalkylammonium sulfite, tetraalkyl ammonium halogen salt, trialkylbenzyl ammonium halogen salt, or the like.