Method of obtaining pyrimidine derivatives or salts thereof

专利摘要:
2-Amino-4-substituted-5-(hydroxy or alkoxy)-pyrimidines, which may be 6-substituted, and derivatives thereof are inhibitors of leukotriene synthesis and are therefore useful for the treatment of pulmonary, inflammatory, allergic and cardiovascular diseases. The compounds are also cytoprotective and therefore useful in the treatment of peptic ulcers.
公开号:SU1574171A3
申请号:SU864027808
申请日:1986-07-23
公开日:1990-06-23
发明作者:Ламаттина Лоренс；Джадсон Волкер Фредерик
申请人:Пфайзер Инк (Фирма)；
IPC主号:

专利说明:

This invention relates to a process for the preparation of new pyrimidine derivatives having valuable pharmacological properties, and can be used in medicine.
The purpose of the invention is to obtain new pyrimidine derivatives with a higher inhibitory activity of leukotriene synthesis.
Example 1. 2- (p-Chlorophenyl-propylamino) -4,6 dimethyl-5-hydroxypyrimidine.
5-Acetoxy-4,6-dimethyl-2- (p-chlorophenylpropylamido) pyrimidine (0.27 g, 0.78 mol) is treated with 3.5 ml
(3.5 mmol) of 1 M solution of diisobutylaluminium hydride in hexane at -23 ° C in anhydrous tetrahydrofuran (5 ml) under nitrogen atmosphere for 3 hours. The reaction mixture was quenched with 15 ml of an aqueous solution of ammonium chloride and stirred at room temperature overnight. The reaction mixture is then filtered and the filtrate is extracted with 40 ml of ethyl acetate. The extracts are dried, concentrated and chromatographed using a mixture of hexane and ethyl acetate (1: 1) as an eluent, to give 0.1 g (37%) of the crystalline compound, t. square 124-126 ° C.
Oi 1
J

04
Example 2. 2- (n-Methylphenyl-Propylamino) -4,6-dimethyl-5-hydroxypyrimidine.
5-Acetoxy-4,6-dimethyl-2- (p-methylphenylpropylamido) pyrimidine (7.7 g, 24 mmol) is treated with 1 M solution of diisobutylaluminum hydride in hexane (94 ml, 94 mmol) in an anhydrous solution of tetrahydrofuran (150 ml ) at -35 ° C in a nitrogen atmosphere. After 3.5 h, the reaction mixture was quenched with saturated (aqueous ammonium chloride solution (100 ml), brought to room temperature and stirred for an hour. After filtration, a clear solution was obtained, which was diluted with 100 ml of water and extracted with 250 ml of ethyl acetate The anhydrous extracts are concentrated and chromatographed on silica gel (1: 1, hexane and ethyl acetate) to give 2.0 g (31%) of the title compound, mp 103-104 ° C.
EXAMPLE 3 Analogously to Example 1, the following compounds were prepared:
2 (p-nonylamino) 4,6-dimethyl-5-hydroxypyrimidine,
NMR (CDCl1): 0.8-1.6 (m, 17H); 2.25 (s, 6H); 3.1-3.4 (m, 2H);
4,6-dimethyl-5-hydroxy-2-phenylhexacyl-symlynopyrimidine, m.p., 43-45 C;
4-isopropyl-5-hydroxy-6-methyl-2-p-chlorofenshropylaminopyrimidine,
NMR (CDC13): 7.10 (m, 4H); 4.20 (broad s., Ø); 3.30 (m., ЗН); 2.6 (m, 2H); 2.3 (s., NN); 1.80 (m, 2H) 1.2 (d, 6H);
4-isopropyl-5-hydroxy-6-methyl-2-nonylaminopyrimidine,
NMR (CDC15): 6.30 (bs, Sh); 4.75 (broad s., Ш); 3.55-3.10 (m. ZY); 2.30 (s., NN); 1.60-0.90 (m, 23H).
PRI me R 4. A mixture of 3-acetoxy-5-methyl-2,4-hexanedione (5 g, 27 mmol and quinidine acetate (6.4 g, 54 mmol) in 100 ml of dimethylformamide is heated at 100 ° C in for 3 h. The mixture is cooled, concentrated and filtered through silica gel using a mixture of equal parts by volume of hexane to ethyl acetate as eluent. The filtrate is concentrated and the residue is treated with excess acetic anhydride in the presence of triethylamine. The reaction mixture is concentrated and the residue is subjected to crystallization from coil hexane get 1.7 g

Q
0
(31%) 5-acetoxy-2-amino-4-isopropyl-6-met-shshirimidine, m.p. 141-142 C.
A solution of the obtained compound (0.5 g, 2.4 mmol) in pyridine is treated with 6-phenylhexanoic acid chloride (3.6 mmol) at 0 ° C for 0.5 h. The reaction mixture is heated to 25 ° C and maintained at this temperature for 0.5 h. The reaction mixture is concentrated and the residue is chromatographed on silica gel using a mixture of hexane and ethyl acetate (3: 1) as an eluent to give 0.66 g (72%) of 5-acetoxy-4-isopropyl alcohol. drank-6-methyl-2-phenylhexylamidopyrimidine.
NMR (CBC1E): 8.28 (bs, Sh); 7.20 (s, 5H); 3.20-2.50 (m, 5H); 2.35 (s ,, a); 2.25 (s., NN); 1.90-1.40 (m, 6H); 1.08 (d, 6H).
The resulting compound was reacted according to the method of Example 3 and 4-isopropyl-5-hydroxy-6-methyl-2-phenylhexylaminopyrimidine was obtained, m.p. 60-61 ° C.
EXAMPLE 5. 2-Dimethylamino-4-isopropyl-6-methyl-5-hydroxypyrimidine.
A. 3-Acetoxy-5-methyl-2,4-hexadione (3 g, 16 mmol), 1,1-dimethyl-quinidine sulfate (4.4 g, 16 mmol) and sodium acetate (2.6 g, 32 mmol) are added to dimethylformamide and heated under nitrogen at 100 ° C for 4 hours. The reaction mixture is cooled and concentrated. The mixture is chromatographed on silica gel (9: 1, hexane: ethyl acetate) to obtain 0.4 g of 5-acetoxy-2-dimethylamino-4-isopropyl-6-methyl-pyrimidine as a brown oil.
NMR (SBS1E): 3.2 (s, 6H); 3.0-2.5 (s., ZN); 2.1 (s ,, a); 1.1 (d., Bn).
The resulting compound (0.3 g, 1.3 mmol) was dissolved in anhydrous tetrahydrofuran, cooled to -35 ° C under nitrogen and treated with a 1 M solution of diisobutyl aluminum hydride (2.6 ml, 2.6 mmol) in hexane. After 1 h, the reaction temperature was raised to 0 ° C for 1 h and quenched with 10 ml of an aqueous solution of ammonium chloride. The mixture was filtered, extracted with 25 ml of ethyl acetate, dried with magnesium sulfate, and concentrated to give 0.24 g of the title compound, m.p. 82-83 ° Co
PRI and, meer 6. According to the method of example 5B receive 2-dimethylamino-4-methyl5 1
6-phenyl-5-hydroxypyrimidine, m.p. 125.5-127.5 ° C, from 2-dimethylamino-4-methyl-6-phenyl-5-acetoxypyrimidine, obtained by the method of Example 5A.
NMR (CDC13): 8.3-7.3 (m, 5H); 3.3 (s, 6H); 2.3 (s., NN); 2.1 (s., ZN).
Example 7. Analogously to Example 4B, the following intermediates are obtained:
5-acetoxy-2-p-chlorophenylpropyl-amino-4-isopropyl-6-methylpyrimidine,
NMR (CDC13): 7.20 (s, 4H); 3.3-2, (m., 5H); 2.35 (s., NN); 2.30 (s., NN); 1.21 (d, 6H);
5-acetoxy-2-nonyl-4-isopropyl-6-methylpyrimidine,
NMR (CDCl1): 3.5-2.8 (m, 3N); , 2.35 (s., ZN); 2.30 (s., NN); 1.5-0.8 (m, 21H).
II p and mep 8. 4,6-Dimethyl-5-methyroxy-2-phenylpentylaminopyrimidine.
4; 6-Dimethyl-5-hydroxy-2-phenylpentylaminopyrimidine (0.5 g, 1.8 mmol) prepared as described in Example 1, dissolved in anhydrous tetrahydrofuran (20 ml) under nitrogen atmosphere and treated with sodium hydride (0, 07 g
1.8 mmol, 60% dispersion in oil. The reaction mixture is stirred at
O C for 2 hours. Dimethyl sulfate (0.11 ml, 1.8 mmol) is added with a syringe and the reaction mixture is stirred for another 1 hour. The reaction is then quenched with a saturated aqueous solution of ammonium chloride (20 ml), the reaction mixture extracted with ethyl acetate (75 ml). The extracts are washed with 50 ml of water and 50 ml of saturated sodium chloride solution, dried with magnesium sulfate and concentrated. After chromatography on silica gel, 0.15 g of the title compound is used as a yellow oil, m.p. 31-33 ° C.
NMR (CDC13): 7.2 (s, 5H); 3.6 (s., NN); 3.4 (m, 2H); 2.6 (m., 2H)
2.3 (s. 6H); 1.6-1.4 (m., 6H). Example9. By way of example
8, 4,6-dimethyl-5-methoxy-2-phenylhexylaminopyrimidine is obtained.
NMR (CDC13): 7.14 (bs, 5H);
4.9 (bs, 1H); 3.63 (s., ZN);
3.4 (m, 2H); 2.6 (m, 2H); 2.3 (s, 6H); 1.3-1.4 (m., 8H).
Example 10. 5-Methoxy 4-methyl 2-phenylhexylaminopyrimidine-phenylhexyl.
0
five
0
0 5
0
five
five
716.
Sodium hydride (60% starting dispersion in oil, 58 mg, 1.45 mmol) is washed twice with pentane in a dry flask filled with nitrogen. The residue was diluted with 4 ml of anhydrous tetrahydrofuran, and 320 g (1 mmol) of 5-methoxy 4-methyl-2 feshexyl-pyrimidium was added in portions at 0 ° C. After the reaction mixture was stirred for half an hour, dimethyl sulfate was added to it. The reaction mixture is cooled to room temperature for 1 hour, then diluted with 10 ml of saturated ammonium chloride and extracted four times with 25 ml of ethyl acetate. The extracts are combined, dried with magnesium sulfate and concentrated, to obtain 374 mg of oil. After chromatography on silica gel using a mixture of ethyl acetate and hexane (1: 1) as eluent, 130 mg of an oil is obtained, which crystallizes upon storage, the crystals of this product have a m.p. 39-40 C.
Example 11. Analogously to example 10, get 4- (3,4-dichlorophenyl) -2-dimethylamino-5-methoxypyrimidine, 1.pl. 72-73 ° C;
4- (3,4-dichlorophenyl) -2-dpmllamino-5-ethoxypyrimidine, m.p. 69-70 ° C;
2- (p-chlorophenylpropylamino) -4,6-dimethyl-5-methoxypyrimidine, m.p. 84-85: p.
Example 12. 2-Phepilhexylamino-4-methyl-5-hydroxypyrimidine sodium salt.
Sodium hydride (50% dispersion oil, 337 mg) is washed with hexane to remove the oil, dried in vacuo and mixed with tetrahydrofuran. The resulting mixture was cooled with an ice bath and treated with a solution of 2- (n hexylphenyl) 4-methyl-5-hydroxypyrimidine (2 g) in tetrahydrofuran. The cooled mixture was stirred at 0 ° C for 30 minutes, concentrated to a greenish foam. Ethyl alcohol is added to the mixture and the mixture is concentrated. Toluene is then added and the mixture is concentrated in vacuo to a solid. Yield 2.01 g, m.p. 128-131 ° C.
Example 13. 2-Phenylpentylamino-4,5-dimethyl-5-methoxypyrimidich | phosphate.
IS09 g of 2-phenylpentylamino-4,6-dimethyl-5-methoxypyrimidine is dissolved in 15 ml of isopropyl alcohol and cooled to 0 ° 0. Phosphoric acid (85%, 9 g) is then added and the mixture is stirred at 0 ° C for 30 minutes. After removal of the isopropyl alcohol, a white precipitate is obtained, washed with pentane and dried under vacuum at 45 ° C, mp. 107-108 ° C.
Example 14. In analogy to Example 13, compounds of the formula
CH3
CLT-ORC
A hw nzro
V N N Rl
1H
are given in table. one.
The LO / CO inhibitory activity in the cell system for the compounds obtained by the proposed method is determined as follows.
RBci I cells maintained in a monolayer are grown for 1 or
2 days by stirring the culture using the minimum essential medium containing the salt of Earl giyus 15% calf serum with the addition of an antibiotic (antifungal) solution.
The cells were washed once with RPFI 1640 and then resuspended on EPMI 1640 incubation medium with a cell density of 1,107 cells / ml. Separate portions of cell suspension with a volume of 0.5 ml are preincubated at a temperature of about 30 ° C for 10 minutes with 1 μl of the drug solution in DMSO. Incubation begins with the simultaneous addition of 5 µl (14C) - arachidonic acid in ethanol and 2 µl of the preparation A-23187 in DMSO with,, in order to obtain final concentrations of 5 and 7.6 µmol, respectively. by adding 0.27 ml of a mixture of acetonitrile / acetic acid (100; 3 by volume). The mixture is clarified by precipitation of the proteins by centrifugation.
To carry out high pressure liquid chromatography, a volume of 200 µl of the clarified sample is sprayed onto a Radar Cn CN column (inner diameter 55 mm), which is eluted using acetonitrile / Eodo / acetic acid mobile phase with acetonitrile acid.
five
0
five
0
five
0
five
five
tonitrile from 35 to 57% for 10 minutes with a volumetric flow rate of 1 ml / min. Radioactivity detection and on-line integration of the peak areas is carried out using a Bertold-504 radioactivity monitor equipped with a built-in integrator and a 800 µl cell mixing 2.4 ml / min of omnifluor (New England Nyklea) with a stream, arising from the column. The area under the curve (AUC), measured with an integrator for each product, is compared with the average AUC value for control (untreated) samples. The results, converted to a percentage of the control, are related to the logarithm of the concentration of the drug. The four-point dose response curves are constructed from two experiments. The dose increase is 4x. The half maximum inhibition point (ICD.0-value) is estimated using graphical interpolation.
Results obtained for compounds of general formula
s
 .
HRiN-V4
Tables 2 and 3 are given (in each case, the standard deviation does not exceed ± 15%), moreover, HZ is CH3 (for Table 2) and Ke is H (for Table 3).

权利要求:
Claims (1)
[1]
Invention Formula
The method of obtaining derivatives. Pyrimidine general formula
H3
TSKVOR / t
. RiNH-V
where R, ™ St-C4Ј-phenylalkyl 5 substituted in phenyl by chlorine, fluorine or C1-Ce alkyl; C C-alkyl;
1C hydrogen or C-Cg-alkyl, or their salts, equivalent to a compound of the general formula
R3 O N r-OAcyl
R5CNH V 4
where Rji-R has the indicated meanings; R5 is suitably substituted with C 6 -C ,, -phenyl-alkyl, is subjected to reduction with alkyl aluminum hydride in an inert solvent, followed by isolation of the desired
the product in the form of a base or a salt, or, if necessary, the obtained compound (1), where R is hydrogen, is alkylated with a compound, where X is an alkylsulfonyl group, to produce compound (1), where R4 is alkyl.
Table I
Phosphate salt.
eleven
157417112
T a 6 l and (c a 3
ek-
ek
silt
I R I 1C | m.p., ° s |
p-C1-phenyl N m-CPe-f-N
NILE
o-F-phenyl N p-C1-phenyl N
Phenyl
Ch3
Phenyl
n to
H
sna
H
H N
84-85 48-50
Oil 0 154-155 0
Oil 39-40 Oil
n n
Editor N. Bobkova
Compiled by S.Pov Kova Tehred M.Hodanich
Order 1649
Circulation 324
VNIIPI State Committee for Inventions and Discoveries at the State Committee on Science and Technology of the USSR 113035, Moscow, Zh-35, Raushsk nab 4/5
Production and publishing plant Patent, Uzhgorod, st. Gagarin, 101
m.p. ° |
84-85 48-50
BO / CO
0.22 / 1.6 0.99 / 33
Oil 0.23 / 9.6 154-155 0.87 / 50
uh
Oil 39-40 Oil
n n
0.1 / 11 0.7 / 17 0.4 / 7.3
0.5 / 7.4 0.55 / 15
Proofreader L. Patay
Subscription

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引用文献:

---

公开号 | 申请日 | 公开日 | 申请人 | 专利标题

---

---

IN153791B|1979-03-10|1984-08-18|Soc D Etudes Prod Chimique|

---

US4659363A|1983-07-25|1987-04-21|Ciba-Geigy Corporation|N--2-aminopyrimidine derivatives, the preparation and use thereof|

---

US4554276A|1983-10-03|1985-11-19|Pfizer Inc.|2-Amino-5-hydroxy-4-methylpyrimidine derivatives|

---

EP0164204A1|1984-05-12|1985-12-11|FISONS plc|Novel pharmaceutically useful pyrimidines|SG47583A1|1986-01-13|1998-04-17|American Cyanamid Co|4,5,6-Substituted-n--2- pyrimidinamines|

---

US4959365A|1986-10-31|1990-09-25|Pfizer Inc.|Topical compositions of lipophilic pharmaceuticals agents|

---

HU199683B|1987-07-22|1990-03-28|Egyt Gyogyszervegyeszeti Gyar|Process for producing pharmaceutical compositions analgesic, antiphlogistic, antipyretic, antianginic and/or antioxidative activity|

---

WO1989005295A1|1987-12-02|1989-06-15|Pfizer Inc.|Acyl derivatives of hydroxypyrimidines|

---

DE68910288T2|1988-12-14|1994-02-17|Pfizer|Derivatives of 5-hydroxy and 5-methoxy-2-aminopyrimidine as inhibitors of interleukin-1 production.|

---

US5071852A|1988-12-14|1991-12-10|Pfizer Inc.|Derivatives of 5-hydroxy and 5-methoxy 2-amino-pyrimidines as inhibitors of interleukin-1 production|

---

US4940712A|1989-05-26|1990-07-10|Pfizer Inc.|Derivatives of hydroxyprimidines as leukotriene synthesis inhibitors|

---

US5248682A|1991-01-31|1993-09-28|Warner-Lambert Company|2-substituted-4,6-di-tertiary-butyl-5-hydroxy-1,3-pyrimidines useful as antiinflammatory agents|

---

EP0569493A4|1991-01-31|1993-11-24|Warner-Lambert Company|Substituted 4,6-di-tertiary-butyl-5-hydroxy-pyrimidines|

---

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法律状态:

优先权:

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申请号 | 申请日 | 专利标题

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US06/758,199|US4711888A|1985-07-24|1985-07-24|Hydroxy and alkoxy pyrimidines|

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