TW472057B - Pyrrolopyrimidines and processes for the preparation thereof - Google Patents

Abstract

Described are 7H-pyrrolo[2,3-d]pyrimidine derivatives of formula I, wherein the symbols are as defined in claim 1. Those compounds inhibit tyrosine protein kinase and can be used in the treatment of hyperproliferative diseases, for example tumour diseases.

Description

472057 Α7 Β7 V. Description of the invention () The present invention relates to 7H-larrolo [2,3-d] pyrimidine derivatives, the preparation method and the novel intermediates used for the preparation, the pharmaceutical composition containing the derivatives, and these derivatives Use of medicine as medicine. The present invention relates to a 7H-pyrrolidine [2,3-d] -pyridine derivative and a salt thereof of formula (I),

Printed by the Central Standards Bureau of the Ministry of Economic Affairs, Consumer Cooperatives, q is 0 or η is 1 to 3 (when q is 0), or η is 0 to 3 (when q is 1), R is halogen, lower alkyl, hydroxyl , Lower alkoxy, lower alkoxy, carboxyl, lower alkoxycarbonyl, carbamoyl, N · lower alkane-carbamoyl, N, N-di-lower home-carbamoyl, cyano, Amino, lower alkylamino, lower alkylamino, N, N-di-lower alkylamino or trifluoromethyl, when there are several radicals R in the molecule, these radicals may be the same or different, 3 ) & and 112 are each independently: 〇0 is carbamic acid-methoxy, carboxy-methoxy, benzyloxy methoxy, lower alkoxy curtain-methoxy, phenyl, amine, lower Alkylamino, lower alkylamino, N, N-di-lower alkylamino, hydroxyl, lower alkyloxy, carboxyl, lower alkoxycarbonyl, carbamoyl, N-lower alkylaminocarbamyl, N, N-di-lower alkyl-carbamoyl, cyano or nitro substituted phenyl; β) hydrogen; γ) pyridyl which is unsubstituted or substituted with halo or lower alkyl; -----— (Please read the note on the back first Please fill in this page again) The size of the paper is applicable to China National Standard (CNS) A4 specification (210X297mm) 472057 A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of invention () -B than indan-2-yl, naphthyl, cyano, carboxyl, lower alkoxycarbonyl, carbamoyl, N-lower alkyl-carbamoyl, Ν, Ν-di-lower alkyl-carbamoyl, N-Methyl-Aminomethylamido, methylamido, lower alkylfluorenyl, lower alkenyl, lower alkenyloxy; or ε) lower alkyl substituted with the following substituents: εο〇 halogen, amine, lower alkylamine , Hexahydropyridyl, di-lower alkylamino, εβ) unsubstituted aniline or halides, lower alkyl, hydroxyl, lower alkoxy, lower alkoxy, carboxyl , Lower alkoxycarbonyl, carbamoyl, N-lower alkyl-carbamoyl, N, N-di-lower alkyl-carbamoyl, cyano, amine, lower alkylamino, lower alkylamino , N, N-di-lower alkylamino or trifluoromethyl substituted aniline, εγ) hydroxyl, lower alkoxy, cyano, carboxyl, lower alkoxycarbonyl, amine Amidino, N-lower alkyl-carbamoyl, N, N-di-lower alkyl-carbamoyl, mercapto, or εδ) are free radicals of formula RrSPk- (where R3 is lower alkyl and m is 0, 1 or 2) a substituted aniline group, or b) when q is 0, one of the radicals 112 and 112 is an unsubstituted lower alkyl group or an unsubstituted phenyl group, and the radicals and & The other has the meaning specified in a) above (apart from hydrogen), or (〇 & together with ^ is an amino group, a lower alkylamino group, a lower alkylamino group, N, N-di-lower alkyl group Amine, Nitro, Halogen, Hydroxyl, Lower Alkyloxy, Carboxyl, Lower Alkoxycarbonyl, Carbamate, N-Lower School-Carbamate, N, N-Di ------ --I-(Please read the notes on the back before filling this page) The paper size of this edition applies to the Chinese National Standard (CNS) A4 specification (2) 0 × 297 mm) 472057 Α7 Β7 Central Bureau of Standards, Ministry of Economic Affairs Printed by employee consumer cooperatives V. Description of the invention () Lower grades-Carbamate or cyano-substituted CrCurl, 4-alkylene dienyl, or η-1,4- with up to 9 carbon atoms Butanedienyl, or d) q When it is 1, & and d are independent, are unsubstituted lower alkyl or unsubstituted phenyl, or have one of the meanings specified in a) above, and Re is hydrogen, lower alkyl, or lower alkyl Oxycarbonyl, carbamoyl, N-lower fluorenyl-carbamyl or N, N-di-lower fluorenyl-carbamyl, and η in formula (I) is 0, q is 1, & and Except compounds which are each hydrogen and & methyl. The prefixes and lower 〃 used above and below represent radicals of up to 7 (inclusive), especially up to 4 (inclusive), especially 1 or 2 carbon atoms. η is preferably 2 or especially 1. When there is only one substituent R, the substituent is preferably at the 3-position of the phenyl ring. When two substituents R are present, those substituents are preferably 3 and above. Halogen R is bromine, iodine or more suitably fluorine or chlorine. When η is 1, R is preferably chlorine. Lower alkyl is, for example, methyl. The lower alkoxy group is, for example, ethoxy group. Lower alkoxy is, for example, methoxy. Lower alkoxycarbonyl is, for example, methoxycarbonyl. The NH-lower-class carbamoyl group is, for example, n-methylaminocarbamyl, Ν- (ΙΕ 丁) -carbamoyl, or Ν- (3-methyl-butyl-l-yl) -carbamoyl醯 基. N, N-di-lower-class carbamoyl is, for example, N, N-dimethyl-carbamyl. Lower alkylamino is, for example, acetamido. --------- II (Please read the notes on the back before filling in this page) l · The paper size of the lamp is applicable to the Chinese National Standard (CNS) A4 specification (2 丨 0X297 mm) -6-472057 A7 B7 Printed by the Central Standard of the Ministry of Economic Affairs, Coconut Consumer Cooperative, V. Description of the invention () The lower alkylamine group is, for example, methylamine group. N, N-di-lower alkylamino is, for example, dimethylamino. Lower alkoxy-methoxy is, for example, methoxycarbonyl-methoxy. The substituted phenylgen or & may carry one or more, but preferably no more than three substituents (which may be the same or different). The substituted phenylene or R2 preferably bears only one substituent, which may be in the ortho, meta or more preferably para position. The phenyl substituted by phenyl & or 112 is, for example, biphenyl, and more preferably 4-biphenyl. Pyridyl is, for example, 2-pyridyl. The free radical & or halogen in the radical is fluorine, bromine, iodine or more suitably chlorine. Naphthyl is, for example, 2-tidyl. Lower alkenyl is, for example, ethenyl, propionyl or prop-2-canyl (diluted propyl). Lower alkenyloxy is, for example, vinyloxy, prop-1-yloxy or prop_2_yloxy (allyloxy). The substituted lower alkyl & or 112 may carry one or more, but preferably not more than three substituents (which may be the same or different). Substituted lower alkyl groups or groups preferably carry only one substituent. Lower alkyl & substituted with aniline (anil is unsubstituted or halogen, lower alkyl, hydroxyl, lower alkyloxy, lower alkyl, oxo, lower Homoxyl, carbamate, lower alkane-amine formamidine, N, N-di-lower academy-amine formamidine, cyano, amine, low (Please read the precautions on the back before filling this page ) This paper size applies to China National Standard (CNS) Λ4 specification (210X297 mm) 472057 Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs A7 B7 5. Description of the invention () Grade alkylamine, lower alkylamine, N (N-di-lower alkylamino or trifluoromethyl substituted) is particularly a methyl substituted in this manner, such as aniline-methyl or 4-methoxy-aniline-methyl.

CrC1 < rl, 4-dienadienyl is divalent but-1,3-diene, in which each terminal carbon atom 1 and 4 has a free valence, and it can be substituted by a lower alkyl group, however, the radicals in total There are no more than 10 倜 carbon atoms, such as the butane-1,3-dioxo-M- group. Ϊ́γ-1,4 · alkanedienyl group with up to 9 carbon atoms is defined as above. C1 (rl, 4-alkanedienyl group, at least one of which is preferably a butadiene chain Whose carbon atom (especially like the terminal carbon atom of the butadiene chain) has been replaced by nitrogen, such as 1-fluorene-1,4-alkylene dienyl, especially like 1-nγ-butylene_1 , 3-diene-1,4-yl. Acryl-1,4-alkanedienyl preferably contains 1 to 3 nitrogen atoms, especially only 1 nitrogen atom. There is only one nitrogen atom. The ι, 4 · alkanedienyl group is preferably bonded to the 6th carbon atom of the 7Η-pyrrolo [2,3-d] pyrimidine ring system via the nitrogen atom. The salt of the compound of the formula (I) is particularly organic Or acid addition salts produced by inorganic acids, especially non-toxic salts that are pharmaceutically acceptable. Suitable inorganic acids are, for example, carbonic acid (preferably in the form of carbonate or bicarbonate), hydrohalic acid (like hydrochloric acid), Sulfuric acid or phosphoric acid. Suitable organic acids are, for example, carboxylic acids, phosphonic acids, sulfonic acids or aminesulfonic acids, such as acetic acid, propionic acid, caprylic acid, capric acid, dodecanoic acid, glycolic acid, lactic acid, 2-butyric acid , Grape acid, glucose alone Acid, fumaric acid, succinic acid, adipic acid, pimelic acid, succinic acid, azelaic acid, malic acid, tartaric acid, citric acid, gluconic acid, galactic acid, amino acids (like glutamine Acid, aspartic acid, N-methylglycine, acetoacetic acid, N-acetic acid aspartic acid or N-acetic acid), pyruvate, acetoacetic acid, phosphorus China National Standard (CNS) Λ4 specification (2 丨 〇〆297mm) (Please read the precautions on the back before filling out this page) " δ Γ -8- 472057 5. Description of the invention () Acid serine, 2- or 3-glyceryl phosphate, glucose-6-phosphate, gluconic acid-1-phosphate, fructose-1,6-diphosphate, maleic acid, hydroxymaleic acid, maleic acid, Cyclohexyl formic acid, adamantane carboxylic acid, benzoic acid, salicylic acid, 1- or 3-hydroxynaphthalene-2-junic acid, 3,4,5-trimethoxybenzoic acid, 2-phenoxybenzoic acid, 2-acetamidine Oxybenzoic acid, amine salicylic acid, phthalic acid, phenylacetic acid, phenylglycolic acid, cinnamic acid, nicotinic acid, isonicotinic acid, glutamic acid, galacturonic acid, methanesulfonic acid or ethanesulfonic acid, 2- Via ethanesulfonic acid, ethane-1,2-disulfonic acid Benzenesulfonic acid, 2-chalconic acid, 1,5-naphthalene-disulfonic acid, 2-, 3-, or 4-methylbenzenesulfonic acid, methylsulfuric acid, ethylacetic acid, dodecylsulfonic acid, N-cyclohexylaminesulfonic acid Acid, N-methyl-, N-ethyl-, or N-propyl-amine sulfonic acid; or other organic protonic acid, such as ascorbic acid ^ Compounds of formula 有 with at least one free carboxyl group can form internal or metal salts or ammonium salts, Like alkali metal or alkaline earth metal salts, such as sodium, potassium, magnesium or calcium salts, or with ammonia or a suitable organic amine (like a third monoamine, such as triethylamine or tris (2-hydroxyethyl) amine ) Or heterocyclic bases (such as N-ethyl-hexahydropyridine or N, N'-dimethyl-hexahydropyridine traps). Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (please read the note on the back first) For the purpose of isolation or purification, salts that are not pharmaceutically acceptable, such as picrates or perchlorates, can also be used. Only pharmaceutically acceptable salts and non-toxic salts (at appropriate dosages) are used medically, so those salts are preferred. Given the close relationship between free-form novel compounds and their salt forms, including those that can be used, for example, for the purification or identification of novel compounds, as intermediates, any free compound and its salts mentioned above and below are of course also Include equivalent salts and free compounds (where appropriate and convenient). This paper size applies to China National Standard (CNS) A4 specification (2IOX297). 472057

Produced by the staff of the Central Bureau of Standards of the Ministry of Economic Affairs for consumer cooperation. Du V. Description of the invention () The compound of formula (I) has valuable pharmacologically useful properties. In particular, they exhibit specific inhibitory activity that is pharmacologically important. They are particularly effective inhibitors of tyrosine protein kinases and / or (further) inhibitors of serine / hydroxybutyrate protein kinases; they, for example, effectively inhibit the receptors of epidermal growth factor (EGF) And tyrosine kinase activity of oerbB2 kinase. Those receptor-specific enzyme activities play a key role in the signaling of many mammalian cells (including human cells), especially epithelial cells, immune system cells, and central and peripheral nervous system cells. For example, in various cell types, EGF-induced activation of receptor-associated tyrosine protein kinase (EGF-R-TPK) is a necessary condition for cell division and cell proliferation. Therefore, an increase in the number of 'EGF-receptor-specific tyrosine kinase inhibitors inhibits cell proliferation. The same applies to the other protein kinases mentioned above and below. In addition to inhibiting EGF-receptor tyrosine protein kinase, the compounds of formula (I) also inhibit to varying degrees other tyrosine protein kinases involved in the transmission of trophic factor mediators, such as abl kinase, especially v-abl kinase, Kinases from the src kinase family, in particular (; _ La kinase, ick, fine, other kinases of the EGF family (such as c-erbB2 kinase (HER-2), c-erbB3 kinase, c-erbB4 kinase, O'PDGF- Member of the receptor tyrosine protein kinase family (eg PDGF-receptor kinase, CSF-1 receptor kinase, Kit-receptor kinase, VEGF-receptor kinase (such as KDR and Flt-1)) and FGF-receptor kinase ), Insulin-like growth factor receptor kinases (IGF-1 kinases) and serine / hydroxybutyric acid kinases (such as protein kinase C or cdc kinase), all kinases grow in mammalian cells (including human cells) It plays a part in the adjustment and transformation. (Please read the notes on the back before filling in this page.) The size of the paper is applicable to the Chinese National Standard (CNS) M specification (210X 297 mm) -10- 472057 Central Ministry of Economic Affairs Printed by the Bureau of Standards Consumer Cooperatives A7 B7 Five Description of the invention () The inhibitory effect of EGF-receptor-specific tyrosine protein kinase (EGF-R-TPK) can be confirmed by known methods, such as the intracellular region of the EGF-receptor using genetic recombination (EGF-RICD See, for example, E. McGlynn et al., Europ. J. Biochem. 207, 265-275 (1992)). Compared to a control group without an inhibitor, the compound of formula (I) can inhibit enzyme activity by 50% ( IC5.), For example, at a concentration of 0.0005 to 1 μM, especially 0.001 to 0.1 μM. The effect of compounds of formula (I) on EGF-stimulated cellular tyrosine phosphorylation in EGF-receptors may be in human A431 Epithelial cancer cell lines were measured using an enzyme-linked immunosorbent assay (ELISA) described in ϋ. Trinks et al., J. Med. Chem. 37 ^, 1015-1027 (1994). In this test (EGFR-EUSA ), The compound of formula 展现 exhibits an IC5. 値 is about 0.001 to 1 μM. Stimulation of resting BALB / C3T3 cells with EGF can rapidly induce the expression of c-fos mRNA. Cells are pre-stimulated with compounds of formula (I) before being stimulated with EGF Treatment can inhibit c-fos performance at an IC5Q of about 0.001 to 0.1 μM. This test procedure is also described in U. Trink et al., J. Med. Chem. 37 ^ 7, 1015-1027 (1994). In the micromolar range, compounds of formula (I) also inhibit, for example, cell growth of EGF-dependent cell lines, such as the epidermal BALB / c murine keratinocyte line (see Weissmann, BA, and Aaronson, SA, Cell 32 , 599 (1983)) or A431 cell line, which has been identified as a standard source of useful EGF-dependent epithelial cells (see Carpenter, G., and Zendegni, J. Anal. Biochem. 153, 279 · 282 (1985) ). In a known test method (see Meyer et al., Int. J. Cancer 43, 851 (1989)), the inhibitory activity of a compound of formula (I) is simply determined as follows: BALB / MK cells (10,000 / micro) Titration plate wells) to a 96-well microtiter plate. Add a series of concentrations (diluent series) to test. The paper size is applicable to the Chinese National Standard (CNS) Λ4 specification (2 丨 〇X 297). (Please read the precautions on the back before filling out this page.) Order 472057 A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention () Compound (dissolved in dimethyl sulfoxide (DMSO)), added in such a way that the final concentration of dimethyl sulfoxide does not exceed 1% (volume /volume). After the addition, the plates were cultured for three days. During the culture, the control culture containing no test compound could undergo at least three cycles of cell division. The growth of MK cells was determined using methyl blue staining. After culture, the cells were fixed with glutaraldehyde, washed with water, and stained with 0.05% methyl blue. After rinsing, the dyed matter was eluted with 3% HC1 and the optical density of each microtiter plate well was measured using a Titertek Multiskan instrument at 665 dust meters. IC5. The system is determined using a computer-aided system, using the following formula: iCso = [(OD micro-group-0D from Kina) / (OD control group-0D from the chick)] X 100. IC5 in those experiments.値 is defined as the concentration of the test compound that results in a cell count that is 50% less than the number of cells obtained using a control group without an inhibitor. The compound of formula (I) exhibits inhibitory activity in the micromolar range, for example, 1C5 () is about 0.1 to 1 μM. The compound of formula (I) also exhibits tumor growth inhibition in vivo, as shown in the following test: The test is based on the growth inhibition (ATCC) of human epidermal carcinoma A431 implanted into female BALB / c hairless mice (Bomholtgard, Denmark) No. CRL 1555; American Type Culture Collection, Rockville, Maryland ^ United States; see Saftton ^ JB, et. Al., Cancer Research 46, 47Q1-4705 (1986) and Ozawa ^ S., et al ., Int. J. Cancer 40, 706-710 (198 Nai). This cancer exhibits growth, which is related to the degree of expression of the EGF_receptor. In experiments, tumors of approximately 1 cubic centimeter volume were cultured in vivo. Removal from laboratory animals under sterile conditions. The tumor was pulverized and suspended in 10 volumes (weight / volume) of phosphate buffered saline. Suspended (please read the precautions on the back before filling this page) This paper size applies China National Standard (CNS) A4 specification (2I0X297 mm) -12- 472057 Central Standard of the Ministry of Economic Affairs, printed by employee consumer cooperatives A7 B7 V. Description of the invention () Liquid percutaneous (0.2ml / rat, in phosphorus Saline buffered saline) into the left peritoneum of the animal. Alternatively, IX 106 cells taken from in vitro culture (in 0.2 ml phosphate buffered saline) are injected. 5 or 7 days after transplantation When the tumor diameter reaches 4-5 mm, treatment with the test compound of formula (I) is started. The test compound is injected once a day for 15 consecutive days (different doses for different animal groups). Tumor growth lines are used along three The method of measuring the diameter of the tumor in the axial direction perpendicular to each other is determined. The tumor volume is calculated using the known formula p XLX D2 / 6 (see Evans, BD "et al" Brit. J · Cancer 45, 466 ~ 8 (1982). Results Expressed as the percentage of treatment / control (T / C x 100 = T / C%). At a dose of 3 to 50 mg / kg active ingredient, significant tumor growth inhibition is found, for example, T / C% 値 is less than 10 In addition to inhibiting EGF-receptor tyrosine protein kinase, compounds of formula (I) also inhibit other tyrosine protein kinases involved in the transmission of nutrient factor mediators, such as abl kinase, especially like v-abl kinase (Such as IC5e 値 from 0.01 to 5 μM), kinases from the src kinase family, especially c-src kinases (such as IC50 値 from 0.1 to 10 μM), c-erbB2 kinase (HER-2), and seramine Acid / hydroxybutyric acid kinases (such as protein kinase C), all kinases are involved in the growth regulation and transformation of mammalian cells (including human cells). The above-mentioned inhibition of v-abl tyrosine kinase was determined by the method of N. Lydon et al. (Oncogene Research 5, 161-173 (1990) and JF Geissler et al., Cancer Research 52, 4492-4498 (1992). In those methods, [Val5] -angiotensin II and [γ-32P] -ATP were used as the substrates. This paper size applies the Chinese National Standard (CNS) Λ4 specification (2 丨 〇 × 297) ) I 1; «11-----........ 11- I -II ——-k 1. Install --- (Please read the precautions on the back before filling this page) ίτ — ^ ----- -13-472057 A7 B7 V. Explanation of the invention () c-erbB2 tyrosine kinase (HER-2) can be inhibited, for example, the method similar to that used by EGF-R-TPK Assay (see C. House et al., Europ. J. Biochem. 140, 363-367 (1984)). The c-erbB2 kinase can be isolated using protocols known per se and its activity can be determined, for example according to T. Akiyamaetal ., Science 232, 1644 (1986). Therefore, compounds of formula (I) that inhibit the tyrosine kinase activity of the epidermal growth factor (EGF) receptor or the tyrosine kinase activity of the other tyrosine protein kinases previously described It is useful, for example, in the treatment of benign or malignant tumors. It can achieve the purpose of tumor degeneration and prevent the formation of tumor metastases and the growth of micrometastases. It is particularly useful in cases of high epidermal proliferation (psoriasis), treatment of tumor formation of epithelial properties ( Such as breast cancer) and the treatment of leukemia. In addition, compounds of formula (I) (especially novel compounds) can be used to treat those disorders of the immune system involving several or especially individual tyrosine protein kinases and / or (more advanced ) Serine / hydroxybutyrate protein kinases; those compounds of formula (I) can also be used to treat those disorders of the central or peripheral nervous system, involving several or especially individual tyrosine protein kinases and / or (more (Promoter) Signal transmission of serine / hydroxybutyric acid protein kinase. Printed by the Consumer Co-operation of the Central Standards Bureau of the Ministry of Economic Affairs (please read the notes on the back before filling this page). Generally, the present invention also relates to compounds of formula ⑴ Use in inhibiting the aforementioned protein kinases. The compounds of the present invention can be used alone or together with other pharmacologically active compounds, for example For example, together with inhibitors of polyamine synthase, inhibitors of protein kinase C, other inhibitors of tyrosine, cytokines, negative growth regulators (e.g. tgf_psifn_p), aromatase inhibitors, anti-estrogens and / or inhibitory cells Drugs. This paper size is applicable to China National Standards (CNS) Λ4 specifications (210 X2 ^ 7 public release) -14- 472057 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs · Β7_5 Description of Inventions () are mentioned below In the preferred subject matter of the invention, where appropriate and convenient, general definitions may be replaced by more specific definitions given at the outset. Preference is given to compounds of the formula 及其 and their salts, where q is 0 or 1, η is 1 to 3 (when q is 0), or η is 0 to 3 (when q is 1), and R is a halogen, lower alkane Base, hydroxy, lower alkoxy, lower alkoxy, carboxyl, lower alkoxycarbonyl, carbamoyl, N-lower alkyl-carbamoyl, N, N-di-lower amine-carbamoyl, Cyano, amine, lower alkylamino, lower alkylamino, N, N-di-lower alkylamino or trifluoromethyl, when there are several radicals R in the molecule, these radicals can be the same or They are different and are independent of each other. They are carbamoyl-methoxy, carboxy-methoxy, benzyloxy-methoxy, lower alkoxy curtain-methoxy, phenyl, amino, lower alkylamino, Lower alkylamino, N, N-di-lower alkylamino, hydroxyl, lower alkoxy, carboxyl, lower alkoxycarbonyl, carbamoyl, N-lower alkylaminocarbamyl, N, N-di Lower grades-carbamoyl, cyano or nitro substituted phenyl, hydrogen, unsubstituted or substituted with halo or lower alkyl, pyridyl, N-node-D-pyridin-2-yl, naphthalene Cyano, cyano, carboxyl, lower alkoxycarbonyl, carbamate Fluorenyl, N-lower compound-carbamyl, N, N-di-lower compound-carbamyl, N-benzyl-carbamyl, formamyl, lower alkylsulfonyl, lower alkenyl, lower alkenyl Oxygen, or halogen, amine, lower alkylamino, hexahydropyridyl, di-lower alkylamino, hydroxyl, lower alkoxy, cyano, carboxyl, lower alkoxycarbonyl, carbamoyl, N_ Lower alkane · carbamoyl, N, N-di-lower alkane-carbamoyl, fluorenyl, or a radical of the formula r3-S (〇) m- (where R3 is lower alkyl and m is 0, 1 or 2) Replaced low-grade base, or this paper size applies Chinese National Standard (CNS) Λ4 specification (2! 0X 297 mm) ----: ------ install -----,-order- -* ---- (Please read the notes on the back before filling out this page) -15-Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 472057 Λ7 B7 V. Description of the invention () b) When q is 0, free radicals one of & and 112 is an unsubstituted lower alkyl group or an unsubstituted phenyl group, and the other of the radicals 1 ^ and 112 has the meaning specified in a) above, or magic and private Amines, lower amines, lower amines Group, n, N-di-lower alkylamino, nitro, halogen, hydroxyl, lower alkanoyloxy, carboxyl, lower alkoxycarbonyl, carbamate, N-lower house · carbamate, N, N -Secondary lower grade-carbamoyl or cyano-substituted CrC1 ()-1,4-alkylene dienyl, or Πα-l, 4-alkylene dienyl having up to 9 carbon atoms , Or d) when q is 1, private and & are independent, and are unsubstituted lower alkyl or unsubstituted phenyl, or have the meaning specified in a) above, and K is hydrogen, lower Alkyl, lower alkoxycarbonyl, carbamoyl, N_lower alkyl-carbamoyl, or N, N-di-lower alkyl-carbamoyl, and η in formula 0) is 0, q is 1, That is, except for compounds in which each is hydrogen and & is methyl. Preferred compounds are also compounds of formula (I) and their salts, where q is 0 or η is 1 to 3 (when q is 0), or η is 0 to 3 (when q is 1), and R is a dentin. , Lower alkyl, hydroxyl, lower alkoxy, lower alkoxy, carboxyl, lower alkoxycarbonyl, carbamoyl, N-lower alkane-aminomethyl, N, N-di-lower home Fluorenyl, cyano, amine, lower alkylamino, lower alkylamino, N, N-di-lower alkylamino or trifluoromethyl. When there are several free radicals R in the molecule, these radicals can be Is the same or different, is hydrogen and R2 is amine formamidine-methoxy, carboxy-methoxy, benzyloxy-methoxy, lower alkoxycarbonyl-methoxy, phenyl, amine, lower alkyl醯 Amine-based, low-paper sizes are applicable to Chinese National Standards (CNS) Λ4 specifications (2 丨 OX297 male and male) -------- •• Installation ----- Γ Order-,, ----- (Please read the precautions on the back before filling this page) -16- 472057 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention () Grade alkylamino, N, N-di-lower alkylamine, Hydroxyl, lower alkoxy, carboxy, lower alkoxy Phenyl, carbamoyl, N-lower alkyl-carbamoyl 'RN-di-lower alkyl-carbamoyl, cyano or nitro substituted phenyl, unsubstituted or halogenated or lower alkyl Pyridyl, N-benzyl-2-yl, naphthyl, cyano, carboxyl, lower alkoxycarbonyl, carbamate, N-lower alkyl-carbamate, N, N-di-lower Amino-aminomethylamino, Nf-aminomethylamino, methylamino, lower alkylamino, lower alkenyl, lower alkenyloxy, or halogen, aniline (which is unsubstituted or substituted in the phenyl moiety Halogen, lower alkyl, hydroxy, lower alkoxy, lower alkoxy, carboxyl, lower alkoxycarbonyl, carbamoyl, N-lower alkane-aminomethyl, N, N-di-lower alkane-amine (Formyl or trifluoromethyl substituted), lower alkoxy, cyano, carboxyl, lower alkoxycarbonyl, carbamoyl, N-lower alkyl-aminoformyl, N, N-di-lower amine Formamyl, fluorenyl or a radical of the formula R3-S (0) „r (where R3 is a lower alkyl group and m is 0, 1 or 2) substituted lower alkyl group, or b) when q is 0, free One of the radicals & is unsubstituted lower alkyl or Unsubstituted phenyl, and the other of the radicals and private has one of the meanings specified in a) above (other than hydrogen), or (^ & together with ^ is a lower alkylamino, Nitro, halide, carboxyl, lower alkoxycarbonyl, carbamate, N-lower house-carbamate, N, N-lower house-carbamate or cyano substituted C4-C1 (rl , 4 · alkanedienyl, or ηγ-ι, 4-alkanedienyl, having up to 9 carbon atoms, or d) When q is 1, R is hydrogen and R2 is unsubstituted Phenyl, and R6 are hydrogen, lower alkyl, lower alkoxycarbonyl, carbamoyl, N-lower alkyl-carbamoyl, or N, N-di-lower alkyl-carbamoyl. This paper size applies to China National Standards (CNS) Λ4 specifications (2 丨 OX 297 mm) (Please read the notes on the back before filling this page) 've Γ -17- 472057 A7 B7 V. Description of the invention (preferred selection) 7H-B pyrrolidine [2,3-d] pyrimidine derivative and its salt of formula (la)

(la) Printed by the Consumer Standards Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs (la) where η is 1 to 3, and R is a tooth element, a lower alkyl group, a hydroxyl group, a lower alkoxy group, a lower alkoxy group, a carboxyl group, and a lower alkyl group. Oxycarbonyl, carbamoyl, N-lower alkyl-carbamoyl, Ν, Ν-di-lower amine · carbamoyl, cyano, amine, lower alkylamino, lower alkylamino, N, N-di-lower alkylamino or trifluoromethyl, when there are several radicals R in the molecule, these radicals may be the same or different, a) & and each are independent, are phenyl, amine, Lower alkyl acid amine, lower alkyl amine, N, N-di-lower alkyl amine, hydroxyl, lower alkoxy, carboxyl, lower oxo carbonyl, carbamoyl, N-lower amine-carbamyl , N, N-di-lower alkyl-carbamoyl, cyano or nitro substituted phenyl, hydrogen, unsubstituted or pyridyl substituted with halo or lower alkyl, N-Section 4b 2-yl, naphthyl, cyano, carboxyl, lower alkoxycarbonyl, carbamoyl, N-lower alkane-carbamyl, N, N-di-lower compound-carbamoyl, formamyl, lower Alkyl, lower alkenes Base, lower alkenyloxy, or halogen, amine, lower alkylamino, hexahydropyridyl, dilower alkylamino, hydroxyl, lower alkoxy, cyano, carboxyl, lower alkoxycarbonyl, aminomethyl Fluorenyl, N-lower compound-carbamoyl, N, N · di-lower compound-carbamoyl, aryl, or radicals of the formula R3-S (0) m- (where 仏 is lower alkyl and m 0, 1 or 2) substituted lower alkyl, or (please read the notes on the back before filling out this page) -T •-° 4 This paper size is applicable to the Chinese National Standard (CNS) Λ4 specification (2 丨 〇 ' (〆297 mm) 472057 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention () b) One of the radicals & 112 is an unsubstituted lower alkyl or unsubstituted phenyl And the other of the radicals and fluorene has one of the meanings specified in a) above (apart from hydrogen), or (〇 & together with a private amino group, a lower alkylamine group, a lower alkylamine Base, N, N-di-lower alkylamino, nitro, halide, hydroxyl, lower alkanoyloxy, carboxyl, lower alkoxycarbonyl, carbamate, N-lower compound -Carbamoyl, N, N-di-lower compound-carbamoyl or cyano-substituted C4-C1 (rl, 4-alkylene dienyl, or H-ha with up to 9 carbon atoms- 1,4-alkylene dienyl. Very particular preference is given to compounds of formula (I) and their salts, where η is 1 to 3 and q is 0, and R is halogen, lower alkyl, hydroxyl, lower alkyl Oxy, lower alkoxy, carboxyl, lower alkoxycarbonyl, carbamoyl, N-lower alkyl-carbamoyl, N, N-di-lower amine-carbamoyl, cyano, amine, lower Alkylamino, lower alkylamino, N, N-di-lower alkylamino or trifluoromethyl, when there are several radicals R in the molecule, these radicals may be the same or different, and 3) & And 112 are each independently phenyl, amine, lower alkylamino, lower alkylamino, N, N-di-lower alkylamino, hydroxyl, lower alkyloxy, carboxyl, lower alkoxycarbonyl, amine Formamyl, N-lower amidine-aminoformamyl, N, N.-lower amidine-aminoformamyl, cyano or nitro substituted phenyl, unsubstituted or substituted with halo or lower alkyl Pyridyl, N-segment-fluoride_2-yl, naphthyl, Group, carboxyl group, lower alkoxycarbonyl group, carbamoyl group, N-lower alkane-carbamyl group, Ν, Ν-di-lower amine · carbamyl group, formamyl group, lower alkynyl group, lower alkenyl group, Lower alkenyloxy, or halogen, amine, lower alkylamino, hexahydropyridyl, di-lower alkylamino, hydroxyl, lower alkoxy, cyano, carboxyl, This paper is in accordance with Chinese national standards (CNS ) Α4 specification (2 丨 0 × 297 mm) I ------- · Installation ----- Γ Order-«----- (Please read the precautions on the back before filling this page)- 19- 472057 Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs Β7. V. Description of the invention () Lower alkoxycarbonyl, carbamoyl, N-lower alkane · carbamyl, N, N-di-lower institute-amine Formamyl, fluorenyl or radicals of the formula R3-S (0) m- (wherein R3 is lower alkyl and m is 0, 1 or 2) substituted lower alkyl, or b) radical & and 112 One of them is hydrogen, an unsubstituted lower alkyl group or an unsubstituted phenyl group, and the other of the radicals ^ and & has the meaning specified in a) above (apart from hydrogen), or &Amp; with & Amino, lower alkylamino, lower alkylamino, N, N-di-lower alkylamino, nitro, halogen, hydroxyl, lower alkyloxy, carboxyl, lower alkyloxycarbonyl, and carbamate , N-lower home-carbamyl, N, N-lower home-carbamyl or cyano-substituted C4-Cw-1,4 · alkanedienyl, or up to 9 carbons Atomium yah-1,4-alkanedienyl. Particularly preferred are compounds of formula (I) and their salts, where η is 1 or 2 and q is 0, and R is a halogen. When there are several radicals R in the molecule, these radicals may be the same or different. And 3) & and & are each independently a phenyl group substituted with a phenyl group, an amine group, a hydroxyl group, or a nitro group, a hydrogen group, a pyridyl group, a NfU group-2-yl group, a naphthyl group, or a di-lower alkane Amino-substituted lower alkyl, or b) one of radicals 1 ^ and 112 is an unsubstituted lower alkyl or unsubstituted phenyl, and the other of radicals 1 and 2 has a ), In addition to hydrogen, or 幻 &仏; together with 仏 is a Π-1,4-alkanedienyl group having up to 9 carbon atoms. Particularly preferred are the compounds of formula (I) and their salts, where η is 1 or 2 and q is 0. The paper size applies to the Chinese National Standard (CNS) A4 specification (2 丨 0X297 mm) (please read the back first) Please pay attention to this page and fill in this page) ^ clothing · d -20- 472057 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention () R is halogen. When there are several free radicals R in the molecule, these The radicals may be the same or different, and a) Ri is hydrogen, or an unsubstituted or lower alkyl group substituted with a di-lower alkylamino group, and ^ is a benzene substituted with a phenyl, amine, hydroxyl, or nitro group The group is pyridyl, N-stilbene-2-yl, or naphthyl, or stilbene together with stilbene is π-1,4-alkanedienyl having up to 9 carbon atoms. Preferred are also compounds of formula (I) and their salts, where q is 1, η is 0 to 3, and R is halogen, lower alkyl, hydroxy, lower alkoxy, lower alkoxy, carboxy, lower Alkoxycarbonyl, carbamoyl, N-lower alkyl-carbamoyl, N, N-di-lower alkyl-carbamoyl, cyano, amine, lower alkylamino, lower alkylamino, Ν , N-di-lower alkylamino or trifluoromethyl, when there are several free radicals R in the molecule, these free radicals may be the same or different, 3) Za and 112 are independent, and they are methano-methoxy Base, Jun-methoxy, benzyloxy curtain · methoxy, lower alkoxymethoxy, phenyl, amine, lower alkylamino, lower alkylamino, Ν, Ν-di-lower alkylamino, Substituted by hydroxyl, lower alkoxy, carboxy, lower alkoxycarbonyl, carbamoyl, N-lower alkyl-carbamoyl, N, N-di-lower alkyl-carbamoyl, cyano or nitro substituted Phenyl is hydrogen, pyridinyl, unsubstituted or substituted with halo or lower alkyl, N-benzyl-pyridin-2-yl, naphthyl, cyano, endyl, lower alkoxycarbonyl, amine Formamyl, NR-lower school- Formamyl, N, N-di-lower amine-aminoformamyl, N-benzyl-aminoformamyl, formamyl, lower alkylamyl, lower alkenyl, lower alkenyloxy, or halogen, amine , Lower alkylamine, hexahydropyridyl, di-lower alkylamine This paper applies the Chinese National Standard (CNS) A4 specification (21〇 × 297 cm) (Please read the precautions on the back before filling this page) -β Γ -21-472057 Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs A7 B7 V. Description of the invention () Group, hydroxyl, lower alkoxy, cyano, carboxyl, lower alkoxycarbonyl, carbamate, N-lower Fluorenyl-carbamoyl, N, N-di-lower compound-carbamoyl, fluorenyl or a radical of the formula RrSWk- (where R3 is lower alkyl and m is 0, 1 or 2) substituted lower alkyl , Or 1 >) 111 together with & are amine, lower alkylamino, lower alkylamino, N, N-di-lower alkylamino, nitro, dentin, hydroxyl, lower alkyloxy, Carboxyl, lower alkoxycarbonyl, carbamoyl, N-lower carbamoyl, N, N-di-lower melamine-carbamoyl, or cyano-substituted C4_C1 (rl, 4-butanediene Group, or U-I-1,4-alkanedienyl group with up to 9 carbon atoms, or p & and 112 are each independently unsubstituted lower alkyl or unsubstituted phenyl, or Has one of the meanings specified in a) above, and Re is hydrogen, lower alkyl, lower alkoxycarbonyl, carbamoyl, N-lower alkyl-carbamoyl, or N, N-di-lower compound-amine醯 基. Particularly preferred are also compounds of formula (I) and their salts, where 9 is 0 or 1, η is 1 to 2 (when q is 0), or η is 0 to 2 (when q is 1), and R is Halogen or lower alkyl, when several radicals R are present in the molecule, these radicals may be the same or different, and a) lower alkyl which is hydrogen or unsubstituted or substituted with a di-lower alkylamine group, And R2 are carbamoylmethoxy, carboxymethoxy, benzyloxycarbonylmethoxy, lower alkoxycarbonylmethoxy, lower alkoxycarbonyl, carboxyl, N, N-di-lower compound-aminoformyl , Phenyl, amine, lower alkylamino, di-lower alkylamino, lower alkylamino, hydroxy or nitro substituted phenyl, hydroxy-lower alkyl, amine-lower alkyl, di-lower alkylamine · Lower alkyl, hexahydropyridine-lower alkyl, methyl form This paper is also applicable to China National Standard (CNS) A4 (210X297 mm) n In ^ in In HI In —1 nn ^ i It In 1 ^ 1 1 ^ .1 ml m · m · (Please read the precautions on the back before filling this page) -22- 472057 Printed by the Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention () Basic, cyanide base, Base, lower alkoxycarbonyl, carbamate, NMδ-grade amine-carbamoyl, Ν, Ν- di-lower-grade carbamoyl, pyridyl, Ν · -carbamidine, Ν-benzyl- D is more than 2-yenyl or naphthyl, or b) is a 1-Πγ-butane-1,3-bis--1,4-yl, or c) when q is 1, And 112 are each methyl, and Re is hydrogen, methyl, or lower alkoxycarbonyl. Particularly preferred are also compounds of formula (I) and their salts, where q is 0 or η is 1 to 2 (when q is 0), or η is 0 to 2 (when q is 1), and R is halogen When there are several free radicals R in the molecule, these radicals may be the same or different, and a) a lower alkyl group which is hydrogen or unsubstituted or substituted with a di-lower alkylamino group, and R2 is substituted by an amine Formamylmethoxy, carboxymethoxy, benzyloxycarbonylmethoxy, methoxycarbonylmethoxy, ethoxycarbonyl, carboxy, phenyl, amine, acetamido, hydroxy or nitro substituted phenyl Is a carboxyl, ethoxycarbonyl, ^ M-grade carbamoyl group, pyridyl, N-section 4 than indan-2-yl or naphthyl, or 111 and 112, up to 9 carbons When the atom is 0-1,4-alkadienyl, or c) when q is 1, each is methyl, and the core is hydrogen, methyl, or lower alkoxycarbonyl. Preference is given in particular to the compounds of formula (I) and their pharmaceutically acceptable salts as described in the examples. The present invention also relates to the compound 4- (3-chloro ·· aniline) -pyrimidine hydrazone [4,5-b] indole (which is not within the scope of formula (I), and is obtained according to Example (Reference Example) I5 ) And its pharmaceutically acceptable salts. This paper size applies Chinese National Standard (CNS) Λ4 specification (210 × 297 mm) (Please read the precautions on the back before filling this page) ^ —, 1τ .4 -23- 472057

A7 B7 5. Description of the invention () The compound of formula (I) and its salts are prepared by a method known per se. The method of the present invention includes a) a pyrrolidine [2,3-d] pyrimidine derivative (II) of formula (II) (wherein X is a suitable leaving group, and Z is hydrogen or 1-aryl- Lower alkyl and other substituents are as defined for the compound of formula (I) above, and if necessary, any free functional group present in radicals 1 ^ and R2 is protected by an easily removable protecting group) and reacted with an amine of formula (III) , --------- 0. (Please read the precautions on the back before filling this page) -Install. (R) n

(CHRe) —N (ΠΙ) • -Order Printed by the Central Consumers ’Cooperative of the Ministry of Economy

(R, R ^, η and q in the formula (III) are as defined for the compound of the formula (I) above, and if necessary, any free functional group present in the radical R is protected by a protective group that can be easily removed), and any existing Protecting group and (in the presence of) 1-aryl_lower alkyl radical Z, or b) in the presence of a dehydrating agent and a third amine, a pyrrolidine [2,3-d] pyrimidine of formula (IV)- 4-Xing derivatives (IV) (Z 'in formula (IV) is 1-aryl-lower alkyl, & and 112 are as defined for the compound of formula (I) above, if necessary, radicals & and & Any free functional groups that exist are printed by the Chinese standard (CNS) Λ4 specification (210X297 gigabytes) of this paper size -24- 472057 A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention () Easy to remove protection Group protection) with one or more amines of the formula (ΠΪ) and removing any existing protecting groups, or c) preparing a compound of the formula (wherein dimethylamine-methyl and the remaining substituents are the compounds of the formula 以上) When it is defined, a compound corresponding to formula (I) (wherein & is hydrogen and the remaining substituents is as shown in formula (I) above The definition of the substance, when necessary, the free radicals and protectors of any free functional groups that are easily removed in the heart are protected by protective groups) and tritiated N, N-dimethyl-methyleneimmonium, and remove any existing protective groups Or d) when preparing a compound of the formula "I" (wherein at least one of the radicals R, 1 ^ and 2 is a phenyl group substituted by a hydroxyl group, and the remaining substituents are as defined for the compound of formula (I) above), A compound corresponding to the formula (1) (wherein at least one of the radicals R, P, and 112 is a phenyl group substituted by methoxy, and the remaining substituents are as defined for the compound of formula (I) above. R, protector of any free functional group that is easily removed in the protection group) reacts with boron tribromide and removes any protective group present, or e) prepare a compound of formula (I) (at least one of which is free When R, Xin and & 2 are phenyl substituted by amine, and the remaining substituents are as defined above for the compound of formula (I), a compound corresponding to formula φ (at least one of which is a radical R, Gen and & are phenyl substituted by nitro, and the rest The radical is as defined for the compound of formula ① above, and if necessary, any free functional groups present in the radicals R, & and Di 2 are protected by an easily removable protective group), and the protective group is removed by catalytic removal, (please First read the notes on the back „1 · Item and fill in. Pack —: Write this page)-Order Φ This paper size applies to Chinese National Standard (CNS) A4 (2IOX297 mm) -25-472057 A7 B7 V. Description of the invention () And after implementing one of the methods a) to e), when it is necessary to prepare a salt, the 2 Θ (I) 2 free compound is converted into a salt, or when it is necessary to prepare a free compound, 'formula (I) will be formed Compound salts are converted into free compounds. The above method steps are detailed below (see also German Patent Case No. 3036390, published on May 13, 1982, and A. Jorgensen et al., J. Heterocycl. Chem. 22, 859 [1985]). In the following more detailed description, unless otherwise specified, ' R, & and 112 and η are as defined for a compound of formula (I). General points: The end product of formula (I) may contain substituents and it may also be used as a protecting group in the starting materials for the preparation of other end products of formula (I). Unless otherwise stated herein, the term " protecting group " as used herein only represents an easily removable base and is not a constituent of a particular desired end product of formula (I). Method a) In the compounds of formula (Π), the appropriate leaving group X is preferably a halogen such as bromine, iodine or especially chlorine. The 1-aryl-lower alkyl z is preferably 1-benzene-lower alkyl, such as particularly 1-phenethyl or more particularly benzyl. Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs (please read the precautions on the back before filling this page) Free radicals & and free functional groups present in 112 (protected by an easily removable protective group if necessary), especially amines Or lower alkylamino. Protective groups and their introduction and removal are described in, for example, " Protective Groups in Organic Chemistry ", Plenum Press, London ^ New York 1973 & " Methoden der organischen Chemie ", Houben-Weyl, 4th edition, Vol. 15/1 Georg-Thieme-Verlag ^ Stuttgart 1974 and Theodora W. Greene, " Protective Groups in Organic Synthesis ", John Wiley & Sons, New York 1981. The protective paper's special paper scale is applicable to the Chinese National Standard (CNS) Λ4 specification (210X297 mm) -26- Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 472057 A7 B7____ 5. Description of the invention () It can be easily removed ( That is, unwanted side reactions do not occur), such as the use of solvolysis, reduction, photolysis or under physiological conditions. The protected amine group may exist, for example, in the form of a cleavable sulfonylamino group, an arylmethylamine group, an etherified sulfonylamine group, or a 2-acidylamino group. In this monoamine group, the fluorenyl group is a fluorenyl radical of an organic carboxylic acid having, for example, up to 18 carbon atoms, especially an unsubstituted or substituted (for example, substituted by a radical or an aryl group) Alkyl carboxylic acids are either unsubstituted or substituted (eg, substituted with halo, lower alkoxy, or nitro) fluorenyl radicals of benzoic acid, or fluorenyl radicals of half carbonate. This alkynyl group is, for example, a lower alkylfluorenyl group (such as methylamino, ethylfluorenyl, or propionyl), a halogen-lower alkylfluorenyl group (such as 2-haloethylfluorenyl, especially 2-chloro-, 2- Bromo-, 2-iodo-, 2,2,2-trifluoro- or 2,2,2, trichloro · ethylfluorenyl), unsubstituted or substituted (for example, dentyl, lower alkoxy Or nitro-substituted) benzamidine (such as benzamidine, 4-chlorobenzyl, 4-methoxybenzyl, or 4-nitrobenzyl), or a component at the 1-position of a lower alkyl radical Branch or lower alkoxycarbonyl group appropriately substituted at the 1- or 2-position, especially a third lower alkoxycarbonyl group (such as a third butoxycarbonyl group), an arylmethoxycarbonyl group having one or two aryl radicals (aryl The radical is preferably an unsubstituted or mono- or poly-substituted phenyl group, such as a lower alkyl group, especially a third lower alkyl group (like a third butyl group), a lower alkoxy group (like a methoxy group), Hydroxyl, halogen (such as chlorine) and / or nitro-substituted phenyl), like unsubstituted or substituted benzyloxycarbonyl (such as 4-nitrobenzyloxycarbonyl) or substituted diphenyloxycarbonyl (such as Dibenzomethoxycarbonyl or di (4-methoxybenzene Methoxycarbonyl), aryl methoxymethyl, of which the aryl fluorenyl group is preferably a benzyl group, which is unsubstituted or substituted, such as by halogen (such as bromine) (such as benzyloxycarbonyl), 2-benzyl Paper size is applicable to China National Standard (CNS) A4 specification (210X297 male Jie) -------- 0 Pack ----- > 1 · Order: ------ Φ. (Please read the back first Please pay attention to this page, please fill in this page) -27- Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs 472057 A7 B7 V. Description of the invention () Country-grade alkoxycarbonyl (such as 2,2,2-trichloroethoxycarbonyl) , 2-bromoethoxycarbonyl or 2-iodoethoxycarbonyl), or 2- (trisubstituted silyl group)> ethoxycarbonylsulfonium, wherein the substituents are independent of each other, and are unsubstituted with up to 15 carbon atoms. Substituted or substituted (for example, by lower alkyl, lower alkoxy, aryl, halo, or nitro) aliphatic-, aralipha-, cycloaliphatic-, or aromatic hydrocarbon radicals, as equivalent Substituted or substituted lower alkyl, benzene_lower alkyl, cycloalkyl, or phenyl, such as 2-tri-lower-silicon-silylethoxycarbonyl (like 2-trimethylsilylethoxy- or 2- ( Di Zhengding- · Silicon Academy) ethoxycarbonyl), or 2-triarylsilane ethoxycarbonyl (like 2-triphenylsilane ethoxycarbonyl). In arylmethylamino (which is mono-, di-, or especially tri-arylmethylamine) In the group), aryl radicals are in particular unsubstituted or substituted phenyl radicals. This group is, for example, m-, dibenzyl, and especially triphenyl-amine. Protected amine The etherified fluorenyl group is particularly an arylthio group or an aryl-lower alkylthio group, in which the aryl group is particularly an unsubstituted or substituted phenyl group, such as a lower alkyl group (such as methyl or a third butyl group). ), Lower alkoxy (like methoxy), halogen (like chlorine), and / or nitro-substituted phenyl. The equivalent amine protecting group is, for example, 4-nitrophenylthio. In 2-amino-lower can-1-yl radicals that can be used as amine protecting groups, the fluorenyl group is' e.g., a fairly free radical of a lower alkanecarboxylic acid, unsubstituted or substituted (e.g., by a lower Equivalent free radicals of alkyl (like methyl or third butyl), lower alkoxy (like methoxy), halogen (like chlorine) and / or nitro substituted or benzoic acid half (like Carbonyl lower alkyl half ester) is quite free radical. The equivalent protective group is μ lower alkyl alkene · propene _2. The basic paper size is applicable to China National Standard (CNS) A4 specification (2IOX297 cm) ---------— mu n I nn * 、 5 hearts — ^ n —4—— · 1 · 11 n # (Please read the notes on the back before filling out this page) -28- 472057 A7 B7 Printed by the Staff Consumer Cooperative of the Central Bureau of Standards, Ministry of Economic Affairs ) (Like 1-acetamidine-prop-1-can-2-yl) or 1-lower alkoxide-prop-1-an-2-yl (such as 1-ethoxycarbonyl-prop-1-ene-2 -base). Preferred amine protecting groups are the fluorenyl radicals of hemicarbonate, especially tertiary butoxycarbonyl, unsubstituted or substituted (as described above) benzyloxycarbonyl (such as 4-nitro-benzyloxycarbonyl) or Dibenzyloxycarbonyl, or 2-halo-lower alkoxycarbonyl (like 2,2,2-trichloroethoxycarbonyl) and trityl or formamyl. The reaction between the derivative of formula (II) and the amine of formula (III) takes place in a suitable inert polar solvent, in particular an alcohol such as a lower alkanol (like methanol, propanol, isopropanol or especially ethanol or n-butanol ). In some cases, it may be advantageous to add a solubilizing agent (such as 1,3-dimethyl-3,4,5,6-tetrahydro · 2 (1Η) -pyrimidone (DMPU)). The reaction takes place at a high temperature, for example in a temperature range from 70 to 150 ° C, preferably under reflux. If Z in the compound of formula (Π) is a 1-aryl-lower alkyl group, the radical is removed from the precursor of the compound of formula (I) (wherein Z is substituted for a hydrogen atom on the nitrogen). This is achieved, for example, by treatment with a protonic acid (such as hydrochloric acid, phosphoric acid or polyphosphoric acid) at a high temperature of 20 ° C to 150 ° C and, where appropriate, in the presence of water (its particular preference when Z = phenylethyl) Method); or preferably in an aromatic hydrocarbon solvent (especially benzene / or toluene) at high temperature (especially under reflux) and treated with a Lewis acid (especially A1C13) [when especially Z = benzyl Preferred method; see also Chem. Pharm. Bull. 39 (5), 1152 (1991) for a similar method]. The removal of the protective groups of the components of the undesired formula ⑴ end product is achieved by a method known per se, such as the use of solvolysis, especially water — «jut mm — ί nn VV, Jtii 4H n dn nn (Please first Read the notes on the reverse side and fill out this page) This paper size applies to Chinese National Standard (CNS) A4 specifications (2 丨 OX297g t) • 29- 472057 Employees' Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs, Printed Poly A7, V. Invention Description ( ) Hydrolysis, alcoholysis or acidolysis, or the use of reduction reactions, especially hydrogenolysis or chemical reduction, may be performed stepwise or simultaneously as appropriate. The protected amine hydrazone is released in various ways by a method known per se and according to the nature of the protecting group, and it is more appropriate to use a solvent decomposition or reduction reaction. 2-halo-lower alkoxycarbonylamino group (after conversion of 2-bromo-lower alkoxycarbonylamino group to 2-iodine · lower alkoxycarbonylamino group, if appropriate), arsenylmethoxycarbonylamino group or 4- Nitrobenzyloxycarbonyl can be cleaved, for example, by treatment with a suitable chemical reducing agent (like zinc) in the presence of a suitable carboxylic acid (like aqueous acetic acid). Aryl methoxycarbonylamide can also be cleavable with a nucleophile, more suitable for salt formation reagents (such as sodium thiophenolate) and split, and 4 · 5 Benzyloxycarbonylamino can also be used with an alkali metal dithiosulfinate Acid salt (such as sodium dithiosulfinate) to split. Unsubstituted or substituted dibenzyloxycarbonylamino, third lower alkoxycarbonylamino, or 2-trisubstituted silylethoxycarbonylamino may be treated with a suitable acid, such as formic acid or trifluoroacetic acid. And split; unsubstituted or substituted benzyloxycarbonyl can be split, for example, by hydrogenolysis, that is, split by treatment with hydrogen in the presence of a suitable hydrogenation catalyst (like a palladium catalyst); Substituted or substituted triarylmethylamine or formamidine can be used, for example, with an acid such as a mineral acid (e.g. hydrochloric acid) or an organic acid (e.g. formic acid, acetic acid or trifluoroacetic acid) in the presence of water where appropriate Cleavage by processing; and amine groups protected by an organosilyl group can be explained, for example, by hydrolysis or alcohol. An amine group protected by a 2-haloethylfluorenyl group (e.g., 2-chloroethylfluorenyl) can be treated with thiourea in the presence of a base, or a thiouric acid salt of a thiourea (such as a sulfonium metal thiolate) ) Treatment, followed by solvolysis (such as alcoholysis or hydrolysis) of the formed condensation product to release -------- install ----- Γ order -------- 9 (Please read the back first Please pay attention to this page and fill in this page again) This paper size applies Chinese National Standards (CNS) Λ4 specifications (2 丨 〇 < 2 () 7 males) -30- 472057 Employees' Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs print A7 B7 Fifth, the description of the invention (). An amine group protected by a 2-substituted silane ethoxycarbonyl group can also be converted to a free amine group using a hydrofluoric acid salt which generates a fluoride anion. Process b) The 1-aryl-lower alkyl Z 'in the compound of formula (IV) is especially 1-phenethyl and benzyl. The compound of formula (IV) is in a tautomeric equilibrium state (in the form of lactam / imide), and the form of lactam (formula (IV)) should be the main form. Formula (IV) is used to represent two possible forms of equilibrium. The form of internal imine has the structure of formula (IVa),

Free radicals in formula (IVa) are as defined for compounds of formula (IV). The invention also relates to novel compounds of formulae (IV) and (IVa). This method specifically uses a strong chemical dehydrating agent as the dehydrating agent, especially phosphorus pentoxide (P4001 ()). Suitable as the third amine is especially composed of three independent alkyl groups, especially lower alkyl groups (such as methyl or ethyl) and cycloalkyl groups having 3 to 7 carbon atoms, especially cyclohexyl Selected free radically substituted ammonia in a group, such as N, N-dimethyl-N-cyclohexylamine, N-ethyl-N, N-diisopropylamine or triethylamine, or pyridine, N-methylmorpholine Or 4-dimethylamine pyridine. The reaction between pyrrolimidinone of formula (IV) and the amine of formula (III) occurs at high temperature, for example, at 200 to 250 ° C. Method c) This paper size applies the Chinese national standard (CNS) Λ4 + current grid (210X297g t) installed -----. ~~ Order--1 —--- (Please read the precautions on the back before filling this page ) -31-472057 Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs A7 B7____ V. Description of the invention () The reaction is based on the exclusion of water in a suitable inert solvent (such as a suitable ether, like cyclic ether, especially like Tetrahydrofuran), at elevated temperatures, preferably under reflux. Method d)

The reaction is carried out with the exclusion of water in a suitable emotional solvent (such as a suitable halogenated hydrocarbon, especially like dichloromethane) at a temperature of about -20 ° C to + 50 ° C, preferably It is carried out under ice cooling or at room temperature. Method e) The hydrogenation reaction is carried out under high pressure or preferably at atmospheric pressure in the presence of a suitable hydrogenation catalyst (especially like nickel), in an inert solvent or solvent mixture (particularly like a suitable ring A mixture of an ether and a suitable lower alkanol, such as a mixture of tetrahydrofuran and methanol, is preferably carried out at a temperature of about 0 ° C to + 50 ° C, preferably at room temperature. Starting materials: The starting materials of formula (II) are novel, and the invention also relates to such starting materials. It can be prepared using methods similar to those described in German Patent No. 2818676 (published November 8, 1979) and German Patent No. 3036390 (published May 13, 19S2). The starting material of the formula (II) (where X is chlorine) is, for example, a compound similar to the formula (II) (where X is a hydroxyl group) is used as the starting material. The moisture content and the reflux temperature are excluded. It was obtained by reaction with phosphorus oxychloride (phosphonium chloride, P (= 0) C13). If necessary, if the starting material of formula (II) (where X is chlorine) is obtained, it can be further reacted with an amine of formula (III) in the same container, that is, a single pot reaction. For this purpose, once the paper is inversely sized with phosphorus oxychloride, the Chinese National Standard (CNS) Λ4 specification (2 丨 OX297 male Zhao) ---------, _ 装 ----- Γ1Τ- --------- Φ (Please read the precautions on the back before filling this page) -32- 472057 A7 B7 V. Description of the invention () It should be complete. The reaction mixture of the reaction is evaporated to dryness. A suitable solvent (like n-butanol) is prepared as a suspension 'and further reacted with an amine of formula (πm). A compound similar to formula (II) (where X is a hydroxyl group) is' for example, using a compound of formula (V) as a starting material, (V) (the symbol in formula (V). Is as defined above), as appropriate When in the presence of an inert solvent (such as dimethylformamide), at high temperature, for example at a temperature of 80 ° C to the boiling point, with formic acid (which is preferably used in excess, such as 10:30 molar excess, relative to Compound of formula (V)). Alternatively, a compound similar to formula (II) (where X is a hydroxyl group and the rest of the symbols are as defined above) is, for example, a compound of formula (VI) is used as a starting material,

(VI) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling this page) (R4 in formula (VI) is a lower alkyl group (especially ethyl) and the rest of the symbols are as above Defined), obtained by reacting a large excess of formamidine with a mixture of anhydrous dimethylformamide and formic acid. The reaction is carried out at a high temperature, for example, 100 ° C to 150 ° C, and preferably under a protective gas. The invention also relates to novel starting materials of formulae (V) and (VI). This paper size applies Chinese National Standard (CNS) Λ4 specification (2 丨 0X297). 33-472057 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention () Formula (V) used as intermediate 1- (Z ')-2-amine-3-cyano-pyrrole can be prepared in a high yield by a method known per se and published [see, for example, Roth, HJ, and Eger, K., Arch. Pharmaz 308, 179 (1975)]. For this purpose, for example, a compound of formula (VII) (νπ) is first reacted with a formula of z'-nh22 to form a compound of formula (νιπ) ζ '\ ΝΗ

It is then converted with the malononitrile of formula CH2 (CN) 2 to the desired intermediate of formula (V). In detail, the reaction with the amine z'-NH22 is under conventional condensation conditions, such as in the presence of a catalytic amount of a strong acid (such as hydrochloric acid or p-toluenesulfonic acid), at high temperature (preferably at the boiling point), It is carried out in a suitable solvent (such as benzene or toluene) under the exclusion of water to form each (X-amino ketone of the formula (νίπ). It is not isolated but immediately heated and further removed by water, if necessary, Compounds of formula (V) are obtained by condensing with malononitrile by adding a small amount of base (like hexahydropyridine). Compounds of formula (VI) (wherein R2 is N-section-pyridine-2- And the other symbols are as defined above, for example, a compound of formula (VI) (wherein hydrogen is private and the remaining symbols are as defined above) in a suitable solvent (such as a dentified hydrocarbon, especially like dichloromethane) ), Obtained by reaction with bromide N-benz-2-bromo-prodox. The reaction is best under a protective gas, in a dark and anhydrous state, at room temperature or high temperature (for example, 20 ° C to 80 ° C.), and the national paper standard (CNS) Λ4 specification (2! 0X297) while the paper size is 2,6- (Please read the notes on the back before filling out this page) Order -34- 472057

〇 X

1¾ Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs Λ7 B7 V. Description of the invention () Dimethyl-B-pyridine (2,6-dimethylpyridine) is carried out. The remaining compounds of formula (VI) are, for example, 2-methyl vein-lower alkyl acetate (IX) of formula (IX) (R4 in formula (IX) is as defined above) and 2-Xl- of formula (X) R2-ethyl-1-one derivative is obtained by reaction (X) (the symbol in formula (X) is as defined above). The leaving group X is preferably bromine. Before starting the reaction, using an equivalent amount of a base (especially like sodium ethoxide) under ice cooling, the 2-formamidine-lower alkyl acetate of the formula (IX) is added from its acid addition salt (especially its hydrogen chloride) Compound). The reaction is carried out in a suitable solvent (especially a lower alkanol, preferably ethanol), at a preferred temperature of 0 ° C to 50 ° C, especially at room temperature. General process conditions: The salt-forming free compound of formula (I) obtained according to this method can be converted into its salt by methods known per se, such as treatment with an acid or a suitable derivative thereof, such as adding a suitable acid to a solvent Compounds of formula (I) in a suitable solvent (e.g. ether, like cyclic ether, in particular di Ofane or more particularly tetrahydrofuran). The mixture of isomers obtained in accordance with the present invention can be separated into individual isomers by methods known per se, and the racemates can be formed, for example, by using a method and separation of salts with optically pure salt-forming reagents, and the non-mirror isomers obtained as such. The structure mixture is separated, for example, by fractional crystallization. This paper size applies to Chinese National Standard (CNS) Λ4 specification (210X 297 mm) (Please read the precautions on the back before filling this page)

-35- 472057 A7 B7, Consumer Cooperative of Employees of the Central Standards Bureau of the Ministry of Economic Affairs of the People's Republic of China 5. Description of the Invention () The above reactions can be performed under essentially known reaction conditions. Solvents or diluents (which are the best) It is inert to the reagents used and it is a solvent), it is not necessary to use or use a catalyst, a condensing agent (such as phosphorus pentoxide) or a neutralizing agent (such as a base, especially a nitrogen base, such as triethylamine hydrochloride) Depending on the nature of the reaction and / or the reactant, it can be at low temperature, normal temperature or high temperature, for example, about -80 ° C to about 200 ° C, more preferably about -20 ° C to about 150 ° C. It is carried out within a temperature range (for example, at the boiling point of the solvent used), under atmospheric pressure or in a closed container, and under appropriate pressure and / or under an inert gas pressure (for example, under a nitrogen pressure). The specific reaction conditions specified in each case are preferences. Solvents and diluents are, for example, water, alcohols, such as lower alkyl hydroxides (like methanol, ethanol, propanol or especially butanol), glycols (like ethylene glycol), triols (like glycerol), or Aromatic alcohols (like phenol), amidines, such as carboxamide (like dimethylformamide, dimethylacetamide, or 1,3-dimethyl-3,4,5,6 · tetrahydro-2 (1H ) -Pyrimidinone (DMPU)), carboxylic acids, especially formic acid or acetic acid, ammonium amines (like hexamethylphosphonium trioxamine), ethers, such as cyclic ethers (like tetrahydrofuran or dioxane) or acyclic ethers (Like ether or ethylene glycol dimethyl ether), halogenated hydrocarbons like halogen-lower alkanes (such as dichloromethane or chloroform), ketones (like acetone), nitriles (like ethyl salt), acid anhydrides (like acetic anhydride), esters (Like ethyl acetate), dialkylene bases (like dimethyl sulfoxide), nitrogen-containing heterocyclic compounds (like pyridine), hydrocarbons such as lower alkanes (like pentane) or aromatic compounds (like benzene, toluene or dioxane) Toluene), or a mixture of these solvents, a solvent suitable for the above reaction can be selected in each case. This paper size is applicable to China National Standards (CNS) Λ4 specifications (2 丨 〇 > < 297). Packing -------- ^ ~ Order-«----- (Please read the note on the back first Please fill in this page for further information) -36- 472057 Printed by A7 B7, Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention () The subsequent treatment of the compound of formula 或其 or its salt obtained using conventional methods, such as solvent decomposition of excess reagents , Recrystallization, chromatography (e.g., partition chromatography, ion chromatography, or gel chromatography), partitioning between inorganic and organic solvents, one or more extractions, especially when acidifying or increasing alkalinity or salt After content, drying, absorbing, filtering, rinsing, dissolving, evaporating and concentrating (if necessary in the air or under high air) via water-absorbent salt, distillation, crystallization (for example, crystallization of compounds obtained as oil or from mother liquor) Crystallization, which can also be seeded with final product crystals) or a combination of two or more of the subsequent processing steps mentioned (which can also be used repeatedly), etc. The starting materials and intermediates can be used in pure form (such as in the just mentioned After subsequent processing It can be used in partially purified form, or it can be used, for example, directly as a crude product. In view of the close relationship between the free form compound of formula (I) and its salt form, any of the free compounds mentioned above and below and The salts, of course, also include their equivalent salts and free compounds, respectively, where appropriate and convenient, provided the compounds contain a salt group. Compounds (including their salts) can also be obtained in the form of hydrates, or their crystals can contain, for example, for crystallization Solvents. In the method of the present invention, the starting materials used are those which are described in the beginning as forming novel compounds of formula (I) of particular value. The present invention also relates to those forms of the method, in which at any stage The obtained intermediate product is used as the starting material and the remaining steps are performed, or the starting material is formed under reaction conditions or used in the form of its derivative (such as its salt). 4 Specifications (210 '乂 297 Public Incense) --------- | ^ Crack ----- rtr ------- ^ w. (Please read the precautions on the back before filling in this page ) -37- 472057 A7 Employees of the Central Bureau of Standards of the Ministry of Economic Affairs of the People's Republic of China F. Cooperative cooperatives' printing bags V. Description of the invention () The present invention is particularly related to a ratio of the formula (Ia) 幷 [2,3-d] Range) or a salt thereof '(la), wherein η is 1 to 3, and R is hydrogen, halogen, lower alkyl, hydroxy, lower alkoxy, lower alkoxy, carboxy, lower Alkoxycarbonyl, carbamoyl, N-lower amine-carbamyl, N, N-di-lower amine-carbamyl, cyano, amine, lower carbamoylamine, lower alkylamine, Ν , N-di-lower alkylamino or trifluoromethyl 'When there are several free radicals R in the molecule, these radicals may be the same or different, a) R, and R2 are independent, and are phenyl, amine , Lower alkylamino, lower alkylamino, N, N-di-lower alkylamino, hydroxyl, lower alkyloxy, carboxyl, lower alkoxycarbonyl, carbamoyl, N-lower alkyl-amine formamidine Phenyl, N, N-di-lower amine-carbamoyl, cyano or nitro substituted phenyl is hydrogen, unsubstituted or pyridyl substituted with halo or lower alkyl, is N-section- Fluoren-2-yl, naphthyl, cyanide Group, carboxyl group, lower alkoxycarbonyl group, carbamoyl group, N-lower alkane-carbamyl group, N, N-di-lower amine-carbamyl group, methyl group, lower alkynyl group, lower alkenyl group, Lower alkenyloxy, or halogen, amine, lower alkylamino, hexahydropyridyl, dilower alkylamino, hydroxyl, lower alkoxy, cyano, carboxyl, lower alkoxycarbonyl, carbamoyl , N-lower compound-carbamoyl, N, N-di-lower alkyl-carbamoyl, mercapto or a radical of the formula RrSiOV- (wherein the lower alkyl group and m is 0, 1 or 2) Lower alkyl, or

(Please read the precautions on the back before filling this page): Install it This paper size applies to the Chinese National Standard (CNS) Λ4 specification (210X297 mm) -38- Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 472057 A7 B7___ 5 2. Description of the invention (b) one of the radicals & and & is an unsubstituted lower alkyl group or an unsubstituted phenyl group, and the other of the radicals R and R2 has the above a) Specify one meaning (other than hydrogen), or ^ and ^ together are amine, lower alkylamino, lower alkylamino, N, N-di-lower alkylamino, nitro, halogen, hydroxyl, Lower alkoxy, lower alkoxy, carboxyl, lower alkoxycarbonyl, carbamoyl, N-lower alkyl-carbamoyl, N, N-di-lower alkyl-carbamoyl or cyano substituted 〇C1 (rl, 4-alkylene dienyl, or Πα-1,4 · alkylene dienyl having up to 9 carbon atoms, the method includes a) a pyrrolidine of formula (II) [ 2,3-d] pyrimidine derivatives

(X in formula (II) is an appropriate leaving group, Z is hydrogen or 1-aryl_lower alkyl group and the rest of the substituents are as defined above for the compound of formula (la). Any free radical is protected by an easily removable protecting group) with an amine derivative of the formula (Ilia), (R) n (Ilia) (R and η in the formula (Ilia) are the same as those of the compound of the formula (la) above Definition, if necessary, any free functional group present in the radical R is protected by a protective group that can be easily removed), and any protective group present and (where present) 1-aryl-lower alkyl radical Z, or this paper Standards are applicable to Chinese National Standards (CNS) Λ4 specifications (2 丨 0 '乂 297mm) --------- installation -------- order ------- (Please read the back first Please note this page and fill in this page again) -39- 472057 A7 B7 V. Description of the invention () b) In the presence of a dehydrating agent and a tertiary amine, pyrrolidine [2,3-d] of formula (IV) is chewed steeply- 4-keto derivatives

Printed by the Consumers 'Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs (wherein Z' is a 1-aryl-lower alkyl group in formula (IV), and &amp; as defined in the above formula (⑻ compound, if necessary, radical &amp; Any free functional group present is protected by an easily removable protective group) and reacted with more than one aniline of formula (II), and any protective group present is removed, or c) a compound of formula (la) (wherein Z When the amine methyl group and other substituents are as defined for the compound of formula (la) above, a compound corresponding to formula (la) (wherein the heart is hydrogen and the remaining substituents are as for the compound of formula (la) above) The definition, if necessary, any free functional group present in the free radicals and protected by protective groups that can be easily removed) reacts with tritiated HN-dimethyl-methyleneimmonium, and remove any protective groups present, or d) when preparing a compound of formula (la) (wherein at least one of the radicals R, & and &amp; is a phenyl group substituted by a hydroxyl group, and the remaining substituents are the same as those defined by the compound of the formula (la &gt;), a Compounds of formula (la) (wherein at least one of the radicals R, &amp; and ^ are Methoxy substituted phenyl, and the rest of the substituents are as defined for the compound of formula (la) above, if necessary, the free radical R, the protector of any free functional group present in the heart can be easily removed) and three Boron bromide reacts and removes any protective groups present, or e) prepare a compound of formula (la) (wherein at least one of the free radicals R, R and R is a phenyl group substituted with an amine group, and the remaining substituents are as above formula Definition of (Ia) ^ compound This paper size applies the Chinese National Standard (CNS) A4 specification (210 × 297 mm) <Please read the notes on the back _ 4 items before filling and packing —: write this page) • order, φ. -40- 472057 5. In the description of the invention (1), a compound corresponding to formula (la) (at least one of the radicals R, &amp; and &amp; is a phenyl group substituted by a nitro group, and the rest The substituents are as defined for the compound of formula (la) above. When necessary, any free functional groups present in the free radicals R, R and R2 are protected by a protective group that can be easily removed), and any protective groups present are removed, And after implementing one of the methods a) to e) When a salt is prepared, 'the free compound of the formula (la) formed is converted into a salt, or when a free compound is necessary to be prepared, the salt of the compound of the formula (VII) is converted into a free compound. The present invention also relates to pyrrole of the formula (Ua) [2,3-d] pyrimidine derivatives (please read the precautions on the back before filling this page) -pack.

In the formula (11a), χ is a hydroxyl group or a leaving group, Z is hydrogen or a 1-aryl-lower alkyl group, and &amp;) &amp; _Methoxy, benzyloxy methoxy, lower alkoxy-methoxy, phenyl, amine, lower alkylamino, lower alkylamino, N, N_di-lower alkylamino, hydroxyl 、 Printed base, finished base, lower alkoxycarbonyl, carbamoyl, N-lower alkane-aminoformamyl, N'N 'second-lower institute-amine form Amidino, cyano, or nitro-substituted phenyl is pyridyl which is unsubstituted by hydrogen or substituted by halo or lower alkyl, and is N-pyridine, 4-methyl, fluorenyl, fluorenyl, cyano, carboxyl, Lower alkoxycarbonyl, carbamoyl, &amp; lower fluorenyl-carbamyl, Ν, Ν · di-lower alkane-carbamyl, benzyl-carbamyl, fcfe ether group, lower alkynyl, Lower alkenyl, lower alkenyloxy, or amine, lower alkylamino, hexahydropyridyl, di-lower alkylamine. This paper is fine &quot; for use--41-472057 Employees of the Central Standards Bureau of the Ministry of Economic Affairs Printed by a cooperative A7 B7 V. Description of the invention () group, aniline group (which is unsubstituted or substituted by halogen, lower alkyl group, hydroxyl group, lower alkoxy group, lower alkoxy group, carboxyl group, lower alkoxycarbonyl group, Carbamate, N-lower alkyl-carbamate, N, N-di-lower alkyl-carbamate, cyano, amine, lower carbamate, lower alkylamine, N, N-la Lower alkylamino or trifluoromethyl substituted), hydroxyl, lower alkoxy, cyano, carboxyl, lower alkoxycarbonyl, carbamoyl, N_lower house · aminomethyl, N, N-secondary -Aminomethyl, fluorenyl, or radicals of the formula R3-S (0) m- (wherein R3 is lower alkyl and m is 0, 1 or 2) substituted lower alkyl, or b) free radical &amp; And one of &amp; is an unsubstituted lower alkyl group or an unsubstituted phenyl group, and the other of the radicals and &amp; has the meaning specified in a) above (apart from hydrogen) , Or £ 〇111 and 112—unsubstituted or substituted by amine, lower alkylamino, lower alkylamino, N, N-di-lower alkylamino, nitro, halide, hydroxyl, lower alkyl Oxygen, lower alkane Oxo, carboxyl, lower alkoxycarbonyl, carbamoyl, N-lower alkyl-carbamoyl, N, N-di-lower alkyl-carbamoyl or cyano substituted C4-C1 (rl, 4_ Alkylenedienyl, or Bamma-1,4-alkylenedienyl having up to 9 carbon atoms, and related 4-keto derivatives (which are compounds of formula (Ila) (where X ' Tautomers) and salts of these compounds. The present invention relates particularly to pyrrole [2,3-d] pyrimidine derivatives of formula (Ua), where X 'is a hydroxyl group or a leaving group, Z Is hydrogen or 1-aryl-lower alkyl, and 3) & and 112 are each independently phenyl, amine, lower alkylamino, lower alkylamino, N, N-di-lower alkylamino, Hydroxyl, lower alkoxyl, carboxyl, lower alkoxycarbonyl, carbamoyl, N-lower amine-carbamyl, N, N- two paper sizes are applicable to Chinese National Standard (CNS) A4 specifications (2 丨〇: &lt; 297 Gongchu) la— ml mV · λ1— · ΚΒΙ— tua— ^^ ΒΒ— nn nn m &gt; —— J. Nn · 11 ml i km (Please read the precautions on the back before filling this page ) -42- 472057 A7 B7 V. Description of the invention () Lower alkanes- Formyl, cyano, or nitro-substituted phenyl is hydrogen, unsubstituted or pyridyl substituted with halo or lower alkyl, and is N · n-Ubyl, naphthyl, cyano, Carboxyl, lower alkoxycarbonyl, carbamoyl, N-lower alkane-carbamyl, N, N-di-lower amine • carbamoyl, formamyl, lower alkanoyl, lower alkenyl, lower alkenyl Oxy, or halogen, amine, lower alkylamino, hexahydropyridyl, di-lower alkylamino, hydroxyl, lower alkoxy 'cyano, carboxyl, lower alkoxycarbonyl, carbamate, N -Lower grades-carbamoyl, N, N-di-lower grades-carbamoyl, fluorenyl or radicals of the formula RrSiOl- (where R3 is lower alkyl and m is 0, 1 or 2) substituted lower Alkyl, or b) one of the radical ratios and & is an unsubstituted lower alkyl or unsubstituted phenyl, and the other of the radicals &amp; and 112 has the one specified in a) above Meaning (other than hydrogen), or phantoms 111 and 112 are unsubstituted or amine, lower alkylamino, lower alkylamino, N, N-di-lower alkylamino, nitro, Halogen, hydroxyl Lower alkoxy, lower alkoxy, carboxyl, lower alkoxycarbonyl, carbamoyl, lower amine-carbamyl, N, N-lower amine · carbamyl or cyano substituted C4- C1 (rl, 4-alkylene dienyl, or 11A-1,4 &gt; alkylene dienyl having up to 9 carbon atoms, and related 4-keto derivatives (which are of formula (na) Tautomers of compounds (wherein X is a hydroxyl group) and salts of these compounds. Compounds of formula (Ila) and 4-keto derivatives (which are tautomers of compounds of formula (na) (where X 'is a hydroxyl group)) can be used as the formulae (Π), (IV), and ( IVa) starting materials and are prepared using methods similar to those used to prepare those starting materials. The present invention also relates to pyrrole derivatives of formula (XI) and salts of these compounds. The size of this paper is applicable to the Chinese National Standard (CNS) Λ4 specification (210X297 mm) (This page) -Ding, -1 ° Printed by the Consumers' Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs -43-472057

A7 B7 5. Description of the invention () (XI), Z in the formula (XI) is hydrogen or 1-aryl-lower alkyl, 3) Gen and 112 are independent of each other, and are amine formamidine · methoxy, carboxy- Methoxy, benzyloxy-methoxy, lower alkoxycarbonyl-methoxy, phenyl, amine, lower alkylamino, lower alkylamino, N, N-di-lower alkylamino, hydroxyl, Lower alkoxyl, carboxyl, lower alkoxycarbonyl, carbamate, N-lower alkane-carbamoyl, N, N-di-lower alkane-carbamoyl, cyano or nitro-substituted phenyl , Is hydrogen, unsubstituted or pyridyl substituted by halo or lower alkyl, is N-〒 · pyridin-2-yl, naphthyl, cyano, carboxyl, lower alkoxycarbonyl, carbamate , NR-lower amine-carbamyl, Ν, Ν-di-lower alkane-carbamyl, NH-benzyl-carbamyl, formamyl, lower carbamyl, lower alkenyl, lower alkenyloxy Or by halogen, amine, lower alkylamino, hexahydropyridyl, di-lower alkylamino, aniline (which is unsubstituted or substituted by halogen, lower alkyl, hydroxyl, lower alkyl in the phenyl moiety Oxy, lower alkoxy, carboxyl, lower alkoxy Carbonyl, carbamoyl, N-lower alkyl-carbamoyl, N, N-di-lower alkyl-carbamoyl, cyano, amine, lower alkylamino, lower alkylamino, Ν, Ν -Di-lower alkylamino or trifluoromethyl substituted), hydroxyl, lower alkoxy, cyano, carboxy, lower alkoxycarbonyl, carbamate, N-lower house-carbamate, N, N- Second lower grade-Aminomethyl, fluorenyl or RrSP) ™-free radical (where R3 is lower alkyl and m is 0, 1 or 2) substituted lower alkyl, or the Chinese standard is applicable to this paper (CNS) Λ4 specification (210X297) 漦 tt nn nn ji 1 ^ 1 nn nn In nnj · 11 · i (Please read the precautions on the back before filling this page) Printed by the Staff Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs -44 -472057

Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs I A7 B7__V. Description of the Invention () b) One of the radicals &amp; 112 is an unsubstituted lower alkyl group or an unsubstituted phenyl group, and the radical private And the other of 112 has one of the meanings specified in a) above (other than gas), or is magical! 11 together with &amp; is unsubstituted or amine, lower alkylamine, lower alkylamine Group, N, N-di-lower alkylamino, nitro, halogen, hydroxy, lower alkoxy, lower alkoxy, carboxy, lower alkoxycarbonyl, carbamoyl, N-lower alkyl-amine formamidine , N, N-di-lower-Cyclomethylamino or cyano-substituted C4-C10-l, 4-alkanedienyl, or 11A-1,4- with up to 9 carbon atoms Butanedienyl, d) when q is 1, z and 112 are each independently unsubstituted lower alkyl or unsubstituted phenyl, or have the meaning specified in a) above, and r5 is Cyano or lower alkoxycarbonyl. The present invention particularly relates to pyrrole derivatives of the formula (XI) and salts of these compounds, in which Z is hydrogen or 1-aryl-lower alkyl, 3) each of 112 and 112 is independently phenyl, amine, or lower alkyl Fluorenylamino, lower alkylamino, N, N-di-lower alkylamino, hydroxyl, lower alkoxy, carboxyl, lower alkoxycarbonyl, carbamoyl, N_lower compound-carbamoyl, Ν , N-di-lower amido, cyano, or nitro-substituted phenyl is hydrogen, unsubstituted or pyridyl substituted with halo or lower alkyl, is N-segment-fluorene-2 -Yl, decyl, cyano, carboxyl, lower alkoxycarbonyl, carbamoyl, N-lower alkyl-carbamoyl, N, N-di-lower fluorenyl-carbamoyl, formamyl, lower alkyl Fluorenyl, lower alkenyl, lower alkenyloxy, or halogen, amine, lower alkylamino, hexahydropyridyl, dilower alkylamino, hydroxyl, lower alkoxy, cyano, ^ n- mm ·· m · ϋ n — ^^ 1 In I In I nn ** One h tft ^ — 1m Φ. (Please read the precautions on the back before filling this page) This paper size applies to China National Standard (CNS) A4 specifications (2 丨 0X297 mm ) -45- 472057

Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs. 5. Description of the invention () Carboxyl, lower alkoxycarbonyl, carbamoyl, N-lower institute-aminoformamyl, N, N-second lower institute-amineformamyl , Fluorenyl or a radical of the formula RrS (0) „r (where R3 is a lower alkyl group and m is 0, 1 or 2) a substituted lower alkyl group, or one of b) free radicals &amp; 112 is unsubstituted A substituted lower alkyl group or an unsubstituted phenyl group, and the other of the radicals &amp; and ^ has one of the meanings specified in a) above (other than hydrogen), or together with &amp; Unsubstituted or substituted by amine, lower alkylamino, lower alkylamino, N, N-di-lower alkylamino, nitro, halogen, hydroxyl, lower alkoxy, lower alkoxy, carboxyl, Lower alkoxycarbonyl, carbamoyl, N-lower amine-carbamyl, N, N-di-lower amine-carbamyl, or cyano-substituted C4-C10-1,4-butanedienyl , Or a γ-1,4-alkylene dienyl group having up to 9 carbon atoms, and R5 is a cyano group or a lower alkoxycarbonyl group. A pyrrole derivative of the formula (XI) can be used as the above formula (V ) And (VI), and It is prepared by a method similar to the preparation of those starting materials. The present invention also relates to the intermediates of formula (Ila) and (XI), wherein the definition of the substituents is to obtain the compound of formula (I) in the first patent application scope as Principles. Pharmaceutical compositions, their preparation and uses of the compounds of formula (Π) and compositions containing these compounds as active ingredients The present invention also relates to pharmaceutical compositions that contain a compound of formula (I) as an active ingredient and can be particularly For the treatment of the diseases mentioned at the beginning. Particularly preferred pharmaceutical compositions are the enteral for warm-blooded animals (including humans), such as nasal, buccal, rectal or especially oral compositions, and parenteral compositions Materials, such as intravenous, intramuscular, or subcutaneous injection. The composition is contained separately (please read the precautions on the back before filling this page): Binding and ordering Φ This paper size applies to Chinese national standards (CNS &gt; Λ4 specifications) (2 丨 〇 &gt; &lt; 297 Public Office) -46- 472057 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention () The effective ingredients may preferably be combined with a pharmaceutically acceptable carrier. The dosage of the active ingredient depends on the disease and species to be treated, its age, weight and individual status, pharmacokinetic data, the disease to be treated and the mode of administration. The invention also relates to the use of the pharmaceutical composition in the method of treating human or animal body, its preparation method (especially in the form of a composition for treating tumors) and a method for treating tumor diseases (especially those mentioned above) . Preferred is a medicinal composition suitable for administering a warm-blooded animal (especially a human) suffering from a disease (such as psoriasis or tumor) that responds to protein kinase inhibition, which contains a compound of formula (I) that is effective in inhibiting protein kinase Or a salt thereof (when a salt-forming group is present), together with at least one pharmaceutically acceptable carrier. The pharmaceutical composition contains about 1% to about 95% active ingredients. Single-dose dosage forms preferably contain about 20% to about 90% active ingredients. Non-single-dose dosage forms preferably contain about 5% to about 20% active ingredients. Single-dose forms are, for example, sugar-coated tablets, lozenges, ampoules, potions, suppositories or capsules. Other dosage forms are, for example, ointments, creams, pastes, foam tinctures, tinctures, lipsticks, drops, sprays, suspensions, and the like. An example is a capsule containing from about 0.05 grams to about 1.0 grams of active ingredient. The pharmaceutical composition of the present invention is prepared by a method known per se, such as a conventional mixing, granulating, sugar-making, dissolving or freeze-drying method. Preference is given to using solutions and suspensions or dispersions of the active ingredient, in particular isotonic aqueous solutions, dispersions or suspensions, which, for example, are frozen in the presence of the active ingredient alone or in the same carrier (such as mannitol) Dry paper size is applicable to China National Standard (CNS) A4 specification (2 丨 〇 &gt; &lt; 297 public 牦） m HBH tm It ϋ ·-1 Lei nn mu mi n ^ — m 、 一 If -JI— it m · (Please read the precautions on the back and fill in this page first) -47- 472057 Economy Printed by the Consumer Standards Cooperative of the Ministry of Standards, Ministry of Standards, A7 and B7 V. Description of Invention () The composition can be adjusted before use. The pharmaceutical composition may be sterilized and / or may contain adjuvants, such as preservatives, stabilizers, moisturizers and / or emulsifiers, solubilizers, salts and / or buffering agents that regulate osmotic pressure, and utilize the essence It is prepared by a method known above, for example, using a conventional dissolution and freeze-drying method. The above solutions or suspensions may contain viscosifying substances such as sodium carboxymethylcellulose, carboxymethyl cellulose, polydextrose, polyvinylpyrrolidone or gelatin. Oil suspensions contain vegetable oils for injection, synthetic or semi-synthetic oils as an oil component. A liquid fatty acid ester is particularly proposed here, which contains a long-chain fatty acid having 8 to 22, especially 12 to 22 carbon atoms, as an acid component, such as lauric acid, tridecanoic acid, myristic acid, fifteen Acid, palmitic acid, pearlic acid, stearic acid, arachidic acid, rosic acid, or equivalent unsaturated acids, such as oleic acid, oleic acid, erucic acid, brassic acid, or linoleic acid. An oxidant, such as vitamin E, β-carotene or 3,5-di-tert-butyl ice, is passed through toluene. The alcohol component of these fatty acid esters has up to 6 carbon atoms and is a mono- or poly-hydroalcohol, such as a mono-, di-, or tri-hydroalcohol, such as methanol, ethanol, propanol, butanol, or pentyl alcohol. Alcohol or its isomers, especially ethylene glycol or glycerol. The following examples of fatty acid esters are therefore proposed: ethyl oleate, isopropyl myristate, isopropyl palmitate, &quot; Labrafil M 2375 &quot; (polyoxyethylene glycerol trioleate, Gattefoss6, Paris), ^ Miglyolpl '(saturated fatty acid diglycerol with a bond length of C8 to C12, Chemische Werke Witten / Ruhr, Germany), especially vegetable oils, like cotton Seed oil, almond oil, olive oil, castor oil, sesame oil, soybean oil, and more particularly peanut oil. This paper size applies to the Chinese National Standard (CNS) Λ4 specification (2 丨 〇2 () 7 male male) I-nnnnn- (Please read the notes on the back before filling this page) • Packing--Order -48- 472057 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention () The injection composition is used under sterile conditions. It is prepared by the method; also in the same aseptic state, the composition is filled into an ampoule or a medicine bottle and sealed. The oral pharmaceutical composition can be obtained, for example, by combining an active ingredient with one or two solid carriers. Formed mixture Granules, and, if necessary or necessary, additional adjuvants are added to process the mixture or granules into lozenges or dragee cores. Suitable carriers are especially fillers, such as sugars (such as lactose, sucrose, mannitol or glucositol) , Cellulose products and / or calcium phosphate (such as tricalcium phosphate or dibasic calcium phosphate), and binding agents such as starch (such as corn, wheat, rice, or potato starch), methyl cellulose, hydroxypropyl methyl cellulose , Sodium carboxymethylcellulose and / or polyvinylpyrrolidone, and / or, if necessary, dispersants, such as the above-mentioned starches, and carboxymethyl starch, cross-linked polyvinylpyrrolidone, alginic acid or a salt thereof (Like sodium alginate). Additional adjuvants are in particular flow regulators and lubricants, such as silicic acid, talc, stearic acid or its salts (like magnesium stearate or calcium stearate) and / or polyethylene glycol Or a derivative thereof. The sugar-coated tablet core may be coated with a suitable, selectively enteric coating, especially using a concentrated sugar solution, which may contain gum arabic, talc, polyvinylpyrrolidone, polyethylene glycol, and / or titanium dioxide, Or dissolved in a suitable organic solvent or Coating solution in agent mixture, or, for the preparation of enteric coatings, use a solution of appropriate cellulose products, such as ethyl cellulose phthalate or hydroxypropyl methyl cellulose phthalate. Dyes or pigments can be added in lozenges Or sugar-coated tablets, for example, for identification purposes, or to indicate the effective ingredients of different doses. This paper size applies the Chinese National Standard (CNS) Λ4 specification (21〇X2 [) 7 meters) I -------- 0 ^ ----- ^ 丨 -Order one ^ ----, 9. (Please read the notes on the back before filling this page) -49- 472057 A7 B7 Printed by the Central Standard of the Ministry of Economics 扃 Printed by the Staff Consumer Cooperative 2. Description of the invention () Oral pharmaceutical composition also includes dried filling capsules made of gelatin, and soft sealed capsules made of gelatin and plasticizers (such as glycerol or glucosyl alcohol). Dry capsules can contain granular active ingredients, such as blended tinctures (like corn starch), binders and / or lubricants (like talc or magnesium stearate), and optionally stabilizers. In soft capsules, the active ingredient should be dissolved or suspended in a suitable liquid adjuvant (such as fatty oil, paraffin oil or liquid polyethylene glycol or glycol or glycerol fatty acid esters). Detergents and detergents (such as polyoxyethylene gluconate fatty acid type detergents). Other oral dosage forms are, for example, syrups prepared by conventional methods, containing, for example, a suspended form at about 5% to 20%, more preferably at a concentration of about 10% or a similar concentration providing a suitable single dose (for example, in 5 or 10 ml). Also suitable formulations are, for example, powder or liquid concentrates for the preparation of mixtures (for example in emulsions). This concentrate can also be packaged in single doses. Suitable pharmaceutical compositions for rectal use are, for example, suppositories consisting of a combination of an active ingredient and a suppository base. Suitable suppository substrates are, for example, natural or synthetic triglycerides, paraffin hydrocarbons, polyethylene glycols or higher alkanols. For parenteral administration, in particular the use of a suitable aqueous solution of the active ingredient in a water-soluble form (such as a water-soluble salt form) or a viscosity-increasing substance (such as sodium carboxymethyl cellulose, glucose alcohol and / or polydextrose) and, When needed, water-soluble injection suspensions containing stabilizers. The active ingredients, optionally together with adjuvants, can also be in the form of lyophilisate, and can be made into a solution by adding appropriate solvents before parenteral administration. I -------- Installation-(Please read the precautions on the back before filling out this page) • Ding-55 This paper size applies Chinese National Standards (CNS) Λ4 grid (21〇 × 2ι) 7 males ) -50- 472057 A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs. 5. Description of the Invention () Solution, like, for example, a solution for parenteral administration can also be used as an infusion solution. Preferred preservatives are, for example, antioxidants (like ascorbic acid) or microbicides (like sorbic acid or benzoic acid). Ointments are oil-water type emulsions, which contain up to 70%, but more preferably 20% to 50% water or water phase. Those suitable as the lipid phase are especially hydrocarbons, such as petroleum jelly, paraffin oil or hard paraffin, which, in order to increase the water binding amount, should suitably contain an appropriate hydroxy compound, such as a fatty alcohol or an ester thereof, such as cetyl alcohol or wool wax. Alcohol, like wool wax. Emulsifiers are comparable lipophilic substances, such as sorbitan fatty acid esters (Spans), such as sorbitan oleate and / or sorbitan isostearate. Additives to the water phase are, for example, wetting agents, like polyols, such as glycerol, propylene glycol, dextrose and / or polyethylene glycol, and preservatives and fragrances. Oily ointments are anhydrous ointments, and the substrates they contain are particularly hydrocarbons, such as paraffin, petroleum jelly, or paraffin oil, and natural or partially synthetic oils and fats (such as coconut triglycerides) or more suitably hardened oils ( Such as hydrogenated peanut oil or castor oil) and glycerol fatty acid partial esters (such as glycerol mono and / or di-stearate), and, for example, fatty alcohols, emulsifiers and / or related ointment extracts to increase water absorption The emulsion is an oil-water type emulsion containing more than 50% water. Those used as oily bases are especially fatty alcohols (such as lauryl alcohol, cetyl alcohol or stearyl alcohol), and fatty acids (such as palmitic acid or stearic acid). , Liquid-to-solid waxes (such as isopropyl myristate, wool wax or beeswax) and / or hydrocarbons (such as petroleum jelly (Shijie -------- 装 ----- ^ --- Order — U ---- (Please read the notes on the back before filling out this page) This paper size is applicable to the Chinese National Standard (CNS) Λ4 specification (210X 297 issued) 472057 Printed by the Staff Consumer Cooperative of the Central Bureau of Standards, Ministry of Economic Affairs Preparation Λ7 B7 V. Description of the invention () Fat) or paraffin oil). Suitable milk Agents are surfactants with superior hydrophilic properties, like comparable nonionic emulsifiers, such as polyalcohol fatty acid esters or their ethylene oxide adducts, like polyglycerol fatty acid esters or polyoxyethylene sorbitan fatty acid esters. (Tweens), and polyoxyethylene fatty alcohol ethers or fatty acid esters, or equivalent ionic emulsifiers, like alkali metal salts of stearyl sulfate, such as sodium lauryl sulfate, cetyl sulfate sodium, or hard sulfate Sodium fatty esters, which are usually used in the presence of fatty alcohols (such as cetyl alcohol or stearyl alcohol). The additives in the aqueous phase are in particular emulsifier-reducing agents such as polyhydric alcohols, such as glycerol, dextrose, propylene glycol and / or Polyethylene glycol, as well as preservatives and fragrances. Pastes are emulsions and ointments with powder components that absorb secretions, such as metal oxides (such as titanium oxide or zinc oxide) and talc and / or aluminum oxalate. To bind any existing water or secretions. Foam tincture is administered from a pressurized container and is a liquid aerosol in the form of an aerosol_ water emulsion; halogenated hydrocarbons (like chlorofluoro-lower alkanes, steel j Such as digas ^ difluoromethane and dichlorotetrafluoroethane ) Or more suitable gas phase smoke, air, N, 0 or carbon dioxide which is not __7 is used as the propelling gas. Those used as the oil phase are especially those users in the case of the above ointments and emulsions; Tinctures and solutions usually have an aqueous-ethanolic base. Polyols (such as glycerol, glycols, and / or polyethylene glycols) are especially added to% _ as a wetting agent to reduce evaporation, and to repair fat. Substances (like low-molecular-weight | ^ fatty acid esters of ethylene glycol), that is, lipophilic substances dissolved in an aqueous mixture ^ θ as a substitute for fatty substances removed from the skin by ethanol, and, if necessary &gt; Touch, ft agent and the size of this paper are applicable to China National Standard (CNS) Λ4 specification (210X297g t) --------- 0 ^ — (Please read the precautions on the back before filling this page), One $ -52- 472〇57 KI B7 V. Description of the invention () The present invention also relates to a method for treating the above-mentioned pathological symptoms, especially those that respond to protein kinase inhibition. In terms of prevention or medical treatment, the compound of formula (1) may be used alone or in the form of a pharmaceutical composition, preferably in an amount effective against the above diseases, and administered to a warm-blooded animal (such as a human) in need of treatment. Use as a composition. In the case of a body weight of about 70 kg, a daily dose of about 0.1 g to about 5 g 'is more preferably about 0.5 g to about 2 g of a compound of the present invention. The following examples are used to illustrate the present invention, but the scope is not limited. The abbreviations and abbreviations used have the following definitions: (Gradient): High pressure liquid chromatography (HPLC) gradient: within 20 minutes, 20%-100% a) the solution in b). Solvent solution a): acetonitrile + 0.05% TFA; eluate solution b): water + 0.05% TFA. Columns of Ci8_NucleOsil® (5 micron average particle size, covalently derived from octadecane silane, Macherey & Nagel, Duren, Germany) column (25 × 4.6 millimeters using 254 dust meters) The detection of ultraviolet (UV) absorption. Retention time (tRet) is the unit. Flow rate: 1mm / min. Printed by abs. Brine DEPc DMF DMs of the Central Consumers Bureau of the Ministry of Economic Affairs (please read the precautions on the back first) Refill this page) Absolute (anhydrous) saturated solution of sodium chloride diethyl pyrocarbonate (diethyl dicarbonate) dimethylformamide 1,3-dimethyl-3,4,5,6-tetrahydro- 2 (1 India-Pyrimidinone dimethyl sulfoxide Ben's Zhang ruler ;, 4; Zhong _ house materials (c 8 4 specifications (2 丨 0X297 mm) -53- 472057 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention () EI-MS Electron Impact Ionization Mass Spectrometry FAB-MS Fast Atomic Impact Spectroscopy HPLC High Pressure Liquid Chromatography HY High Hollow Min Min mp Melting Point MS Mass Spectrometry RT Room Temperature TFA Trifluoroacetic Acid THF tetrahydrofuran TLC thin layer chromatography TLC-Rf TLC Rf 値 TPTU tetrafluoroborate 0- (1 &gt; Hydrogen_2_oxy-1-pyridine) · N, N, N ·, N'_ Abbreviations used in nuclear magnetic resonance (NMR) spectral data b broad d doublet J coupling constant m multiplet q quadruple Peak S Singlet t Triplet Note: "&quot; Hexane〃 stands for a mixture of hexane isomers alone. Butanol, w stands for n-butanol 单独. This paper size applies to Chinese National Standard (CNS) Λ4 specifications (2! 〇Χ297 公 篼) m- m I ϋϋ nn UK In— (mi nn m J. nn An tm HI In (Please read the precautions on the back before filling out this page) -54 · 472057 Staff of the Central Standards Bureau, Ministry of Economic Affairs Printed by Consumer Cooperative A7 B7 V. Description of the invention () Example 1: 4- (3-Chloro-aniline) -6- (pyridin-2-yl) -7H-pyrrole 幷 2,3-d ~ | Under an argon pressure, 40 ml of DMPU was added to 6.53 g (28.3 mmol) of 4-chloro-6- (pyridin-2-yl) -7H-pyrrolo [2,3-d] pyrimidine and 4.6 ml (42.5 mmol) ) 3-Chloro-aniline was dissolved in 90 ml of n-butanol solution φ, and the reaction mixture was stirred for 12 hours at 1 °° {:,. The dark brown suspension was cooled and filtered. Further products can be obtained from In the mother liquor, use 100 It was obtained by precipitation in ml of water. Digestion with ethanol / tetrahydrofuran yielded the title compound: melting point> 300 ° C; W-NMR (360 MHz * DMSO-de): 12.49 and 9.66 (2s, 2H), 8.63 (d, J = 5 , 1H), 8.40 and 8.25 (2s, 2H), 7.91 (m, 2H), 7.84 (d, J = 8, 1H), 7.57 (s, 1H), 7.33 (m, 2H), 7-06 (d , J = 8, 1H); HPLC: tRet (Grad2. ) = 10.1 minutes; MS: (M) + = 32. The starting material was prepared as follows: Step 1.1. Desertification of 2- (5-amine ~ 4-ethoxy-1H-B than pyr-2-yl)- The N-fluorene-B ratio was 658 mg (2.0 mmol) of N-benzyl-2-bromo-bromide (refer to J. Heterocyclic Chem. 28, 1083 (1991)) under an argon pressure. Add 20 ml of absolute dichloromethane, and add 308 mg (2.0 mmol) of 2-amine-η ratio slightly_3_ ethyl carboxylic acid [for the preparation method, see: J. Heterocyclic Chem. 23, 1555 (1986)] among them. The reaction mixture was stirred in the absence of light for 2 days. Since the reaction was incomplete, 232 µl (2 mmol) of 2,6-lutidine and another 0.20 mmol of ethyl 2-amine-pyrrole-3-carbinate were added. After stirring for another 12 hours, the reaction mixture was concentrated by evaporation and the residue was digested in isopropanol. Filtration, washing with hexane and drying gave the title compound, which, according to its 1H-NMR spectrum, still contained approximately 10% bromide N-benz-2-bromo-Π ratio ingot; ifi-NMR (300 MHz, DMSO -d ^): 11.45 (1H), 8.70 (d, J = 7, 1H), 8.38 (t, J = 7, 1H), 8.00 (d, J = 7, 1H), 7.67 (t, J-7 , 1H), 7.42 (m, 3H), 7.14 (d, J = 7, 2H), 6.85 (d, J = Chinese paper standard (CNS) Λ4 specification (210X 297 cm)) --- ------ Equipment ----- ^-ITI, ---- (Please read the notes on the back before filling this page) -55-Printed by the Staff Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 472057 A7 B7__ 5. Description of the invention () 3, 1H), 6.45 (sb, 2H), 5.91 (s, 2H), 4.13 (q, J = 7, 2H), 1.19 (t, J = 7, 3H); FAB-MS : (M + H) + = 322 ° Step 1.2: 6- (pyridin-2-yl) -7-pyrrolidine 2,3- (1) Pyrimidin-4-ol under a protective gas, 27.07 Gram 2- (5-amine-4 · ethoxyfluorenyl-1I-pyrrole-2-yl) -N-fluorenyl-D ratio solution of 195 ml formamidine and 97.6 ml DMF (dried through 4A molecular sieve) And 48.8 ml of formic acid were heated at 150 ° C for 16 hours. When the dark brown reaction mixture was When cooling in the bath, the title compound crystallized, which was filtered off and washed with isopropanol and ether; h-NMRGOOMHz, DMSO-de): 12.5 R 11.9 (2s, 2H), 8.60 (d, J = 7, 1H), 8.05-7.8 (m, 3H), 7.28 (dd, J, = 7, J2 = 9, 1H), 7.20 (s, 1H); FAB-MS: (M + H) + = 213. Step 1.3: 4-Chloro-6- (pyridin-2-yl) -7H-pyrrole, 2,3-d, pyrimidine. With the exclusion of water, 7.05 g (33.2 mmol) of 6- (B is steeper than- 2-Hydroxy) -7H-pyrrolo [2,3-d] pyrimidine · 4-ol and 70 ml of phosphorus oxychloride were boiled and heated for 2 hours. The dark brown suspension was evaporated to a remaining volume of 20 ml. The residue was added portionwise to water, neutralized with solid NaHC03, and 0.2 liter of ethyl acetate was added thereto. Filtration and rinsing with hot THF gave the title compound; ^ H-NMRpOO MHz, DMSO-d6): 13.2 (sb, 1H), 8.72 (d, J = 7 .. 1H), 8.63 (s, 1H), 8.23 (d, J = 11, 1H), 7.97 (U = 11, 1H), 7.46 (d | J, = 7, J2 = 11, 1H), 7.35 (s, 1H). Further product can be isolated from the filtrate and THF washing solution, evaporated and concentrated, partitioned between ethyl acetate / water, and digested in ethyl acetate / ether. Example 2: Hydrochloric 4- (3-chloro-aniline) -6- (pyridin-2-yl) -7H-pyrrole 幷 2,3-by pyrimidine: This paper size applies to Chinese National Standard (CNS) Λ4 specification (210X 297mm) AWI order (please read the precautions on the back before filling this page) -56- Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 1i 472057 A7 B7 ___ 5. Description of the invention () 4.6 mmol) 4- (3-chloro-aniline) -6- (pyridin-2-yl) -7H-pyrrolo [2,3-d] pyrimidine (see Example 1) suspended in 115 ml of dioxane ; Under cooling, 46 ml of a 0.1NHC1 solution (0.1 equivalent hydrochloric acid solution) was added, and the reaction suspension was stirred at room temperature for 2.5 hours. The suspension was concentrated by evaporation and the residue was stirred and filtered in 400 ml of hot methanol. The filtrate was filtered through activated carbon while hot, concentrated by evaporation, and digested in cold ethanol; melting point: 276-278 ° C; W-NMR (200 MHz, DMSO ~ d «): 13.1 and 10.7 (2s, 2H), 87.1 (4 J = 5, 1Η), 8.45 and 8.08 (2s, 2Η), 8.00 (take 2Η), 7.76 (cU = 8, 1Η), 7.68 (s, 1H), 7.50 ( &lt; U = 8, 1H), 7.42 (nUH), 7.27 (soil J = 8, 1H). Example 3: 4- (3-Chloro-aniline) -5-dimethylamine methyl-6- (pyridin-2-yl) -7H-pyrrolidine [2,3-dl pyrimidine 60.1 mg (0.325 mmol) of iodized N, N-dimethyl-methyleneimide (Fluka; Buchs / Switzerland) was added with 80.4 mg (0.25 mmol) of 4- (3-chloro-aniline) -6 · (pyridine 2-yl K7H-pyrrolo [2,3-d] pyrimidine (see Example 1) was dissolved in 3 ml of a solution of absolute tetrahydrofuran, and the reaction mixture was boiled under reflux for 3 days. The reaction mixture was subjected to ethyl acetate and Na2C03 The saturated solution was partitioned, and the inorganic phase was separated and extracted with 2 portions of ethyl acetate. The organic phase was washed three times with water and once with brine, dried over river 8804 and concentrated by evaporation. Ethyl acetate / ether Digestion yielded the title compound; melting point: 247-251. (:; W-NMR (300 MH & DMSO-de): 12.8 and 12.2 (2s, 2H), 8.71 (1H), 8.37 and 8.23 (2s, 2H) , 7.93 (Roar 1H), 7.80 ( &lt; U = 8, 1H), 7.47 (Table J = 8, 1H), 7.37 (m, 2H), 7.03 (d, J = 8, 1H), 4.18 (s, 2H), 2.40 (s, 6H) ; MS: (M) + = 378. Example 4 4- (3-Amo-4-gas-aniline) -6- (P ratio steep-2-yl) -7H-H ratio slightly 幷 2,3-d ~ China National Standard (CNS) Λ4 specification (2Ι0χ 297 cm) --------- ΦΓ ^. | 丨 (Please read the precautions on the back before filling this page) Order-57- 472057 A7 B7 V. Description of the invention () Under a protective gas, 20 mg (0.09 mmol) of 6- (fl ratio lake-2-yl) -7H-B is more than [2,3-d] pyrimidine- 4-Alcohol (see step 1.2) is boiled with 1 ml of phosphorus oxychloride for 30 minutes. The reaction mixture was concentrated by evaporation to dryness and prepared as a suspension in 1 ml of n-butanol. 16.4 mg (0.108 mmol) of 3-chloro-4 · fluoro-aniline was added and the suspension was boiled under reflux for 2 hours. The dark brown suspension was then concentrated by evaporation and the residue was dissolved in methanol. Add silicone and dry. The powder was packed into a silica gel column and eluted with ethyl acetate to give the title compound; W-NMR (400 MHz, DMS0-4): 12.5 (sb, HN), 9.64 (s, HN), 8.64 (d , J = 5, 1H), 8.38 (s, 1H), 8.35 (dd, J! = 7, J2 = 3, 1H), 7.92 (m, 2H), 7.83 (m, 1H), 7.53 (s, 1H ), 7.41 (t, J = 9, 1H), 7.33 (m, 1H); HPLC: tRet (Grad2〇) = 10.4; MS: (M) + = 339. Example 5: 4- (3-Chloro-aniline) -5-methyl-6- (pyridin-2-yl) -7H-pyrrole, 2,3-d, pyrimidine and 4- (3-chloro- Aniline) -5-methyl-6- (N-benzyl-pyridin-2-yl) -7H-pyrrolo [2,3-d] Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (Please read the Note for refilling this page) Add 529 μl (5.0 mmol) of 3-chloro-aniline to approximately 1.2 mmol of 4-chloro-5-methyl-6- (N-benzyl-pyridine-2) with the air removed -Yl) -7H-pyrylopyridine [2,3-d] pyrimidine was dissolved in 10 ml of a solution of isopropanol, and the reaction mixture was boiled under reflux for 3 hours. The reaction mixture was concentrated by evaporation and the residue was subjected to silica gel chromatography. Dilute with dichloromethane / ethanol (7: 3) and dichloromethane / methanol (7: 3) to produce 4- (3-chloro-aniline) -5-methyl-6- (pyridin-2-yl) first 7H-pyrrole [2,3-d] pyrimidine (A), which then produces 4- (3-chloro-aniline) bromide> 5-methyl-6- (N-benzyl-pyridin-2-yl)- 7H-pyrrolo [2,3-d] pyrimidine (B). (A) can also be obtained by heating (B). (A): melting point: 251-252 ° C; W-NMR (200 MHz ^ DMSO-d ^): 12.75 and 9.25 (2sb), 8.75 ( &lt; U = 5, 1H), 8.35 (s, 1H), 8.05-7.85 (m, 3H), 7.66 (d, J-8, 1H), 7.45 (m, 2H), 7.29 (d, J = 8 , 1H), 2.84 (s, 3H); FAB-MS: (M + H) + = 336. (B): Melting point: 171-172 ° C (strongly issued paper standards are applicable to Chinese National Standards (CNS) Λ4 specifications (21 × 297 mm) -58- 472057 A7 B7 Printed by the Consumer Standards Association of the Central Standards Bureau Description of the invention () Bubble); h-NMR (200 MH &amp; DMSO-Mountain): 12.65 (sb), 9.48 (丨 J = 6, 1H), 8.80 (t, J = 8, 1H), 8.59 (sb, 1H), 8.43 (s, 1H), 8.3 (m, 2H), 7.94 (m, 1H), 7.72 (d, J = 8, 1H), 7.40 (t, J = 8, 1H), 7.28 (m, 3H), 7.17 (d, J = 8, 1H), 6.94 (m, 2H), 5.93 (s, 2H), 2.27 (s, 3H); FAB-MS: (M + H) + = 426. The starting materials are prepared as follows: Step 5.1: Tritiated 2- (5-amine cyanocyanate-3-methyl-1pyroyl-2-pyrrol-2-yl) -N-benzyl-pyridine under argon pressure, 1.81 g (5.5 mmol) N-benz-2-bromo · I This ingot [for preparation method see J. Heterocyclic Chem. 28, 1083 (1991)] Add 605.5 mg (5.0 mmol) of 2-amine-3-cyano-4 -Methyl-pyrrole [see Preparation of Synthesis (1976), 51] in 40 ml of dichloromethane and 639 µl (5.5 mmol) of dimethylpyridine. After stirring at room temperature for 5.5 hours, the reaction mixture was concentrated by evaporation to approximately half its original volume. The suspension was filtered and washed with dichloromethane / ethyl acetate (1: 1) and ethyl acetate / hexane (1: 1) to give the title compound; 1H-NMR (300 MHz, DMSO-de): 10.83 (s, 1H), 9.10 (4 J = 7, 1H), 8.49 (t, J = 7, 1H), 7.96 (m, 2H), 7.30 (m, 3H), 6.95 (m, 2H), 6.57 R 5.80 (2s' 2H each), 1.76 (s, 3H); FAB-MS: (M + H) + = 289. Love_ ^ 5 · 2: 5-methyl-6-ΓΝ-benzyl-pyridine_2-yl) -7H-pyrrole 幷 2,3-dlpyrimidine · 4-ol under a protective gas, 1.182 g ( 3.2 mmol) A solution of 2- (5-amine_4_cyano-3-methyl-1H · pyrrole-2-ylbenzyl-pyridine) in 12 ml of formic acid was heated at 110 ° C for 90 minutes. The reaction mixture was concentrated by evaporation, and the residue was freeze-dried from water, and finally freeze-dried twice from dioxane containing a small amount of water to give the title compound; 1H-NMR (200 MHa DMSO ~ d «): 12.0 (sb), 9.40 (d, J = 8,! Η), 8.73 (t, J = 8, 1H), 8.25 (m, 2H), 7.98 (s, 1H), 7.27 (m, 3H), 6.90 (m, 2H), This paper size applies the Chinese National Standard (CNS) Λ4 specification (21 OX 297 mm) (Please read the notes on the back _ —0. • Items are then filled. Installation —: Write this page) Order -59- 4, „ 472057 Revised Page of Chinese Specification for Patent Application No. 85108440 (July 88) '^;-&quot; 1 &quot; ::: xiaonei $ Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of Invention () 5.92 ( s, 2H), 2_04 (s, 3H); HPLC tRet (20) = 5.8 minutes; FAB-MS: (M + H) + = 317. Step 5.3: 4-Chloro-5-methyl-6- (Nf -P 比 淀 -2-yl HH- 卩 比 幷 幷 2J-dl pyrimidine 500 mg (1.2 mmol) 5-methyl-6- (N-benzyl-pyridyl) 7H -Pyrrolidine [2,3-d] pyrimidine alcohol and 15 ml of phosphorus oxychloride were boiled for 2 hours. The reaction mixture was concentrated by evaporation to give the title compound; HPLC: tRet (Grad2〇) = 8.8; FAB-MS: ( M + H) + = 335 ^ Example 6 ♦ 4- (3- 氛 ~ 4-4-- 本 amine) -5-methyl-6- (卩 比 陡 -2-yl) -7Η-ί! 比 略 幷丨 2,3-d | The title compound was sprayed by the method of Example 5 using 3-chlorofluoro-aniline; melting point: 277-278 ° C; W-NMR (300MHz, DMSO〇9.3 (sb), 8.73 (d, J = 5, 1H), 8.33 (s, 1H), 7.96 (m, 2H), 7.88 (d, J = 8, 1H), 7.67 (m, 1H), 7.52 (t, J = 9 , 1H), 7.40 (% 1H), 2.83 (s, 3H); MS: (M) + = 353. Reference Example 7: 4- (3-Gas-aniline) -7H-pyrrolo [2,3-dl pyrimidine 133 mg (0.866 mmol) 4-chloro-7H-pyrrolo [2,3-d] pyrimidine [Preparation method: Chem. Ber. 112, 3526 (1979)] and 136 microliters (1.3 mmol) of 3-chloro-aniline were boiled in 4 ml of n-butanol for 90 minutes. The dark green reaction solution was diluted with ethanol and filtered through activated carbon while hot. Concentrated by evaporation ', stirred in isopropanol, filtered and recrystallized from hot isopropanol with a small amount of ethanol to yield the title compound; melting point: 230-233 ° C; 12.5 and 10.7 (2sb, 2H), 8.42 ^ 7.97 (2s, 2H), 7.67 (d, J = 8, 1H), 7.48 (t, J = 8, 1H), 7.43 (m, 1H), 7.29 (d, J = 8, 1H), 6.93 (sb , 1H); FAB-MS: (M + H) + = 245 = Example 8: 4- (3-Chloro-aniline) -6- (biphenyl_4-yl V7H-pyrrole) 2,3-dl Pyrimidine (Please read the precautions on the back before this page)-Binding and binding papers are applicable to Chinese National Standards (CNS) Λ4 Grid (llOXW) -60- 472057 Α7 Β7 Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economy Preparation 5. Description of the invention (1) 220 mg (0.72 mmol) of 4-chloro-6- (biphenyl-4-yl K7H-pyrrolo [2,3-d] pyrimidine and 151 microliters (1.44 mmol) A suspension of 3-chloro-aniline in 5 ml of butanol was boiled and heated overnight. Cooled, filtered and washed with a small amount of ethanol, and finally washed with hexane to give the title compound; W-NMR (200 MHz, DMSO- de): 12.46 (sb, 1H), 9.6 (s, 1H), 8.40 (s, 1H), 8.28 (m, 1H), 7.98 (d, J = 8, 2H), 7.8 (Roar 5H), 7.52 and 7.38 (2t J = 8, 2H each), 7.30 (s, 1H), 7.08 (db, J = 8, 1H); MS: (M) + = 397. The starting materials were prepared as follows : Step 8. 1: 2 · Amine-3-ethoxycarbonyl-5- (biphenyl · 4-yl) -1Η · Pyrile Under argon pressure, 1.65 g (10 mmol) of 2-methyl hydrochloride Pyrene-ethyl acetate [see preparation method: Liebigs Ann. Chem., 1895 (19 &quot; 77)] was added to 10 ml of ethanol, and 0.73 g (10 mmol) of sodium ethoxide was added thereto at 0-5 ° C. The bright yellow suspension was stirred for 20 minutes, then 1.4 g (5 mmol) of 2-bromo-1- (biphenyl-4-yl &gt; ethyl-1-one (2-bromo-4'-benzene-benzene Ethyl ketone; Aldircli; Milwaukee / United States) was added thereto. After stirring at room temperature for 48 hours, the reaction mixture was concentrated by evaporation, and the residue was dissolved in ethyl acetate and rinsed with 3 portions of water and brine. The aqueous phase was extracted twice with ethyl acetate, and the organic phase was dried over 18804 and concentrated by evaporation. Performed column chromatography (Si02; ethyl acetate / hexane [1: 1]) and stirred in isopropyl ether / hexane to give the title compound; melting point: 186-188 ° C; TLC-Rr = 0.17 (Ethyl acetate / hexane [1: 1]); FAB-MS: (M + H) + = 306. Step 8.2: 6- (biphenyloxy) -7H-pyrrolidinium 2,3-sanpyridolol at 150 ° C, change 7 from mg (2.5 mmol) of 2-amine to each ethoxycarbonyl- 5- (biphenyl · 4-yl) · 1Η-pyrrole in 5 ml of formamidine, 2.5 ml of DMF and 1.25 ml of formazan --------- · Packing -----, -ITJ ·- --- Φ (Please read the notes on the back before filling in this page) This paper size applies to Chinese National Standard (CNS) A4 (210 '乂 2 mm) -61-472057 Employees' Cooperatives, Central Bureau of Standards, Ministry of Economic Affairs Print A7 B7 5. Description of the invention () Stir in acid for 20 hours. Dilute the reaction mixture with isopropanol and filter. Rinse with isopropanol and hexane to give the title compound. Melting point> 300 ° C; FAB- MS: (M + H) + = 288 ° Step 8.3: 4-Chloro-6- (biphenyl-4-yl) -7H-pyrrole 幷 2,3-d〗 Pyrimidine under a protective gas, 430.5 mg (1.5 mmol) 6- (biphenyl "4-yl) -7H-pyrrolo [2,3-d] pyrimidine * 4-alcohol dissolved in 6 ml of phosphorus oxychloride and boiled for 4 hours. Reaction mixture Pour into ice water and ethyl acetate. The aqueous phase is separated and extracted with ethyl acetate. The organic phase is concentrated by evaporation and The residue was stirred in hot THF / isopropanol to give the title compound; melting point: 295 _ 300 ° C (decomposition); FAB-MS: (M + H) + = 306. Example 9: 4- (3-chloro -Aniline) ~ 6- (naphthalene-2-yl)> 7H-pyrrolidinium 2,3 ~ dl pyrimidine 98 mg (0.35 mmol) 4 · chlorowood (Tethy-2-yl)> 7iWl ratio slightly [ A solution of 2,3-d] pyrimidine and 73 μl (0.7 mmol) of 3-chloro-aniline in 8 ml of butanol was boiled and heated for 5 hours. Cooling, filtering and washing with isopropanol and hexane gave the title Compound; melting point: 278-284 ° C; TLC-Rf = 0.5 (ethyl acetate / hexane [1: 1]); FAB-MS: (M + H) + = 37]. The starting materials were prepared as follows: Step 9.1: 2-amine-3-ethylargonyl-5- (tidyl V1H-pyrrole under argon pressure, 834 mg (5 mmol) of 2-formamidine-ethyl acetate hydrochloride [for preparation method see: Liebigs Ann. Chem., 1895 (1977)] was added to 10 ml of ethanol, and 358 mg (5 mmol) of sodium ethoxide was added thereto at 0-5 ° C. The bright yellow suspension was stirred for 15 minutes, and then 623 mg (2.5 mmol) 2-bromo-1- (naphthalen-2-ylethyl-1-one (2-bromo-2, -naphthyl ethyl ketone; Aldirch; Mill) (US / USA) added. After stirring at room temperature for 3 days, this paper size applies Chinese National Standard (CNS) A4 specification (210X297 male flood) ΜΗΜΒ ΜΜΗΒΒ-* Ji tLW— · nn (Please read the precautions on the back first (Fill in this page again) -62- Printed by the Staff Consumer Cooperative of the Central Bureau of Standards, Ministry of Economic Affairs 472057 A7 B7__ 5. Description of the invention () The reaction mixture is evaporated and concentrated. The residue was dissolved in ethyl acetate / water and filtered, and the organic phase was separated and washed with 3 portions of water and brine. The aqueous phase was extracted with ethyl acetate 'and the organic phase was dried over MgS04 and concentrated by evaporation. Actual column chromatography (SiO2; ethyl acetate / hexane [1: 1]) and stirring in ether / hexane to give the title compound; melting point: 149-151 ° C; TLC-Rf = 0.5 (ethyl acetate / hexane [1: 1]); FAB-MS ... (M + H) + = 281. Step 9.2: 6- (naphthalene · 2-yl) -7H-pyrrole 幷 2.3-dl pyrimidinol at 150 ° C, 420 mg (1.5 mmol) of 2-amine-3-ethoxyquin-5- (Montan-2-yl) -1H-1 This was stirred in 3 ml of formamidine, 1.5 ml of DMF and 0.75 ml of formic acid for 22 hours. The reaction mixture was diluted with approximately 1 ml of isopropanol and filtered. Rinse with ethanol, isopropanol, and hexane to give the title compound; melting point> 300 ° C; ^ -NMR (200 MHz, DMSO- ^): 12.2 (sb), 8.39 (s, 1H), 8.0 (m , 2H), 7.9 (H 3H), 7.53 (take 2H), 7.11 (s, 1H) »Step 9.3: 4-Chloro-6 · (naphthalene ~ 2-yl) -7H-pyrrole 幷 2,3-dl A solution of pyrimidine (198.5 mg (0.76 mmol) 6 · (Mongol 7Η-pyrrolo [2,3-d] pyrimidino 4-ol) in 3 ml of phosphorus oxychloride was boiled for 5 hours under a protective gas. The reaction mixture was poured into ice water and stirred for 1 hour to complete the reaction. The crystals were filtered off and washed with water. The crude product was dissolved in THF / methanol, filtered through activated carbon, the filtrate was concentrated by evaporation, and the residue was in isopropyl Stir in alcohol and wash with hexane to give the title compound; melting point: 268 -269 ° C (decomposition); FAB-MS: (M + H) + = 280. Example 10: Tritiated 4- (3- Chloro-aniline V6- (2-mer-benzene) -7H-pyrrole, 2,3-dl pyrimidine, 6.72 g (19.16 mmol) 4- (3-chloro -Aniline> 6- (2-methoxy-benzene)> 7H-pyrrolo [2,3-d] pyrimidine added to 150 ml of two papers Home Standard (CNS) eight 4 Specifications (2 Shu OX297 mm) I I »n loaded -L - ^ w_ ^ (Please read the notes on the back of this page and then fill in) -63-472057

Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention () In methyl chloride. Under ice-cooling, a solution of 18.4 ml (191.6 mmol) of boron tribromide in 100 ml of dichloromethane was added dropwise thereto over 1 hour. After stirring for 3 hours in an ice bath, the suspension was poured into 0.5 liters of ice water and filtered. The residue was dissolved in ethyl acetate and washed with a saturated solution of NaHC03, water and brine. The aqueous phase was extracted twice with ethyl acetate, and the organic phase was dried over MgS04, evaporated and concentrated, and crystallized from ethanol / hexane to give the title compound; 1H-NMR (300 MH2; DMSO-Yu): 8.41 (s , 1H), 7.92 (s, 1H), 7.78 (d, J = 8, 1H), 7.64 (d, J = 8, 1H), 7.50 (m, 2H), 7.35 (d, J = 8, 1H) , 7.23 (m, 1H), 7.04 (d, J = 8, 1H), 6.59 (dd, J = 8, 1H); FAB-MS: (M + H) + = 337. The starting materials are prepared as follows: Step 10.1: 2-Amine-3-ethoxycarbonyl-5- (2-methoxy-benzene V1H-pyrrole) Using a method similar to step 8.1, make 14.5 g of 150 ml of absolute ethanol ( 87 mmol) 2-formamidine-ethyl acetate hydrochloride with 5.9 g (87 mmol) of sodium ethoxide and 10.3 g (44 mmol) of 2-bromo-1- (2-methoxy-benzene) -ethyl- 1 · ketone (2 · bromo-2'-methoxy-acetophenone; Aldrich; Milwaukee / United States) reaction to form the title compound; melting point: 128 ° C; TLC-Rf = 0.25 (hexane / acetic acid Ethyl [2: 1]). Step 10.2: 6- (2_methoxy-benzene) _7H-pyrrole 幷 2,3-dlpyrimidine ~ 4_ol under a protective gas, 7.66 g (31 mmol) ) 2 · Amine-3-ethoxy curtain-5- (2-methoxy-benzene) -1Η-pyrrole dissolved in 63 ml of formamidine, 31.5 ml of DMF and 7.7 ml of formic acid at 15 ° C It was heated overnight. After subsequent treatment using a method similar to step 8.2, the title compound was produced; TLC-Rf = 0.33 (hexane / ethyl acetate [U]). The paper size applies to the Chinese National Standard (CNS) Λ4 specification (210X29 &quot;; Public record;) --------- install -----,-order I L ----- (Please read the notes on the back first (Fill in this page again) -64- Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs 472057 A7 B7 V. Description of the invention () Step 10.3: 4-Chloro-6 · (2-methoxyso h7Hife.ro 幷 [2,3 -Introducing pyrimidine under argon, 6.2 g (25.7 halo: mole) of 6- (2-methoxy ·· benzene) -7H-B is slightly higher than [2,3-d] pyrimidine + alcohol and 62 ml of oxygen The chloride was heated at 125 ° C for 1.5 hours. The reaction mixture was poured into ice water 'and extracted three times with ethyl acetate. The organic phase was washed with water, NaHC03 solution and brine, dried over MgS04 and concentrated by evaporation. The silica gel column was filtered with ethyl acetate to give the title compound; TLC-Rf = 0.8 (hexane / ethyl acetate [1: 1]). Step 10.4: 4- (3-chloro-aniline) -6 ~ (2- Methoxy-benzene V7H-pyrrole [2,3-dl pyrimidine] 6.6 g (25.4 mmol) 4-chloro-6 · (2-methoxy-benzene) · 7Η-pyrrole [2,3-d] pyrimidine And 5.34 ml (50.8 mmol) of 3-chloro-aniline in 100 ml of n-butanol was boiled and heated for 1.5 hours. The reaction mixture was cooled, then filtered and washed with ether and hexane. Flash chromatography (Si02 ; Dry use; hexane / ethyl acetate [2: 1]-ethanol / acetone [1: 1]), yielding the title compound; melting point: 221 -222 ° C; TLC-Rf = 0.3 (hexane / ethyl acetate [1: 1]); FAB-MS: (M + H) + = 351 »Example 11: 4- (3 ~ chloro-aniline) ~ 6 ^ 3 met-benzene V7H-pyrrole f2,3-dl pyrimidine using a method similar to that in Example 10, 150 ml of dichloromethane 4.53 g (12.91 mmol) of 4- (3 · chloro-aniline) -bu (3-methoxy-benzene)> 7H_I this slightly [2,3-d] pyrimidine and 150 ml of methylene chloride 12.4 ml (129 mmol) Boron tribromide was reacted to form the title compound; 1 ^: ^ (0 ^ 2〇) = 10.5 minutes; 111-NMR (500 \ 1 from DMSO-d «): 12.61, 10.07 And 9.68 (3sb, 3H), 8.35 (s, 1H), 8.09 (s, 1H), 7.76 (d, J = 8, 1H), 7.39 (dd, J = 8, 1H), 7.27 (m, 2H) , 7.23 (s, 1H), 7.12 (1H), 7.11 (s, 1H), 6.77 (m, 1H). The starting materials are prepared as follows: This paper size applies the Chinese National Standard (CNS) A4 size (210X 297 mm) ml ml it I ί nn m nn HI V'Jm ^ im mu (Please read the precautions on the back before reading (Fill in this page) -65- 472057 A7 B7 printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs 5. Description of the invention () Step 11.1: 2-Amine-3-ethoxyquin-5- (3-methoxy-benzene ratio Using a method similar to step 8.1, 14.5 g (87 mmol) of ethyl 2-formamidine hydrochloride in 150 ml of absolute ethanol was mixed with 5.9 g (87 mmol) of sodium ethoxide and 10.3 g (44 mmol) of Mole) 2-bromo- (3-methoxy-benzene) -ethan-1-one (2-bromo-3 '• methoxy-acetophenone; Janssen) reacts to form the title compound; melting point:% -97 ° C; TLC-Rf = a2 (hexane / ethyl acetate [2: 1]). Step 11.2: 6 ~ (2-methoxy-benzene V7H-pyrrole 幷 2,3-d) pyrimidinol in one protection Under a gas, a solution of 7.19 g (29 mmol) of 2-amine; ethoxy-5--5- (3-methoxy-benzene) -1Η-pyrrole was dissolved in 59 ml of formamidine, 29.5 ml of DMF, and 14.7 ml of formic acid. Heat overnight at 150 ° C. Follow-up using a method similar to step 8.2 After the treatment, the title compound was produced; TLC-Rf = 0.3 (hexane / ethyl acetate [1: 1]). Step 11.3: 4-chloro-6- (3-methoxy-benzene) -7H-pyrrole 幷 2 , 3-d] Pyrimidine With the exclusion of water, 5.28 g (21.9 mmol) of 6- (3-methoxy-benzene) -7H-pyrrolidine P, 3-d] pyrimidine 4 alcohol and 53 ml of oxychlorination Phosphorus was heated for 1.5 hours. The reaction mixture was cooled and filtered. The residue was dissolved in ethyl acetate and washed with NaHC03 solution, water and brine. The aqueous phase was extracted once with ethyl acetate, dried with ^ 804 and evaporated. Concentrate to form the title compound; TLC-Rf = 0.73 (hexane / ethyl acetate [1: 1]). Step 11.4: 4- (3-chloro-aniline) -6- (3-methoxy-benzene V7H-pyrrole幷 丨 2,3 ~ dl pyrimidine will be 5.68 g (21.9 mmol) 4-chlorodong (3-methoxy-benzene K7H-pyrrole [2,3-d] pyrimidine and 4.59 ml (43.7 mmol) ) The solution of 3-chloro-aniline in 75 ml of n-butanol is boiled and heated for 1.5 hours. Use the method similar to step 10 · 4 to follow up II binding II (please read the precautions on the back before filling this page) This paper Standards apply to Chinese National Standard (CNS) Λ4 specifications (2 丨 0 × M7 mm) -66- Ministry of Economic Affairs Printed by the Consumer Standards Cooperative of the Central Bureau of Standards 472057 A7 _B7 V. Description of the invention () Processed to produce the title compound; melting point: 262-263 ° C; FAB-MSJM + t ^, 35 Example 12: Hydrobromide 4 ~ ( 3-Chloro-aniline) -6 ~ (4-Chloro-benzene) · 7Η-pyrrole3-Z3-dl knee 砬 Dissolve 6 ml of boron tribromide at 100 ° C at a temperature of about 0 ° C. In 40 minutes of dichloromethane solution, 2.0 g (5.7 mmol) of 4- (3-chloro-aniline) -6- (4-methoxy-benzene) -7H-B was added slightly [2,3 -d] Chew dissolved in 60 ml of dichloromethane. After stirring at room temperature for 21 hours, the reaction mixture was filtered. The crude product was precipitated from the filtrate with about 1 liter of hexane, filtered off, and washed with hexane. The residue was dissolved in 0.2 liters of water and 0.6 liters of ethyl acetate, and neutralized with a 5% NaHC03 solution. The organic phase was separated, washed with water and brine, dried over MgS04 and concentrated by evaporation. Crystallization from hot methanol with hexane yielded the title compound; elemental analysis calculated for C18H14N4OBrCl (+ 0.13H2O): C 51.47%, Η 3.36% »N 13.34%, Br 19.02%, α 8.44%; Experiment 値: C 51.58% Η 3.32% »Ν 13.37%» Br 19.29 ^ Cl 8.46%; W-NMR (360 ΜΗζ ^ DMSO-Mountain): 12.85 and 10.60 (2sb, 2Η), 10.5-9.5 (sb), 8.37 (s, 1Η), 7.92 (s, 1H), 7.67 (d, J = 8, 2H), 7.63 (d, J = 8, 1H), 7.51 (dd, J = 8, 1H), 7.33 (d, J = 8 , 1H), 7.06 (s, 1H), 6.90 (d, J = 8, 2H) ° The starting materials are prepared as follows: Step 12.1: 2 • amine-3-ethanecarbonyl-5 · (4-methoxy- Benzene V1H-pyrrole Using a method similar to that in step 8.1, 167 g (10 mmol) of 2-formamidine-ethyl acetate in 20 ml of absolute ethanol and 716 mg (10 mmol) of sodium ethoxide and 1.145 G (5.0 mmol) of 4-methoxy · benzamidine methyl bromide (Fluka; Buchs / Switzerland) reacted to form the title compound; soluble --------------. I1TI "----- (Please read the precautions on the back before filling this page) This paper size applies to Chinese national standards (CNS> Λ4 specification (210X 297 cm) -67- 472057 Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A 7 B7 V. Description of the invention () Point: 141-142 ° C; TLC-Rf = 0.4 (hexane / ethyl acetate [1: 1]); FAB-MS: (M + H) + = 261 ° Step 12.2: 6- (4-methyl-benzene) -7Η-pyrrole 幷 2,3-d 611 mg (2.3 mmol) of 2-amine-3-ethoxy curtain-5 · (4-methoxy-benzene) 1H-pyrrole dissolved in 5 ml of formamidine, 2.5 ml of DMF and 1.25 ml of formic acid at 150 It was heated overnight at ° C. After subsequent processing using a method similar to step 8.2, the title compound was produced; melting point> 300 ° C; FAB-MS: (M + H) + = 242 ° step 12.3: 4-chloro-6- (4-methoxy-benzene V7H-pyrrole, 2,3-dl pyrimidine, excluding water, 121 mg (0.50 mmol) 6 · (4 · methoxy-benzene) · 7Η-pyrrolidine [2 3> D] pyrimidine &gt; 4-ol and 1 ml of phosphorus oxychloride were boiled and heated for 1.5 hours. The reaction mixture was poured into ice water and extracted twice with ethyl acetate. The organic phase was washed three times with water and brine, dried over MgS04 and concentrated by evaporation. The residue was stirred in diethyl ether to give the title compound; melting point: 248-249 ° C; FAB-MS: (M + H) + = 260. Step 12.4: 4 ~ (3-Chloro-aniline V6- (4-methoxy-benzene) -7H-pyrrole [2,3-dl pyrimidine] 95 mg (0.365 mmol) 4-chloro-6- (4- Methoxybenzene) · 7Η-Pyrrolidine [2,3-d] pyrimidine and 77 microliters (0.732 mmol) of 3-chloro "aniline dissolved in 3 ml of n-butanol and a few drops of DMPU were boiled for 2 hours. The reaction mixture was cooled, diluted with diethyl ether and isopropanol, and filtered; melting point: 294-295 ° C; FAB-MS: (M + H) + = 351. Example 13: 4- (3-chloro-aniline)> 5 -Dimethylamine-6- (4-hydroxy-benzene V7H-pyrrole) 2,3-dl pyrimidine This paper size is applicable to Chinese National Standard (CNS) Λ4 specification (210 X 297 mm) -68- ϋ— nm ^ ln ^ in ^ f — ^ ϋ 1 m HI n · ^ »v -I — ^ ϋ m (Please read the notes on the back before filling out this page) 472057 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention () Under a pressure of argon,% .2 mg (0.52 mmol) of iodized N, N-di-shen-methylene yaqian (Fluka company; Buchs / Switzerland) was added to 134.7 mg (0.4 mmol) ) 4- (3-Chloro-aniline) -6 · &lt; 4-hydroxy-benzene &gt; 7H-pyrrolo [2,3-d] pyrimidine dissolved in 4.8 ml of absolute tetrahydrofuran Solution, and the reaction mixture was boiled at reflux for 1.5 hours. Followed by a method similar to that described in Example 3 and recrystallized from hot ethanol to give the title compound; melting point: 269-271 ° C; TLC-Rf = 0.31 (CH2C12 / methanol [10: 1]); MS: (M) + = 393; &quot; H-NMR (500 MHz, DMSOde): 12.48, 11.91 and 9.75 (3s, 3H), 8.32 and 8.25 (2s, 2H ), 7.40 winds J = 8, 1H), 7.34 (1H), 7.32 (d, J = 8, 2H), 7.00 (d, J = 8, 1H), 6.89 (d, J = 8, 2H), 3.72 (s, 2H), 2.36 (s, 6H). Example 14: 4- (3-chloro-aniline) -5-dimethylaminemethyl-6-benzene-7H-pyrrole Under argon pressure, a solution of 898.2 mg (2.80 mmol) 4- (3-chloroaniline) and 6-benzene-7H-I [2,3-d] J amidin in 33.6 ml of absolute tetrahydrofuran Boiling under reflux overnight with 673.4 mg (3.64 mmol) of N, N-dimethyl-methyleneimide (Fluka; Buchs / Switzerland). The reaction mixture was partitioned between ethyl acetate and 1N (= -equivalent) hydrochloric acid. The organic phase was separated and washed three times with water. The aqueous phase was back-extracted once with ethyl acetate and made alkaline with solid sodium carbonate to form a suspension. Ethyl acetate was added thereto, at which time the solids in the organic phase became concentrated. The organic phase was washed three times with neutral water and neutralized, and the aqueous phase was back-extracted with ethyl acetate. The collected organic phase (suspension) was concentrated by evaporation. The residue was stirred in diethyl ether to give the title compound; MS: (M) + = 377; b-NMR (200 MHz * DMSO-de): 12.57 and 12.12 (2s, 2H), 8.38 (s, 1H), 8.29 (m, 1H), 7.55 (m, 4H), 7.5-7.3 (m, 3H), 7.04 (dm, J = 8, 1H), 3.79 (s, 2H), 2.38 (s, 6H). This paper size applies Chinese National Standard (CNS) Λ4 specification (2 丨 0X297 公 漦> n — ^^^ 1 I nn 11 * m nn dn HI ml nn mu TJ nn sfon ^ it— mm ---- (please Read the notes on the back and fill out this page) -69- 472057 A7 B7 Central Standards of the Ministry of Economic Affairs 印 Printed by Employee Consumer Cooperatives V. Description of Invention () The starting materials are prepared as follows: 6-benzene · 7Η-ί 吐 晗幷 丨 2,3-dl pyrimidine · 4-ol 2.30 g (10 mmol) of 2-amine-3-ethoxycarbonyl-5-benzene_1Η · pyrrole under a protective gas [see preparation method: Syntiiesis, 272 (1987)] A solution of 20 ml of formamidine, 10 ml of DMF and 5 ml of formic acid was heated at 150 ° C for 24 hours. The reaction mixture was cooled and filtered, and the residue was washed with isopropanol / hexane. Wash. Stir in hot isopropanol to give the title compound; melting point> 300 ° C; FAB-MS: (M + H) + = 212. Step 14.2: 4- 氲 -6-Mo-7Η · P ratio slightly幷 [2,3-dl pyrimidine, with the exclusion of water, the ratio of 1.795 g (8.5 mmol) of 6 · benzene-7H-II to [2,3 &gt; d] pyrimidine · 4-ol and 27 ml of oxygen chloride Phosphorus was boiled for 3 hours. The reaction mixture was poured into ice water In the reaction, filtration and washing with hot isopropanol and β-alkane gave the title compound; FAB-MS: (M + H) + = 230. Step 14.3: 4_ (3_ambianiline &gt; 6-benzene-7H-pyrrole幷 丨 2,3-dl pyrimidine dissolved 1.251 g (5.45 mmol) of 4-chloro · 6-benzene-7H-pyrrole [2,3-d] pyrimidine and 1.15 ml (10.9 mmol) of 3-chloro-aniline Boiling in a suspension of 20 ml of n-butanol and 0.5 ml of DMPU for 2 hours. The reaction mixture was cooled and filtered. The residue was stirred in hot THF / methanol to give the title compound; melting point: 285-286. (:; FAB -MS: (M + H) + = 321. Example 15 (Reference Example): 4- (3-Chloro-aniline Vpyridine [1 ^ 呵 暌

This paper size applies to China National Standard (CNS) Α4 specification (210X29 * 7 public expense) -70- (Please read the notes on the back _ 4 _ before filling in. Packing —: write this page) Order 472057 Central Bureau of Standards, Ministry of Economic Affairs Printed by employee consumer cooperative A7 B7 V. Description of the invention () Add 5.7 g (15 mmol) of N-ice-free (3-chloro-aniline) -pyrimidine hydrazone [4,5-b] to a 7.6 g of anhydrous A1C13 Dissolve in 50 ml of toluene suspension and heat the reaction mixture at 100 ° for 45 minutes. Cool the reaction mixture to room temperature, pour into ice water, and stir for about 30 minutes to precipitate the crude product. The crude product was filtered off with suction filtration and washed with water. The filtrate was discarded. The crude product was dissolved in THF / ethyl acetate, washed with 5% sodium bicarbonate solution and saturated NaCl solution, dried and concentrated. When left to stand in a refrigerator, 4- (3-chloro-aniline &gt; pyrimidine 幷 [4,5-b] indole crystals were precipitated. The product was completely precipitated with cyclohexane. Further purification was performed in ethyl acetate Digestion was achieved to give the title compound as a slightly pink crystal; melting point> 260 ° C; W-NMRpeOMHz ^ DMSO-d ^): 12.20 (s, pyrrole NH), 8.97 (s, aniline NH), 7. 8.5 (take 8 aromatic hydrazone + pyrimidine hydrazone); FAB-MS: (Μ + Η) + = 295. HC1 salt will be 2.8 g 4- (3-Chloroaniline) pyrimidine hydrazone [4,5-b] indole dissolved in 400 ml of THF while hot and cooled to room temperature, and with stirring, 2.8 ml of HC1 in a 5M solution of ether was added Among them, after adding about 250 ml of ether and cooling in an ice bath, colorless crystals of hydrochloride 4 ~ (3 · • chloro-aniline) · pyrimidine 幷 [4,5-b] indole were precipitated, melting point: 280 -286 ° C. The starting materials were prepared as follows: Step 15.1: 4 · hydroxy-5.6-tetramethylene-7-benzyl-pyrrole 2 2,3-dl pyrimidine at 11 ° (: 15 g 2 -Amine-1-benzyl-3-cyano &gt; 4,5,6,7-tetrahydroindole (with 2-hydroxycyclohexanone, benzylamine and malononitrile as starting materials, prepared by known methods ( (See HJ Roth and K. Egdr, Arch. Pharmaz, 308, 179 [1975])) and boil with 100 ml of 85% formic acid for 5 hours. The reaction solution is cooled in an ice bath. The paper size is suitable for China. Standard (CNS &gt; Μ specifications (210X 297 cm) I ----- IU ----- (Please read the precautions on the back before filling this page) -71- 472057 A7 B7 V. Description of the invention () Light brown crystals precipitate. Pour the suspension into about 200 ml of ice water and stir for about 10 minutes. The precipitate was then filtered off by suction filtration. The crystals were washed with water and hexane and dried to give the title compound; melting point: 104-105 ° C; FAB-MS: (M + H) + = 280. Step 15.2: 4- (3-Chloro-aniline) -5,6-tetramethylene-7-benzyl-pyrrole, 2,3-dl pyrimidine, 0.65 g of 4-chloro-5,6-tetramethylene-7 -A solution of benzyl-pyrrolo [2,3-d] pyrimidine and 0.27 ml of 3-chloro-aniline in 10 ml of ethanol was heated at reflux for 17 hours. The brown solution was evaporated to dryness, and the residue was dissolved in ethyl acetate. The ethyl acetate solution was washed with sodium bicarbonate solution and water to make it neutral, dried and concentrated by evaporation. The residue was crystallized from ethyl acetate / hexane to give the title compound as white crystals; melting point: 145-147 ° C; FAB-MS: (M + H) + = 389. Step 15.3: N-benzyl-4- (3-chloro-aniline) nitridinoline is printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling this page). 14.1 g (62 mmol) ) 2,3-Dichloro-5,6-dicyano-I, 4-benzoquinone (DDQ) was added to a 12.1 g (3 mmol) of 4 &gt; (3-chloro-aniline &gt; 5,6 · Tetra Methyl-7-benzyl-pyrrolidine [2,3-d] pyrimidine was dissolved in a solution of 260 ml of toluene. The deep red solution was heated at reflux for 30 minutes, and then cooled to room temperature. The insoluble material was filtered off and used. The filtrate was concentrated by evaporation on a rotary evaporator. The crude product was chromatographed on silica gel (eluent with hexane / ethyl acetate) to give the title compound as colorless crystals; melting point: 174-176 ° C; W-NMR (360 CDC13): 12.20 (s, pyrrole NH), 9.0 (s, aniline NH), 7.0-8.6 (m, 13 aromatic pyrene and 1 pyrimidine H), 5.66 (s, 2H, benzyl); FAB- MS: (Μ + Η) + = 385. Example 16: Hydrobromide 4 ~ (3-chloro-aniline) -5-methyl-6- (4-hydroxy-benzene) -7Η-pyrrole 幷 2,3 -dl Pyrimidine This paper size applies Chinese National Standard (CNS) A4 (210X297 mm) -72- 472057 Λ7 B7 Central Ministry of Economic Affairs Standard Bureau employee consumer cooperatives ’printing bags V. Description of the invention () The title compound was obtained as a colorless powder in a manner similar to that in Example 10, and 5 g (6.85 mmol) of 4- (3-chloro · aniline) -5-form The methyl group in -6 · (4-methoxy-benzene) -7H-pyrrolo [2,3-d] pyrimidine was obtained by removing 4.4 g of boron tribromide in 30 ml of dichloromethane; melting point: 295- 296. (:; W-NMR (360 MΗ * DMSO-di): 11.85 (s, pyrrole NΗ), 9.68 (s, phenol H), 8.29 (s, aniline NH), 8.27 (s, pyrimidine Η) , 7.94 (m, aromatic H), 7.70 (m, aromatic H), 7.42 (d2 aromatic fluorene), 7.35 (t, aromatic fluorene), 7.06 (m, aromatic fluorene), 6.90 (4 2 aromatic Group Η), 2.58 (s, 3Η); FAB-MS: (Μ + Η) + = 35. HC1 salt To prepare HC1 salt, 600 mg of 4- (3-chloro-aniline) -5_hydrobromide -6- (4-Terbenylpyrrolidine [2,3-d] pyrimidine is dissolved in 50 ml of ethyl acetate while hot, and adjusted to pH 9.5 with INNaOH at room temperature, and the organic phase is taken up with water Rinse twice. The organic phase was dried and concentrated by evaporation, and the residue was dissolved in 30 ml of ethanol 'and a 5N (= 5 equivalent) HC1 ethanol solution was added thereto. At 〇. (: While stirring, add diethyl ether to obtain 4- (3-chloro-aniline) -5-methyl-6- (4 encounter benzene K7H-D ratio slightly benzene [2,3-d] Pyrimidine; Melting point: 280-282 ° C. The starting materials are prepared as follows: Step 16.1: 4-Chloro-5-methyl ~ 6 ~ (4-methoxy-benzene V7H ~ B ratio 幷 2,3- dltfidine uses a method similar to step 1.3, and the title compound is based on 4_hydroxy_5_methyl_6_ (4_methoxy-benzene K7H.! This slightly different [2,3-d] pyrimidine is used as the starting material. Obtained from boiling in phosphorus oxychloride; FAB-MS: (M + H) + = 274 〇 Step 16.4.2_ (3 · chloro-aniline) -5_methyl_6- (4_methoxy-benzene) _7Η · [Bab slightly 幷 丨 Nanduo will 4g 4_chloro_5_ 甲 -6 · (4_methoxy-benzene 丨-州-批 略 幷 Od) with a sharp mouth and 8.45ml of 3-chloro-aniline in 4 〇mL n-butanol was heated under reflux for 20 hours. The color-grabbing solution was concentrated, and the desired product had precipitated. The solution was stored in a refrigerator. This paper was scaled to the Chinese National Standard (CNS) Λ4 (210X 297) (Acid) (Please read the note on the back 'J0 • Item and fill it out. Pack —: Write this page) -Order _ -73-Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 472057 A7 B7 ___ ________________— 'V. Description of the invention () night, and the product was filtered off with suction filtration and washed with hexane / ethyl acetate to produce the title compound as colorless crystals; melting point: 265-268 ° C; FAB · MS: (M + H) + = 365. Example 17: The title compound of 4 · (3 · chloro · aniline V6 ~ (4-nitro-benzene) · 7Η · Lalan twist gAd] pyrimidine reddish brown crystal was used similarly In the method of Example 5, 0.25 g (0.91 mmol) of 4-chloro-6- (4_5Xiao-benzene) -7 ratio [Hd] pyrimidine and 0.19 ml of 3-chloro-aniline in 5 ml of n-butanol It is obtained by mid-boiling; melting point> 250 ° C; W-NMR (360 MHz ^ DMSO-di): 12.95 (s, pyrrole NH), 10.3 (s, aniline NH), 8.45 (s, pyrimidine), 8.24 ( s, aromatic fluorene), 7.18-8.4 (7 aromatic fluorene + pyrrole 5H); MS: (M) + = 365. The starting materials were prepared as follows: Step 17.1: 2-amine-3-ethoxycarbonyl-5 -(4 · Nitro-benzene VP ratio slightly_ In a dry three-necked flask, under argon, 75 ml of absolute ethanol and 6.5 g (390 mmol) of 2-formamidine-ethyl acetate hydrochloride [Preparation method See also: Liebigs Ann. Chem., 1895 (1977)], cooled to 0-5 ° C, and 2.65 g (390 mmol) of sodium ethoxide Join it. Then, 5 g (195 mmol) of 2-bromo-H4-nitro-benzene &gt; ethyl-1-one was added, and the reaction mixture was allowed to warm to room temperature 'and then stirred for 48 hours. The reaction mixture was then partitioned between water and ethyl acetate. The ethyl acetate phase was washed three times with water and once with a saturated NaCl solution, dried and filtered 'and the filtrate was concentrated by evaporation. The red-brown residue was suspended in hexane 'to precipitate the title compound as a crude product (purity 93%), which was used in the next step' without further purification; MS: (M) + = 275. Step 17.2: 4-jing-6- (4-per-benzene V7H-pyrrole 幷 2,3-dlpyrimidine This paper size applies to Chinese national standards (CNS &gt; Α4 size (2 丨 0 × 297 male) ----- --- Install-- (Please read the precautions on the back before filling this page) Order -74- 472057 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention () At 150 ° C, 2.5 G (97 mmol) of 2-amine-3-ethoxycarbonyl-5- (4-nitro-benzene) -pyrrole, 19.4 ml of formamidine, 9.7 ml of DMF and 3.1 ml of formic acid were stirred together for 22 hours. 1 ml of isopropyl Propanol was added to the hot reaction mixture. The reaction mixture was cooled and the precipitated product was filtered off. The product was washed three times with ethanol (10 ml each) and twice with isopropanol (10 ml each). And washed twice with hexane (10 ml each) to give the title compound as reddish brown crystals, which was used in the next step; MS: (M) + = 256. Step 17.3: 4-chloro-6 -(4-Nitro-benzene) -7H-pyrrolidinium 2,3-dlpyrimidine 4-chloro-6- (4-nitro-benzene) -7H-pyrrolidinium [2,3 -d] Pyrimidine is heated by 4-hydroxy-6- (4-nitro-benzene) -7H-pyrrole [2,3-d] pyrimidine was prepared with POC13 (purity 93%); melting point> 280 ° C; FAB-MS: (M + H) + = 275. Example 18: 4- (3-chloro-aniline ) -6- (4-Amine-benzene) -7H41 than pyrrolidine 丨 2,3-dl pyrimidine 150 mg (0.41 mmol) 4- (3-chloro-aniline) -6 at room temperature and normal pressure -(4-Nitro-benzene) -7H-pyrrolidin [2,3-d] pyrimidine in 20 ml of THF / methanol and hydrogenated with 50 mg of Raleigh nickel for 5 hours, the desired product has precipitated. Catalyst It was filtered off and the filtered residue was washed with hot THF. The filtrate was concentrated by evaporation to dryness. The crude product was purified by digestion several times in methanol and precipitated from THF / hexane to give the title as a light gray-brown crystal. Product; melting point> 290 ° C; W-NMRpeO MHz, DMSO-tip): 12.05 (s, pyrrole NH), 9.38 (s, aniline NH), 8.31 (s, pyrimidine hydrazone), 8.24 (s, aromatic H ), 7.80 (d, aromatic H), 7.53 (&lt; U aromatic hydrazone), 7.35 (t aromatic H), 7.05 (modal aromatic H), 6.9〇 (s, pyrrole 5H), 6.64 (module 2 Aromatic H), 5.35 (s, NH2); MS: (M) + = 335. Example 19: 4- (3-chloro-aniline) -911-11 pyridine 幷 3 ', 2': 4, 51 pyrrolidine 丨 2,3- (11 pyrimidine This paper size applies to Chinese national standards Matters CNS) Λ4 Specification (21〇Χ297 public Mei) (Please read the back of the note and then fill in this page) - installed ·

1T -75- 472057 A7 B7 V. Description of the invention ()

Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs under nitrogen pressure and stirring, a 0.034 g (0.166 mmol) of 4-chloro-9H-pyridine hydrazone [3 ', 2' ·· 4, 5] pyrrolidine [ A mixture of 2,3-d] pyrimidine (German Patent No. 1916050) and 0.524 ml (4.99 mmol) of 3-chloro-aniline was heated at 120 ° C for 1 hour. The reaction mixture was cooled to room temperature, and then 5 ml of ethanol was added thereto. After further cooling to 0 ° C, the reaction mixture was filtered, and the crystals were washed with ethanol and dried under high vacuum. The formed title compound was melted at &gt; 260 ° (:, EI-MS: M = 295 (C15H1 () aN5). Example 20: Using the method described in this application, the following compounds were obtained: a) Hydrogen chloride 4-benzylamine-5,6-dimethyl-7H-pyrrole [2,3-d] pyrimidine, melting point: 115-117 ° C, b) (R) -5,6-dimethyl · 4- [ (1-Benzene-ethyl) -amine] -7H-pyrrolidinium P, 3-d] pyrimidine, melting point: 206-208 ° C, c) (S) -5,6-dimethyl-4-[(l-benzene -B) -Amine] -7H-pyrrolidin [2,3-d] pyrimidine, melting point: 206 -207 ° C, mountain (11) -6- (4-amine-benzene &gt; 4-[(1_benzene -B) -amine] -711-pyrrolidin [2,3- (1] pyrimidine, melting point: 234 -235 ° C, FAB-MS: (M + H) + = 330 (using a method similar to Example 18 , Obtained by reduction of equivalent nitro compounds with Raleigh nickel), e) (S) -6- (4-amine-benzene) · 4-[(1-benzene-ethyl) -amine] -7H-pyrrole [2,3-d] Pyrimidine, melting point: 235 -236 ° C 'FAB-MS: (M + H) + = 330 (Using a method similar to that in Example 18, the equivalent nitro compound was reduced with Raleigh nickel To get), (Please read the note 4 on the back first, then fill in and install —: write this page) The size of the paper is applicable to the Chinese National Standard (CNS) Λ4 specification (210X 297 (Public money) -76- 472057 Printed by A7 B7, Shellfish Consumer Cooperative, Central Bureau of Standards, Ministry of Economic Affairs 5. Description of the invention () 〇6- (4-amine-benzene &gt; 4-benzylamine-711-pyrrole [2,3 -(1) Pyrimidine_ (Lee) $ _ 0 in the method of '® ^^ 18, which is obtained by reducing the equivalent nitro compound with Raleigh nickel)' g) 6- (4-amine-benzene) -4- [ (3-Chlorobenzyl) amine] -7H-pyrrolo [2,34] 1 ^ # (Produced by a method similar to that of Example 18, which was obtained by reducing the equivalent nitro compound with Raleigh nickel), h) (R) -6- (4-Amine-benzene) -4-[(1-methoxycarbonyl-benzyl)]-amine-7H-pyrrolo [2,3_d] pyrimidine, i) (S) -Amine-benzene M-[(1-methoxycarbonylbenzyl)]-amine-7H * D than 幷 [2,3-d] pyrimidine, j) 6- (4-Ethylamine-benzene &gt; 4- (3-Chloro-aniline) -7H-pyrrolo [2,3-d] pyrimidine, melting point> 310 ° C, MS: (M) + = 377, k) 6- (4-aminoformamidinemethoxy- Benzene) 4- (3-chloro · aniline) · 7Η-pyrrole [2,3-d] pyrimidine 'Melting point: 297-298 ° C, l) 6- (4-amine-benzene) -4- (3- (Methyl-amine) -7H-pyrrolidinium [2,3 pyrimidine, melting point: 288-290 ° C (obtained by reduction of the equivalent nitro compound with Raleigh nickel using a method similar to Example 18), m) 6- (4-amine-benzene) bucket (3 • chlorobenzyl-aniline y7H-pyrrole [2 , 3-d] pyrimidine, melting point &gt; 300 ° C 'MS: (M) + = 353 (obtained by reduction of the equivalent nitro compound with Raleigh nickel using a method similar to that in Example 18), η) 6 -Salacetamide-benzene) -4- (3-chloro-aniline) _7H-pyrrolopyrene [2,3-d] pyrimidine (preferably prepared by a method similar to that of Example 21), mp &gt; 3〇 ( rc, MS: (M) + = 377, 〇) 6- (3-amine-benzene) (3-chloro-aniline) _711_pyrrolo [23_ &lt; 1] pyrimidine, melting point: 293-295 C (using similar In the method of Example 18, obtained by reducing the equivalent nitro compound with Raleigh nickel), this paper 剌 t _ ^ (CNSU ^ ir (210x297 ^) (Please read the note on the back I #. Fill and install-: Write this page) Order Φ. -77- 472057 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention () p) 6- (4-Carboxymethoxy-benzene) 4- (3-Chloro-aniline) -7H-pyrrolo [2,3-d] pyrimidine, melting point: 305 -307 ° C, q) 6- (4- [benzyloxycarbonyl-methoxy] -benzene) -4- (3-Chloro-aniline) -7H-pyrrolidine [2,3-d] pyrimidine, melting point: 263 -265 ° C, r) 6 &lt; 3-Aminemethylmethoxy-benzene) · 4 · (3-chloro -Aniline) -7H-pyrrolo [2,3-d] pyrimidine, melting point: 283 -285 ° C s) 4- (3-Chloro-aniline) -6- (4-methoxycarbonylmethoxy-benzene) -7H-pyrrolo [2,3-d] pyrimidine, melting point: 262-264 ° C, t) 4 -(3-chloro-aniline) -6- (3-methoxycarbonylmethoxy-benzene) -7H-pyrrolo [2,3-d] pyrimidine, melting point: 225-227. . , U) 6-carboxy-4- (3-chloro-aniline) -7H-pyrrolo [2,3-d] pyrimidine, melting point &gt; 290 ° C, FAB-MS: (M + H) + = 289, v) 4- (3-Chloro-aniline) -6-ethoxycarbonyl-7H-pyrrolo [2,3-d] pyrimidine, melting point &gt; 290 ° C, FAB-MS: (M + H) + = 317 , W) 6-n-butylaminecarbonyl 4- (3-chloro-aniline) -7H_pyrrolo [2,3-d] pyrimidine, melting point: 282 -284 ° C, FAB-MS: (M + H) + = 344, X) 4- (3-Chloro-aniline) -6- (4-ethoxycarbonyl-benzene) -7H-pyrrolo [2,3-d] pyrimidine, melting point> 300 ° C, FAB- MS: (M + H) + = 393, y) 6- (4-carboxy-benzene) -4- (3-chloro-aniline) -7H-pyrrolo [2,3-d] pyrimidine, melting point> 300 ° c, Rf = 0.47 (ethyl acetate / methanol [6: 4]), z) 6-benzylaminecarbonyl · 4- (3-chloro-aniline) -7H-pyrrole [2,3-d] pyrimidine, Melting point (decomposition) 295 ° C, FAB-MS: (M + H) + = 378, this paper size applies Chinese National Standard (CNS) Λ4 specification (210X297 mm) (Please read the precautions on the back before filling this page )-Binding · Order -78- Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs A7 B7___ ί 明 (), chloro-aniline) -6- (N · [3-methyl-but-1-yl] -amine formamidine ) -7Η-pyrrolopyrene [2,3-d] pyrimidine (Reference Example 45), melting point: 304-306 ° C, FAB-MS: (M + H) + = 358, zb) 5- (aniline-methyl)-(3-chloro-aniline) -7H-pyrrolo [2,3-d] pyrimidine and V- t zc 5) (Aniline-methyl) bucket (3-chloro-aniline &gt; 6-methyl-7H-pyrrolo [2,3-d] pyrimidine. Examples 20a, 20d, 20e, 20f, 20g, 201 and 201 The 20m compound is preferably obtained by reducing the equivalent nitro compound with Raleigh nickel using a method similar to that in Example 18. Example 21: 6- (4-acetamidine-benzene) -4- (3- (Chloro-aniline) -7H-pyrrolidinium 2,3-pyrimidine (Reference Example 20Ϊ) Add 0.05 ml (0.56 mmol) of acetic anhydride to 0.2 g (0.56 mmol) of 6 ^ (4-amine-benzene) 4- (3-Chloro-aniline) 7H-pyrrolo [2,3-d] pyrimidine was suspended in 0.5 ml of pyridine, and the reaction mixture was stirred at 0 ° C for 1 hour until TLC showed No starting material remained. The reaction mixture was poured into 50 ml of ice water, and the precipitate was filtered off and washed with hexane. The crude product was chromatographed on a silica gel column. The title compound was crystallized from THF / ethyl acetate / hexane; melting point> 310 ° C; MS: (M) + = 377. Example 22: The following compounds were prepared using a method similar to that of Example 1 or other examples of macros: a) 4- (3-chloro-aniline) -6- (4-propanamidin-benzene) 7H-pyrrolo [2,3-d] pyrimidine (prepared by a method similar to that in Example 21); melting point> 300 ° C; MS: (M) + = 391, b) 4- (3-chloro-aniline ) -6- (3-Propanamide-benzeneHH-pyrrolo [2,3-d] pyrimidine (prepared by a method similar to that in Example 21); melting point &gt; 300 ° C; MS: (M) + = 391, This paper size applies the Chinese National Standard (CNS) Λ4 specification (2 丨 OX 297 mm) II Binding «~ n (Please read the precautions on the back before filling this page) 472057 A7 B7 Employees of the Central Standards Bureau of the Ministry of Economic Affairs Printed by the cooperative V. Description of the invention () c) (R) -6- (4-Ethylamine-benzene M-K1-benzene-ethyl) · amine] -7H-pyrrolo [2,3-d] pyrimidine ( Prepared by a method similar to Example 21); Melting point: 304-305 ° C; MS: (M) + = 37 d) (R) -4-[(l-benzene-ethyl) -amine] -6- (4-Propanamide-benzene) -7H-pyrrolo [2,3-d] pyrimidine (prepared by a method similar to that in Example 21); MS: (M) + = 385 (refer to Example 28a) and e ) (R) 4- (3-Acetylamine-benzene - B) - amine] -7H- Bing-pyrrolo [2,3-d] pyrimidine; melting point: 150- 180 ° C; MS: (M) + = 371. Example 23: 4- (3-Chloro-aniline) -6- (4-isobutylamidine-benzene K7H-pyrrole, 2,3-dl pyrimidine at 0 ° C, 0.2 g (0.56 mmol) 6 · (4-amine-benzene) + (3-chloro-aniline) -7H-pyrrolo [2,3-d] pyrimidine and 0.064 ml (0.62 mmol) of isobutyric acid chloride and 1 ml of absolute dimethyl Acetamide was stirred for 2 hours until thin layer chromatography showed no starting material remaining. The reaction mixture was poured into 20 ml of ice water to precipitate the product. The product was washed with about 50 ml of ethyl acetate, about 2 ml of THF and Extract 20 ml of 5% NaHC03 aqueous solution. Wash the organic phase with water, dry, evaporate and concentrate to crystallize the desired compound. Filter the precipitate and rinse with cold ethyl acetate. Add hexane to the mother liquor to get more Many title compounds; melting point> 300 ° C; MS: (M) + = 405. Example 24: The following compounds were prepared by a method similar to that of Example 23: a) 4- (3 · chloro- Aniline> 6- (4-trimethylacetamido-benzene) -7H-pyrrolo [2,3-d] pyrimidine; melting point> 300 ° C; MS: (M) + = 419, b) 4 -(3-chloro-aniline) -6- [4- (DL-2_methyl-butylammoniumamine) -benzene] -7H-pyrrolo [2,3- d] pyrimidine; melting point> 300 ° C; FAB-MS: (M + H) + = 420, (Please read the notes on the back _ 4. Then fill in. Packing —: write this page) Applicable to Chinese National Standard (CNS) Λ4 specification (2 丨 〇 &lt; 297 mm) 472057 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention () c) 4- (3-Chloro-aniline ) -6- (4-Isoamylamine-benzene) -7H-pyrrolo [2,3-d] pyrimidine; melting point &gt; 300 ° C; MS: (M + H) + = 419, and d) 4 -(3-chloro-aniline) -6- (3-isobutylamidamine-benzene) -7H-pyrrolo [2,3-d] pyrimidine; melting point> 300 ° C; MS: (M + H) + = 405. Example 25: 4- (3-Chloro-aniline) -6- (4-ethylamine-benzene) -7H-pyrrole, 2,3-dl pyrimidine at 5 ° C, 110 microliters (1.93 mmol) ) Aldehyde was added with 0.3 g (0.89 mmol) of 6- (4-amine-benzene) · 4- (3-chloro-aniline) -7H-pyrrolo [2,3_d] pyrimidine and dissolved in 15 ml of THF. The reaction mixture was stirred at 5 ° C for 24 hours (organic solution). Then 75 mg (U5 mmol) of sodium cyanoborohydride was added. The reaction solution was stirred at room temperature for another 5 hours, and then concentrated by evaporation in the air. The residue was dissolved in ethyl acetate and adjusted to pH 2 with 1NHC1. The ethyl acetate phase was washed with water, dried and concentrated by evaporation. The crude product was chromatographed on a silica gel column. The title compound was crystallized from methanol / hexane or ethyl acetate / hexane; melting point: 265-270 ° C; MS: (M) + = 363. Example 26: The following compounds were prepared by a method similar to Example 25

Mf. · Preparation. A) (R) -6 &gt; (4-Diethylamine-benzene) winter [(1-benzene-ethyl) _amine] -7H-pyrrolo [2,3-d] pyrimidine; melting point: 286-287 ° C; MS: (M) + = 386, b) 4- (3-chloro-aniline) -6- (4-dimethylamine-benzene) -7H-pyrrole [2,3-d] Pyrimidine; Melting point: 279 -282 ° C; MS: (M) + = 363 (at 6- (4-amine-benzene) -4- (3-chloro-aniline V7H-pyrrole [2,3-d] pyrimidine Formed during the reaction with formaldehyde), c) 4- (3-chloro-aniline) -6- (3-ethylamine-benzene) -7H-pyrrolo [2,3-d] pyrimidine; MS: (M) + = 363 and d) 6- (4-Dimethylamine-benzene) -4-[(1-benzene-ethyl) -amine] -7H-pyrrolo [2,3-d] pyrimidine. This paper size applies to China National Standard (CNS) Λ4 specification (210X 297 mm) — ^^ 1 'nn mt ml flm Km ml * mt n ^ in ^ — im m 1 In * tin nw fmm in (Please read first Note on the back, please fill out this page again) -81-472057 A7 B7 Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention The reduction of the nitro compound produces the following compounds: a) 6- (4-amine-benzene) -4- (3-methyl-benzylamine) -7H-pyrrolo [2,3-d] pyrimidine, melting point: 291 -293 ° C; FAB-MS: (M + H) + = 330 &gt; b) (R) -6- (3-amine-benzene) · 4-[(1-benzene-ethyl) -amine] _7Η- Β is more steep than amorphous [2,3-d], amorphous, FAB-MS: (M + H) + = 330, c) (Min S) -6- (4-amine-benzene)> 4- [(l- (3-Chloro-benzene) -ethyl) -amine] -7H-pyrrolo [2,3-d] pyrimidine, melting point: 281-283. (:; FAB-MS: (M + H) + = 364. Example 28: The following compounds were prepared using a method similar to that in Example 2a) (R) -4-[(l-benzene-ethylamine] -6- (4-propanamine- Benzene) -7H-pyrrolo [2,3-d] pyrimidine; MS: (M) + = 385 (Reference Example 22d), b) (R &gt; 4-[(1-Benzene-ethyl) -amine]- 6 ^ (3-Propanamine-benzene) 7H-pyrrolo [2,3-d] pyrimidine; MS: (M) + = 385, iguana pan Qiao __ The following compounds are similar to those used in Example 23 Preparation: a) (R &gt; 6- (3-Isobutyramine benzene) ~ 4-[(1-phenylethyl) -amine] -7Η · pyrrolo [2,3-d] pyrimidine, melting point: 206- 208〇C; FAB-MS: (M + H) + = 400, b) (R &gt; 6 ~ (4 · isobutylamidine-phenylbenzene-ethyl) · amine] -7H-pyrrolo [2,3_d] Pyrimidine, melting point: 296-297 ° C; FAB-MS: (M + H) + = 400, c) (R &gt; 6- (4-trimethylacetamido-benzene) · 4 · [(1- Benzene-ethyl) -amine K7H-pyrrolidinium [2,34-pyrimidine, melting point> 300 ° C; FAB-MS: (M + H) + = 414 and d) (R) -H3-trimethylacetamidine Amine-benzene) ice [(1-benzene-ethylamine HH_D than pyrrolidine [2,3-d] pyridine, melting point: 148-152 ° C; FAB-MS: (M + H) + = 414. (Please read the notes on the back _ d • Items before filling —: Write this page) The size of the paper used in this edition applies to the Chinese national standard (CNS &gt; Λ4 specification (210X297) 漦 -82- 472057 A7 B7 V. Description of the invention () Example 30: 4- (3-Chloro-aniline) -6- (4-ethoxycarbonyl-benzene) -7H-pyrrole, 2,3-dl pyrimidine 900 mg (2.95 mmol) 4-chloro -6- (4-ethoxy-benzene) -7H-pyrrolo [2,3-d] pyrimidine and 0.63 ml (6 mmol) of 3-chloro-aniline and 22 ml of n-butanol were heated under reflux for 2.5 hours. The title compound was chromatographed on a silica gel column or crystallized from tetrahydrofuran / ether; melting point> 300 ° C; FAB-MS: (M + H) + two 393. The starting materials were prepared as follows: Step 30.1: 2- Amine-3-ethoxycarbonyl-5- (4-ethoxycarbonylbenzene) -1H-pyrrole Using a method similar to step 8.1, 4.92 g (29.5 mmol) of 2-methyl hydrochloride in 40 ml of absolute ethanol脒 · Ethyl acetate was reacted with 2.0 g (29.5 mmol) of sodium ethoxide and 4.0 g (14.8 mmol) of 2-bromo- (4-ethoxycarbonyl) -acetophenone to form the title compound; melting point: 150- 151 ° C; MS: (M) + = 302. Step 30 · 2: 6- (4-ethoxycarbonyl-benzene) · 7Η-pyridine幷 P, 3-dlpyrimidin 4-ol. Using a method similar to step 8.2, at 150 ° C and a protective gas, 2.6 g (8.6 mmol) of 2-amine-3-ethoxycarbonyl-5- (4 -Ethoxycarbonyl-benzene) -1H-pyrrole was heated overnight with 19 ml of formamidine, 8 ml of DMF and 0.6 ml of formic acid. Subsequent treatment using a method similar to step 8.2 yielded the title compound; melting point> 250 ° C FAB-MS: (M + H) + = 284. Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs (please read the precautions on the back before filling this page) Step 30 · 3: 4-Chloro-6- (4 -Ethoxycarbonyl-benzene) -7H-pyrrole 幷 2,3-dlpyrimidine Using a method similar to step 8.3, under a protective gas, 1.45 g of 6 ^ (4-ethoxycarbonyl · benzene) -7H- A solution of pyrrolidine [2,3-d] pyrimidine · 4 · alcohol in 15 ml of phosphorus oxychloride was heated for 2 hours and then processed to produce the title compound. Melting point: 250 ° C (decomposition); TLC-Rf = 0.63 (ethyl acetate / hexane [1: 1]); FAB-MS: (M + H) + = 302 ° This paper size applies to China National Standard (CNS) A4 (210X 297 mm) -83- 472057 A7 B7 V. Description of the invention () Example 31: 4- (3-chloro-aniline) -6- (3-Ethoxycarbonylbenzene) -7-pyrimidine 幷 2,3-dlpyrimidine The title compound was prepared by a method similar to that in Example 30; melting point &gt; 300 ° C; TLC-Rf = 0.66 (ethyl acetate Ester / hexane [1: 1]); FAB-MS: (M + H) + = 393. The starting materials were prepared as follows: Step 31.1. 2-Amine-3-ethoxyquin-5- (3-ethoxy curtain-benzene) -1H-B ratio The title compound was prepared by a method similar to step 30.1; Melting point: 136-137 ° C; TLC-Rf = 0.37 (ethyl acetate / hexane p: l]); MS: (M) + = 302. Step 31.2: 6- (3-ethoxycarbonyl-benzene) -7H-pyrrole, 2,3-dlpyrimidin-4-ol The title compound was prepared by a method similar to step 30.2; melting point> 250 ° C; TLC-Rf = 0.29 (ethyl acetate / hexane [1: 1]); FAB-MS: (M + H) + = 284. Step 31.3: 4-Chloro-6- (3-ethoxycarbonyl-benzene) -7H-pyrrole, 2,3-dl pyrimidine The title compound was prepared using a method similar to step 30.3; melting point> 250 ° C; TLC-Rf = 0_62 (ethyl acetate / hexane [1: 1]); FAB-MS ... (M + H) + = 302. Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs (please read the notes on the back before filling this page) Example 32: 4- (3-Chloro-aniline) -6- (4-qin-benzene) -7H-pyrrole幷 2,3-dl pyrimidine (see Example 20y) 0.2 g (0 :: 51 mmol) of 4- (3-chloro-aniline) -6- (4-ethoxycarbonyl-benzene) -7H-pyrrole幷 [2,3-d] pyrimidine (dissolved in 1.2 ml absolute ethanol) and 62.7 mg (1.52 mmol) of lithium hydroxide (dissolved in 1 ml of water) are heated under reflux until thin layer chromatography shows all the The raw material has disappeared (I2 hours). The solution was cooled to room temperature and adjusted to pH 2 with INNaOH solution, and the desired paper size was precipitated. Applicable to China National Standard (CNS) Λ4 specifications (210, X 297 mm) -84- 472057 A7 Central Ministry of Economic Standards Printed by the employee consumer cooperative f B7___ 5. Description of the invention () The product is filtered out. The title compound was recrystallized from ethanol / water or THF / hexane; melting point: &gt; 300 ° C; Rf = 0.47 (ethyl acetate / methanol [1: 1]), FAB-MS: (M + H) + = 365. Example 33: 4- (3-Chloro-aniline V6- (3-carboxy-benzene) -7Η · this ketone 幷 2.34 The title pyrimidine compound was prepared by a method similar to that in Example 32; melting point: &gt; 300 ° C; Rr = 0.5 (ethyl acetate / methanol [60:40]); FAB-MS: (M + H) + = 365 ° Example 34: 4 · (3 · Chloro-aniline &gt; 6 ~ ( 4-methoxycarbonyl-benzylpyrene 丨 2,3-dlpyrimidine 0.5 g (I.37 mmol) 4 ~ (3-chloro-aniline &gt; 6- (4-carboxy · benzene) -7H-pyrrole [2,3-d] pyrimidine was suspended in 100 ml of methanol suspension and 0,1 ml of concentrated sulfuric acid and heated under reflux for 24 hours. The solution was concentrated and stirred in methanol / ether. The crystals were filtered off and then suspended in methanol / Water. The suspension was adjusted to pH 7-8 with sodium bicarbonate solution and stirred at room temperature for 30 minutes. The crystals were filtered off with suction filtration, washed with water, methanol and ether and dried to obtain colorless crystals. Title compound; melting point:> 300 ° C; TLC-Rf = 0.6 (toluene / ethyl acetate [3: 7]); FAB-MS: (M + H) + = 378. Example 35: The following chemical The contents were prepared by a method similar to that of Example 34: a) 4 &lt; 3-chloro-aniline &gt; 6- (4-ethoxycarbonylbenzene) -7H-pyrrolidine [2,3-d] Pyridine; melting point> 300 ° C; FAB-MS: (M + H) + = 393 »b) 4- (3-chloro-aniline &gt; 6 · (4-propoxycarbonyl-benzene) -7H_pyrrole [2,3-d] pyrimidine; melting point &gt; 250 ° C; Rf = 0.41 (ethyl acetate / hexane [1: 1]); FAB-MS: (M + H) + = 407 'This paper size applies China National Standard (CNS) A4 specification (210X 297 gong) (Please read the precautions on the back before filling out this page)-Packing. Order -f -85- Duty printing by the Central Bureau of Standards of the Ministry of Economy Staff Printing 472057 A7 B7 V. Description of the invention () c) 4 ~ (3-chloro-aniline &gt; 6- (4-isopropoxycarbonyl-benzene) -7H-pyrrolo [2,3-d] pyrimidine; melting point> 250 ° C Rf = 0.41 (ethyl acetate / hexane [1: 1]); FAB-MS: (M + H) + = 407 and d) 4- (3-chloro-aniline) -6- (4-isobutyl Oxycarbonyl-benzene) -7H-pyrrolo [2,3-d] pyrimidine; melting point> 250 ° C; Rf = 0.48 (ethyl acetate / hexane [1: 1]); FAB-MS: (M + H) + = 42. Example 36: 4- (3-Chloro-aniline> 6- (4-dimethylamine-chizyl-2-phenylpyrrolidine) 2,3-dl pyrimidine at room temperature, 369 mg (1.01 Mmol) phenyl chloride · aniline p-, 3-d] pyrimidine, 0.4 ml (2.3 mmol) dimethylamine and 0.3 ml (1.51 mmol) DEPC (Ald rich company) dissolved in 10 ml of DMF and stirred for 1 hour. The brown suspension was diluted with water and filtered, and the crystals were washed with water, methanol and diethyl ether to give the title compound as colorless crystals; mp &gt; 250 ° C; FAB-MS: (M + H) + = 392. Example 37: 4- (3 · fluorene-aniline V6- (4-diethylamine curtain-benzene) -7H-pyrrole 幷, 2,3-dl pyrimidine The title compound was prepared by a method similar to Example 8; Melting point: &gt; 250 ° C; FAB-MS: (M + H) + = 420 = The following compounds were prepared by a method similar to Example 25: a) 4- (3-chloro-aniline) _6_ (3 _Dimethylamine-benzene) _7H-pyrrolo [2,3-d] pyrimidine; melting point: 282-284 C ί MS: (M) + = 363 ° Example 39: (RWW4 · ^ -benzene &gt; 4 -丨 (1-Benzene-ethyl amine 1-7H-pyrrole) The title compound in the form of a 2.3-dl pyrimidine colorless powder was prepared by a method similar to that of Example 10 '(R) -6- (4 · methoxy- Benzene &gt; 4-[(1-benzene-ethyl) -amine] _7Η · pyrrolopyrene [2,3-d] pyrimidine The paper size in this paper applies the Chinese National Standard (CNS) Λ4 specification (210X297 mm) --- ------ Install ----- ^ --.---- (Please read the notes on the back before filling in this education) -86- 472057 A7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs R7 * *-_ 5. Description of the invention () The methyl group is removed by boron dibromide; melting point: 216-218 ° C; FAB-MS: (M + H) + = 331. The starting materials are prepared as follows ... See step 39J : Lithium benzene) bucket 丨(1_Benzene-ethyl) _amine 7H_Pyrrolidine fZ3_d1 The title pyrimidine compound was synthesized by a method similar to that of Example 8 or 9 to 4_chlorodong (4 ~ methoxy-benzene) _7H in n-butanol. -Pyrrolidine [2,3-d] pyrimidine and (RH +)-l-benzene-ethylamine as starting materials; melting point: 256-257 ° C; FAB-MS: (M + H) + = 345 Example Example: _4- (3-Chloro-aniline) · 5 · dimethylamine methyl-6- (4-hydroxy-benzene V7H-pyrrole) 2.3-dl The pyrimidine title compound was prepared by the method of Example 3, Taking 4- (3-chloro-aniline &gt; 6- (4-meta-benzene) -7Η · 0-pyrrolo [2,3-d] pyrimidine and iodized N, N-dimethyl-methyleneimine as Prepared from starting materials; melting point: 243-244 ° C, MS: (M) + = 393. Example 41: 4 · (3-Chloro-aniline V6-ethoxycarbonyl-7H · pyrrolidine "2,3 ~ dl Pyrimidine Under argon pressure and 100 ° C, 29.0 (128 mmol) 4-chloro-6-ethoxychloride 7H_pyrrole [2,3, pyrimidine and 18.0 ml (171 mmol) 3- A solution of chloroaniline in 430 ml of n-butanol was stirred for 3 hours (almost after 1 hour, and then a concentrated suspension was formed). The reaction mixture was cooled to "50 ° C, then 400 ml of isopropanol / hexane Alkanes (1: 1) were added thereto. The reaction mixture was then cooled to room temperature, and the product was filtered off and washed with isopropanol and hexane. Stirring in diethyl ether gave the title compound: W-NMR (DMSOO 13.0 and 10.53 (2sb, 2HN), 8.48 (s, 1H), 8.13 (m, 1H), 7.78 (dm, J = 8, 1H), 7.76 ( s, 1H), 7.45 (t, J = 8, 1H), 7.21 (dm, J = 8, 1H), 4.37 (q, J = 7, 2H), 1.37 (t, J = 7, 3H). The starting materials are prepared as follows: The paper's dimensions are applicable to the Chinese National Standard (CNS) A4 specification (2 丨 0x297 mm) (please read the notes on the back Φ—-then fill in. Packing-: write this page) Order 472057 A7 B7 V. Description of the invention (4) Step 41.1: 2-amine-3,5-bis (ethoxyhexyl MH-pyrrole) at 0-5 ° C, 56.0 g (0.43 mmol) of 2 · formamidine-acetic acid Ethyl ester [see preparation method: LiebigsAnn. Cliem., 156l (l981)] was added to 172 ml of DMPU. 56.0 ml (0.45 mmol) of ethyl bromopyruvate was added dropwise within 30 minutes, and then at 60 ° C Next, the reaction mixture was heated for 3 hours. The dark brown reaction solution was poured into 1 liter of ice water, and extracted with 1 liter of ethyl acetate and twice with 0.5 liter of ethyl acetate. The organic phase was washed with 0.5 liter of water and 0.5 liter of brine. Washed three times, dried (Na2S04) and concentrated by evaporation. Column chromatography (Si02, hexane / ethyl acetate [1 ·· 1]) and crystallization from ether / hexane to give the title compound; melting point: 147-149 ° C; MS: (M) + = 226 Step 41.2: 6-ethoxycarbonyl · 4mai · 7Η-pyrrole 幷 2,3-dlpyrimidine, 51.5 grams of U27 mmol, 2-amine-3,5-bis (except air and 140 ° C) Ethoxycarbonyl MH · pyrrole, 455 ml of formamidine, 227 ml of DMF and 113 ml of formic acid were stirred for 27 hours. The yellow suspension formed was cooled to 0-5 ° C. It was filtered and washed with isopropanol and hexane. Yielded the title compound; W-NMR (DMSO-de): 13-12 (2 HX), 7.99 and 7_11 (2s, 2H), 4.31 (q, J = 7, 2H), 1.32 (t J = 7, 3H) Step 41.3: 4-Amo-6-ethylargonyl-7H-pyrrole, 2 &gt; dlpyrimidine, 32.0 g (154 mmol) of 6-ethoxycarbonyl-7H- D-pyrrolidine [2,3-d] pyrimidine was suspended in 308 ml (338 mmol) of POC13 'and heated with stirring at 120 ° C, during which the solids dissolved. After stirring at 120 ° C for 3 hours, excess POCl3 was distilled off (65 ° C external temperature; I5 mbar). The residue was suspended in 50 ml of ice-cold toluene. Filter and wash with toluene to give the title compound; melting point: 219-221 ° C; 4- this paper CNS) A4 size (210X297 male (please read the precautions on the back first_installation. Please fill in too: write this page) Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs-88- Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 472057 A7 B7 V. Description of the Invention () NMR (DMSO-c ^): 8.77 and 7_24 (2s, 2H), 4.39 (q, J = 7, 2H), 1_36 (t, J = 7, 3H). Further products can be concentrated by evaporation of the filtrate and then stirred in ethyl acetate / water. Example 42: 6 · Carboxy-4- (3. Chloroaniline V7H-pyrrole 2 2,3-dl pyrimidine A solution of 25 mg (0.6 mmol) of Li0HH20 in 0.4 ml of H20 was added dropwise to 95 mg (0.30 mmol) of 4 · (3-chloro- Aniline) -6-ethoxycarbonyl-7H-pyrrolo [2,3-d] pyrimidine was dissolved in a suspension of 0.7 ml of methanol. The reaction mixture was boiled for 4.5 hours, then cooled in an ice bath, and 0.6 ml of 1N HC1 solution was acidified. Filtered and washed with water to give the title compound; HPLC: tRet (Grad20) = 8.7; FAB-MS: (M + H) + = 289. Example 43: 6- (N-n-butyl-amine formamidine) -4- (3-chloro-aniline V7H-pyrrole 幷 2,3-dlpyrimidine at 60 ° C, 95 mg (0.30 mmol) 4K3-chloro-aniline &gt;; 6-Ethoxycarbonyl-7H-pyrrolidin [2,3-d] pyrimidine dissolved in 1 ml of n-butylamine and heated for 20 hours. The light yellow solution was evaporated and concentrated, and the residue was stirred with isopropanol and filtered. , And washed with hexane to give the title compound; melting point: 282 -284. (:; TLC-Rf = 0.45 (CH2C12 / methanol 10: 1); FAB-MS: (M + H) + = 344. Example 44 : 6-benzylamine carbonyl · 4 ~ (3-chloro-aniline V7H-pyrrole 幷 2,3-dlpyrimidine at 100 ° C, 95 mg (0.30 mmol) 4- (3-chloro-aniline) -6 · ethoxytten-7IW was heated for 27 hours with pyrridine [2,3-d] pyrimidine and 0.5 ml of benzylamine. The reaction mixture was cooled in ice water, stirred with 1 ml of isopropanol and 1 ml of hexane, and filtered. And drying to give the title compound; FAB-MS: (M + H) + = 378. Example 45: 4- (3-Chloro-aniline) -6-ΓΝ- (3-methyl-but-1-yl Vamine Formamidine 1-7H-Hbh slightly 幷 2,3-dl pyrimidine (Reference Example 20za) This paper size applies to Chinese National Standard (CNS) Λ4 specification (210X 297 cm) (Please read the back first Please pay attention to this page and fill in this page again.) T-, τ-89-472057 A7 B7 Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention () At 80 ° C, 95 mg (0.30 mmol) A solution of 4- (3-chloro-aniline) -6-ethoxy curtain-7H · pyrrolo [2,3-d] pyrimidine in 1 ml of (3-methyl-but-1-yl) -amine was heated for 12 hours . The reaction mixture was concentrated by evaporation, the residue was dissolved in THF, concentrated by evaporation again, stirred with ether and filtered to give the title compound; melting point: 304-306. . ; FAB-MS: (M + H) + = 358. Example 46: 4- (3-Chloro-aniline) -6_ (N, N-dimethyl-amine formamidine) -7H-pyrrole, 2,3-dl pyrimidine under nitrogen pressure, 97.6 mg (0.338 Mmol) 6-carboxy-4- (3-chloro · aniline) -7H-pyrrolo [2,3_d] pyrimidine was added to 7 ml of DMF, and 119 mg (0.40 mmol) of TPTU and one 164 mg (33 % In ethanol; 1.2 mmol) of dimethylamine in 1 ml of DMF was added to it. After 2 hours, another 30 mg TPTU was added to the reaction solution, and then stirred at room temperature for 2 days, then poured into 30 ml of ice water, stirred, filtered, and washed with water to give the title compound; HPLC: tRet ( Grad2G): 9.5; TLC-Rf = 0.38 (CH2C12 / methanol [10: 1]); FAB-MS: (M + H) + = 316. Example 47: 6-aminocarbonyl · 4- (3-chloro-aniline) -7H-pyrrolidinium 2,3-dl pyrimidine in a hot press at 120 ° C, 90 mg (0.285 mmol) ) 4- (3-Chloroaniline) -6-ethoxycarbonyl-7H-pyrrolo [2,3-d] pyrimidine was dissolved in 30 ml of methanol and a solution of 5 g of ammonia and heated for 48 hours. Silicone was added to the reaction mixture, which was then concentrated by evaporation, added to a silica gel column as a powder, and finally eluted with dichloromethane / methanol / THF (210: 35: 10). Filtration with methanol through an alumina column (basic) and stirring in ethyl acetate gave the title compound; HPLC: tRet (Grad2.): 8.1; TLC-Rf = 0 · 18 (CH2C12 / methanol [10: 1]); High-resolution MS: (M + H) + = 288.0669 (calculated 値 = 288.0652). (Please read the note on the back first '

Mm, • Refill the items * Pack —: Write this page) *-j__ 丁-'° _ The size of the paper is applicable to the Chinese National Standard (CNS) Λ4 specification (210X297 mm) -90- 7 5 20 7 Ministry of Economic Affairs A7 printed by the Consumer Standards Cooperative of the Central Bureau of Standards _______B7__ V. Description of the Invention () The title compound can be prepared by other methods as follows: 2.165 g (7.5 mmol) 6-Jun 4- (3-chloro-aniline) -7 private pyrrole [2,3- (1] pyrimidine (Reference Example 42) was dissolved in a mixture of 60 ml of THF and 10 ml of DMPU under reflux for 30 minutes, and then cooled to a fine suspension). Then, 824 µl (7.5 mmol) of N-morpholine was added dropwise, followed by 981 µl (7.5 mmol) of a solution of isobutyl chloroformate in 30 ml of thf. After 1 hour at 0 ° C, 824 µl of N-methylmorpholine and 981 µl of isobutyl chloroformate were added. The mixture was stirred for 1 hour, and then 70 ml of a saturated solution of NH3 in dioxane was added dropwise. After 3 hours, the mixture was concentrated in the air. The residue was poured into water, and the precipitate was filtered and washed with water and boiling isopropanol to give the title compound. More products can be isolated from the isopropanol filtrate. Example 48: 4- (3-Chloro-aniline) -6-methylaminecarbonyl-7H-pyrrole, 2,3 ~ dl pyrimidine in a bomb tube, at 50 ° C, 95 mg (0.30 mmol) ) 4- (3-Chloro-aniline) &gt; 6.Ethoxycarbonyl-7H-pyrrolidine [2,3 &gt; d] pyrimidine was dissolved in 6 ml of methylamine (33% in ethanol) and heated for 96 hours. The reaction mixture was evaporated Concentrated. Preparative HPLC was performed and stirred in diethyl ether to give the title compound; HPLC: tRet (Grad2.) = 8.6; TLC-Rf = 0,49 (CH2C12 / THF / ethanol [6: 2: 1]); FAB -MS: (M + H) + = 302 = Example 49: 4- (3-Chloro-aniline) -6-hydroxymethyl-7H-pyrrole, 2,3-dl pyrimidine under nitrogen pressure, 1.4 g (37 mmol) Lithium aluminum hydride was added in portions of 5.70 g (18 mmol) of 4- (3-chloro-aniline) -6-ethoxycarbonyl-7H-U. Pyridine [2,3-d] pyrimidine was dissolved in 300 ml of THF solution. After stirring at 50 ° C for 2 hours, 100 ml of water was added dropwise to the reaction mixture, and then it was passed through Serry plastic. This paper is sized according to Chinese National Standard (CNS) A4 (210X297). Li) (Please read the notes on the back before filling in this page)

-、 1T 472057 Consumers' Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs, India and India A7 B7 V. Description of Invention () (Celite) Filter. Water was added to the filtrate, which was then extracted three times with ethyl acetate. The organic phase was washed three times with water and brine. Dry (Na2S04) and concentrate by evaporation. Recrystallization from isopropanol gave the title compound; HPLC: tRet (Grad2 ()) = 8.2; TLC-Rf = 0.11 (CH2C12 / methanol [10: 1]); MS: (M) + = 274. Example 50: 4- (3-Chloro-aniline) -6-formamidine-7H-pyrrole, 2,3-dl pyrimidine Under ice cooling, 1.9 g of manganese dioxide (85%) was added to a 715 mg ( 2.6 mmol) 4- (3-Chloro-aniline) -6-methyl-7H-pyrrolo [2,3-d] pyrimidine was dissolved in 170 ml of a dichloromethane suspension, and at room temperature, The reaction mixture was stirred for 20 hours. 20 ml of DMPU was then added to the reaction mixture, which was stirred for 1 hour, and then filtered through Hyflo. The filter residue was stirred again in 50 ml of dichloromethane / DMPU (1: 1) and filtered again. The two filtrates were combined, concentrated by evaporation, and dissolved in ethyl acetate / THF and water. The aqueous phase was extracted twice with ethyl acetate, and the organic phase was washed four times with water and brine, dried (Na2S04), and concentrated by evaporation to a remaining volume of = 20 ml. Diethyl ether was added and filtered to give the title compound; HPLC: tRet (Grad2.): 10.1; TLC-Rf = 0.24 (CH2C12 / methanol). Example 51: (R) -6-ethoxycarbonyl ~ 4_ 丨 1-benzene-ethylamine 1-7H-pyrrole 幷 2,3-dl pyrimidine Under nitrogen pressure, 902 mg (4.0 mmol) 4 -Chloro-6-ethoxycarbonyl-7H · pyrrolo [2,3-d] pyrimidine (step 41.3) and 1.12 ml (8.8 mmol) of 1 (R) -benzene-ethylamine in 10 ml of n-butanol The solution was stirred at 150 ° C for 17 hours (dissolved initially and then formed a concentrated suspension). The reaction mixture was cooled, and the title compound was filtered off and washed with isopropanol and hexane; HPLC: tRet (Grad20) = 10.6; TLC-Rf = 0.49 (CH2C12 / methanol [10: 1]); FAB-MS : (M + H) + = 311 ° This paper size is applicable to the Chinese National Standard (CNS) Λ4 specification (210X 297 issued) --------- Installation -----— Order — ^ --- -(Please read the notes on the back before filling this page) -92- 472057 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention () Example 52: (R) -6-methylamine carbonyl ~ 4 -丨 1-Benzene-Ethylamine 1-7H-Pyridine 幷 2,3-dl pyrimidine In a bomb tube, 155 mg (0.50 mmol) 6-ethoxy curtain-4- [l (R)- Phenyl-ethylamine] -7H-pyrrolo [2,3-d] pyrimidine and 2.5 mg (0.05 mmol) of NaCN dissolved in 4 ml of methylamine (33% in ethanol) heated at 50 ° C 30 hours. The reaction mixture was dissolved in THF, 25 ml of water was added thereto, and the residue was concentrated by evaporation to a remaining volume of 25 ml. The formed crystals were filtered off and washed with water. Recrystallization from hot THF and ethyl acetate gave the title compound; HPLC: tRet (Grad2〇) = 8.3; TLORf = 0.31 (CH2C12 / methanol [10: 1]); FAB-MS: (M + H) + = 296. Example 53: The following compounds were prepared using a method similar to that described herein: a) (R) -6-Aminopyridine [1-phenyl-ethylamine] -7H-pyrrole [2,3-d ] Pyrimidine, b) (R) -6-cyanobenzene-ethylamine] -7H-pyrrolo [2,3-d] pyrimidine [made from compound a) above], c) 4- (3-chloro- Aniline &gt; 6-cyano-7H-pyrrolo [2,3-d] pyrimidine [can be prepared from the compound described in Example 47; Reference Example 54], d) (R) -6-formamidine [ 1-benzene-ethylamine] -7H-pyrrolidin [2,3-d] pyrimidine, e) (R) -6-aminetoluene · ethylamine] -7H-pyrrolidin [2,3-d] pyrimidine [available The above compound d) is obtained by reductive amination], f) 6 · aminomethyl · 4 · (3-gas · aniline) -7H-pyrrolo [2,3-d] pyrimidine [can be described in Example 50 Compound, obtained by reductive amination], g) 4- (3-Chloro-aniline) -6- (dimethylamine-methyl) · 7 吡 -pyrrole [2,3-d] pyrimidine, h) 6- (di Methylamine A) -4- [1 (foot) _benzene-ethylamine] -7H-Pyridoxine [2,3-d] pyrimidine, i) 6- (hexahydropyridine-A) -4- [l (R) · Benzene-Ethylamine] -7H-B than Pyridine [2,3-d] pyrimidine, and (Please read the notes on the back _ I # • Fill in the items. Pack — write this page) Paper scale suitable for China Standard (CNS) Λ4 (210X 297 mm) -93-472057 Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs A7 B7 V. Description of the invention () j) 4K3-chloro-aniline) (hexahydropyridine) ) -7H-B is slightly better than [2,3-d] pyrimidine. : 4- (3-Chloro-aniline V6-cyano-7H-pyrrole) 2,3-dl pyrimidine (Reference Example 53c) at 1.048 g (3.6 mmol) of 6-aminocarbonyl · 4 · (3-chloro- Aniline) -7H-pyrrolo [2,3-d] pyrimidine (Reference Example 47) and 0.7 ml of N, N-dimethyl-acetamidamine, 13 ml of phosphorus oxychloride was added. Stir at room temperature] After 4 hours and stirring at 100 ° C for 4 hours, the reaction mixture was poured into an ice-cold saturated solution of NaHC03. Extracted with ethyl acetate (three times), and the organic layer was washed with a saturated solution of NaHC03, water, and brine 'and dried ( Na2S04) and concentrated to form a solid. Column chromatography (along 02; ethyl acetate) was performed, and the crude product was stirred in ether and hexane to give the title compound; melting point: 284-287 ° C; TLC- Rf = 0.71 (CH2C12 / methanol [10: 1]); HPLC: tRet (Grad2 ()) = 11.8. Example 55: 4 · (3- 氡 -¾amine) · 6-methoxymethyl-7H-pyrrole [2,3-dl pyrimidine under argon at 85 mg (0.30 mmol) 4- (3-chloro · aniline> 6-hydroxymethyl-7H-pyrrolo [2,3-d] pyrimidine (reference Example 49) An ice-cold suspension in 5 ml of ether was added and 14 µl (0.15 mmol) of phosphorus tribromide was added. After stirring for 18 hours at 0 ° C and for 18 hours at room temperature (-4 ~ (3-chloro-aniline) -6-bromomethyl-7H-pyrrolo [2,3-d] pyrimidine), add 2 ml Methanol. The mixture was stirred for 2 hours, then 1 ml of sodium methoxide (5.4M in methanol) was added dropwise. After 18 hours, the mixture was concentrated in the air; the residue was redissolved in methanol, silicone was added, and the mixture was Evaporate to dry powder. Place this powder on top of a chromatography column (Si02; CH2C12 / ethanol [2: 1]). Elute with CH2C12 / ethanol [2: 1], concentrate, and use ethyl acetate / ether / Washed with hexane to get the title. The paper size of this paper applies Chinese National Standard (CNS) Λ4 specification (210X297 mm) (Please read the precautions on the back before filling this page)-Binding · Order 472057 A7 B7 V. Description of the invention () Compound; melting point: 226-230 ° C; TLC-Rf = 0.59 (CH2C12 / methanol [10: 1]); HPLC: tRet (Grad20) = 9.7. Example 56: 6- (N-Third-Butylamine醯 M- (3-Chloro-aniline V7H-lferole 幷 丨 2,3-dl pyrimide at 144 mg (0.50 mmol) 6-carboxol (3-chloro-aniline) · 7Η-pyrrole [2,3- d] pyrimidine (Reference Example 42) and 1 16 microliters (1.1 mmol) of tert-butylamine was dissolved in 5 ml of DMF solution, and 114 microliters (0.75 mmol) of diethyl cyanophosphonate (Aldrich; Milwaukee / USA) was added. After 4 hours, the reaction mixture was poured into ice water, stirred for 30 minutes, and finally filtered. The residue was redissolved in isopropanol, treated with charcoal and filtered. Concentrated in the air and washed with dichloromethane / ether to produce the title compound; HPLCtUGradyz 11'4; FAB-MS: (M + H) + = 344 〇 Printed by the Consumer Cooperative of the Central Bureau of Standards, Ministry of Economic Affairs (please first Read the notes on the reverse side and fill in this page) Example 57: 4- (3-Chloro-aniline) ~ 6 ~ (NN-dimethylamine-methyl) ~ 7Η · 1Ι 比 幷 幷 2,3-dl pyrimidine in At 50 ° C, 109 mg (0.40 mmol) of 4- (3-chloro-aniline) -6-formamidine-7H-larridine [2,3-d] pyrimidine (Reference Example 50), 110 micrograms A mixture of 1 liter (0.8 mmol) of dimethylamine (33% in ethanol) and 50 µl (0.88 mmol) of acetic acid in 6 ml of methanol and 1 ml of DMPU were shaken for 1 hour. Then》 20 mg of Raleigh nickel was added and the mixture was hydrogenated at 50 ° C. The catalyst was filtered off, washed with methanol, and the filtrate was concentrated. The residue was dissolved in ethyl acetate and a saturated solution of NaHC03, the aqueous phase was separated, and extracted twice with ethyl acetate. The organic phase was washed with water (twice) and brine, dried (MgS04), and concentrated in the air. Flash chromatography (Si02; CH2C12 / methanol [10: 148: 1]) was performed to obtain the title compound; several &lt;: -1 ^ = 0.06 (012 (: 12 / methanol [10.1]); HPLC: tRet (Grad2 ()) = 7.2. This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) '-95- 472057 Printed by A7 B7, Consumer Cooperatives, Central Standards Bureau, Ministry of Economic Affairs 5. Description of the invention () Example 58 : 5,000 dry capsules (each containing 0.25 g of the compound of formula 提到 mentioned in the previous example as the active ingredient) are prepared as follows: Composition of active ingredient 1250 g talc 180 g wheat starch 120 g magnesium stearate 80 grams of lactose and 20 grams of preparation method: the above material is crushed and forced through a 0.6 mm mesh size sieve. Using a capsule filling machine, 0.33 grams of the mixture is filled into gelatin capsules. Example 59: Soft capsule 5000 Gelatin capsules (each containing 0.05 g of the compound of formula (I) mentioned in the previous examples as the active ingredient) are prepared as follows: Composition of 250 g of propylene glycol laurate 2 liters (Lauroglycol) Preparation method: effective Ingredient Crush Suspend in Lauroglycol® (propylene glycol laurate, Gattefoss6 SA, Saint Priest, France) and grind in a wet grinder to a particle size of approximately 1 to 3 microns. Then use a capsule filler to dissolve 0.419 parts by weight The mixture is filled into soft gelatin capsules. Example 60: Soft capsules The paper size is applicable to Chinese national standards (匚! ^ 8) / \ 4 specifications (2 丨 0 乂 297 mm) --------- pack — (Please read the precautions on the back before filling this page), 1T-.ΦΦ. -96- 472057 A7 B7 V. Description of the invention () 5000 soft capsules (each containing 0.05 g of one mentioned in the previous examples) The compound of formula (I) is an active ingredient) is prepared as follows: Composition of 250 g of polyethylene glycol 400 1 liter (PEG 400)

Tween 80 1 liter preparation method: The active ingredient is crushed and suspended in PEG400 (polyethylene glycol with a molecular weight (Mr) of about 380 to about 420, Fluka, Switzerland) and Tween® 80 (polyoxyethylene sorbitan) Monolaurate, Atlas Chem. Ind. Inc., USA, supplied by Fluka, Switzerland) and ground in a wet grinder to a particle size of approximately 1 to 3 microns. A gelatin capsule filling machine was then used to fill the soft gelatin capsules in 0.43 g portions. ^^ 1 'n ^ ii I m · nn nn 1 ^ 1 111 (Please read the notes on the back before filling out this page) 1. The paper printed by the Central Consumers ’Bureau of the Ministry of Economic Affairs, the Consumer Cooperatives, is printed in accordance with Chinese national standards ( CNS) Λ4 specification (210X297 mm) -97-

472057 Revised Supplementary Specification to Patent Application No. 85108440 (July 88) Example of Biological Activity of Compounds of Formula I as Exemplified in Examples EGF-R ICD EGFR-ELISA BALB / MK ICs 0 [μΜ] IC50 0 [μΜ] IC5〇 [ μM) 1 0.007 0.015 0.16 2 0.007 0.015 0.16 5A 0.007 0.04 0.20 6 0.04 0.01 0.27 11 0.009 0.6 0.429 12 0.003 0.0015 0.54 16 0.029 0.6 0.62 17 0.14 ntnt 18 0.003 0.01 0.15 19 0.001 0.01 0.23 20d 0.002 0.01 0.26 2〇g 0.002 0.01 nt 20j 0.005 0.0004 0.13 201 0.003 0.01 &lt; 0.1 20m 0.004 0.02 0.31 20η 0.007 0.02 0.19 20ο 0.004 0.003 &lt; 0.1 20r 0.009 0.01 0.14 21 0.005 0.0004 0.13 22a 0.007 0.003 0.17 22b 0.005 0.003 0.28 22c 0.004 0.0001 0.34 22e 0.002 0.02 0.33 23 0.016 0.0015 0.38 24d 0.04 0.8 0.52 26b 0.006 0.01 0.12 27b 0.001 0.0002 0.19i 28a 0.006 0.02 0.15

28b 0.008 0.1 0.17 29a 0.019 0.06 0.4 29b 0.019 0.06 0.33 29d 0.034 0.08 0.65 36 0.016 0.003 n.t. 38a 0.016 0.06 0.25 39 0.001 0.002 0.44 47 0.002 0.8 0.96 48 0.003 0.1 0.58 472057 n-t

Claims (1)

4/2057 Chinese c 08440 patent application, please amend the patent scope (90 car 7 EI, A8 B8 C8 rvo defeat 7. i? 4 year old 1 £] * .: 〆, λ · * * &gt;. '1 »ν ..«-]; ·-··-.. ·-VI. Application scope 1 _ A 7Η-pyrrolo [2,3-d] pyrimidine derivative of the formula (I) or a salt thereof, ⑺ ' The Consumer Standards Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs, where q is 0 or 1, η is 1 to 3 (when q is 0), or η is 0 to 3 (when q is 1), and R is halogen or C "C7 alkyl, a) Ri and R_2 are each independently 〇 0 by amine formamidine-methoxy 'carboxy-methoxy group, oxocarbonyl-methoxy group, Cl-C7 alkyloxycarbonyl-methoxy group, Phenyl, amine, Cl-c7 alkylamino, c "(: 7-amino, N, N-di-CVC7 alkylamino, hydroxyl, carboxyl, CVC7 oxocarbonyl, carbamate 'N, N_di-(^-(^ alkane-aminomethyl or nitro-substituted phenyl; 10,000) hydrogen 'but 1 ^ and 112 cannot be hydrogen at the same time; r) unsubstituted pyridyl; 5) NT- Pyridin-2-yl, fluorenyl, cyano, carboxyl, ("C7 alkoxycarbonyl, carbamoyl, N-Q-C7 alkane-carbamoyl, N, N-di-CrC7 alkane-amine Formamyl, benzyl-aminoformamyl, formamyl, crC7 alkyl; or ε) substituted heart-heart alkyl, the substituents are: amine, Ci-C7 alkyl, light or Ci-C · / oxyl, or the standard of this paper (Chinese National Standards (CNS) 8.4) (210X297 mm) (Please read the precautions on the back before filling in this ) Order 472057 Printed by the Consumers 'Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs A8 B8 C8 D8 Patent application scope b) When q is 0' R, and one of the r2 bases is unsubstituted crc7 垸 base or unsubstituted dumb And the other of R | and r2 has one of the meanings specified in a) above (except hydrogen), or c) when q is 1, each of x and r2 is unsubstituted CrC? Alkyl Or unsubstituted phenyl 'or one of the meanings specified in a) above, and R6 is hydrogen, C'C7 alkyl or alkoxycarbonyl', but in Formula I η is 0, q is 1, 1 ^ and Rule 6 is hydrogen, and compounds except R2 are methyl. 2 · As the compound of formula (I) or a salt thereof in item 1 of the patent application scope, wherein q is 0 or 1, and η is 1 to 3 (when q 0), or n is 0 to 3 (when q is 1), R is a halogen or a CrC · / alkyl group, a)! ^ Is hydrogen and R2 is a methylamine-methoxy, carboxy- Methoxy, oxycarbonyl-methoxy 'CrC7 alkoxycarbonyl-methoxy-, phenyl, amine, alkylamino, (^-(: 7 alkylamino, N, N-di-CrC7 Alkylamino, hydroxyl, carboxyl, CrC7 alkoxycarbonyl, carbamoyl, N, N-di-C "C7 -Carbamoyl or nitro-substituted phenyl; unsubstituted pyridyl; N-benzyl-pyridin-2-yl; fluorenyl; cyano; carboxyl; C "C7 alkoxycarbonyl; carbamate N-CVC7alkyl-aminomethylamino; N, N-di-C 丨 -fluorenylmethyl-aminomethylamino; N-benzyl-aminomethylamino; methylamido; CrC? Alkylamino, or C "C7 alkyl" substituted by Cr C7 alkoxy, or b) when q is 0, one of: ^ and! ^ Is unsubstituted C1-C ·; alkyl or unsubstituted benzene Base, and the other of R, and R2 bases has one of the meanings specified in a) above (except for hydrogen), or the paper size applies to China National Standard (CNS) A4 (210X 297 mm) ) (Please read the notes on the back before filling out this page), 1T φ ·. 472057 Consumer cooperation of the Central Sample China Bureau of the Ministry of Economic Affairs 衽 Printed A8 B8 C8 _____ D8 VI. Application for patent scope C) When q is I 'h Is hydrogen and R2 is unsubstituted phenyl, and R 6 is nitrogen or C1-C7 pit group. 3 _ The compound of formula (I) or a salt thereof according to item 1 of the scope of the patent application, wherein q is 1, η is 0 to 3, R is halogen or cardio-cardioalkyl, a) each of cardio and ruler 2 is carbamidine -Methoxy, quinone, methoxy, methoxy, q-C7 alkoxycarbonyl-methoxy, phenyl, amine, CrC7 alkylamino, CrC7; feamino, N, N-di-CrC7 amine, ceryl, aryl, (: "(: 7 alkoxycarbonyl, carbamoyl, n, N-di-C" C7 alkane-amine fluorene or nitro substituted Phenyl 'is hydrogen (but Ri and R2 cannot be hydrogen at the same time), unsubstituted pyridyl, N-fluorenyl-pyridine-2 -yl, thethyl, cyano, phenyl, CrC &quot; , Carbamoyl 'N_crC7-carbamoyl, N, N-di-C, C7 aminomethyl, N-methylaminomethyl, methylmethyl, Ci-c: 7 alkyl, Or crC7 alkyl substituted with amine, di_Ci_C7 alkylamino, or C7C7 alkoxy, or b) R, and R_2 are each unsubstituted Ci_c? Alkyl or unsubstituted Phenyl 'or any of the meanings specified in a) above, and h is hydrogen, (: "(: 7 alkyl or C" C7 alkoxycarbonyl, but η in formula I is 0, q 1 ′ and 1 ′ are each hydrogen, except for compounds which are &amp; methyl. 4. The compound of formula (1) or a salt thereof according to item 丨 of the patent application range, wherein q is 0 and η is 1 to 3, yA4 ^ (21〇x297 ^) ---- (Please read the precautions on the back before filling in this book) Contest · • I-1 ^ 1 I— I II 472057 ABCD Employees ’Cooperative Consumption Cooperation Du printed 6. The scope of patent application R is halogen or Q-Ct alkyl, a) R ^ R2 are each phenyl, amine, C | -C? Alkyl amine, C1-C7 amine, N, N-di-C | -C7 alkylamino, hydroxy, carboxyl, Ci_C7 carbonox, carbamoyl, N, N-di-c 1 _ 垸 7 垸 -carbamoyl or terminal substitution The phenyl group is hydrogen (but 1 ^ and 2 must not be hydrogen at the same time), unsubstituted pyridyl, N-fluorenyl-pyridine-2 -yl, phenyl, cyano, phenyl, Ci-C7 Oxycarbonyl'aminomethyl, N-C1-C7fluorenyl-carbamoyl, N, N-di-C1-C7alkane-carbamyl, formamyl, c! -C7alkylfluorenyl, or Ci-C7 alkyl substituted with amine, di-C ^ Ct alkylamino, hydroxyl or Crc7 alkoxy, or b) one of R! And R2 is unsubstituted Q-Cy Group or unsubstituted phenyl group, and the other one of the ^ groups has the meaning specified in a) above (apart from hydrogen) 5 · As a compound of formula 丨Or a pharmaceutically acceptable salt thereof, wherein q is 0 or 1, η is 1 or 2 (when q is 0), or !! is 0 to 2 (when q is 1), and R is halogen or (^ -(: 7 alkyl group, and a) Ri is hydrogen or unsubstituted or CrCy alkyl group substituted with di-dC? Alkylamino group and R2 is carbamoylmethoxy, carboxymethoxy, fluorene Oxycarbonylmethoxy, C ^ C: 7 alkoxycarbonylmethoxy, CrC7 alkoxycarbonyl, carboxyl, N, N-di-C rC7 alkyl-amine formamyl, phenyl, amine, c7 Amino group, di-(^-(^ alkylamino group, (^-(: 7 alkylamino group, hydroxy or nitro substituted phenyl group, hydroxy_C | _C7 alkyl, amine_C | _C7 alkyl 、 C_ π laaniasara qoc'il ^ n '—___ ^ This paper uses the Chinese National Standard (CNS) Eighty-fourth Secret (―210 &gt; &lt; 297 mm 丨) (Please read the precautions on the back before reading Fill in this note) Order 472057 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A8 B8 C8 D8 Scope of patent application: C7 alkylamine-crC7 alkyl group, methylamino group, cyano group, carboxyl group, oxocarbonyl group, aminomethylamino group, N_C | _C7 alkyl_aminomethylamidino group, NN · diC C7 alkyl-aminomethane , Pyridyl, N_benzylaminocarbamyl, N_benzylpyridinium 2-yl or fluorenyl, or b) when q is 1, R1 and r2 are each a methyl group, and R6 is hydrogen ' Methyl or C 丨 _c7 alkoxycarbonyl. 6. The compound of formula (1) or a pharmaceutically acceptable salt thereof according to item 1 of the scope of patent application, wherein q is 0 or 1, π is 1 or 2 (when q is 0), or η is 0 to 2 (when q is 1), R is halogen or (^-(: 7 alkyl), and K is hydrogen or unsubstituted or substituted with di-Ci-C: 7 alkylamino group , And R2 is a carbamoylmethoxy group, a carboxymethoxy group, a oxocarboxymethoxy group, a CrG alkoxycarbonylmethoxy group, an alkoxycarbonyl group, a carboxyl group, and N, N_di-C 丨 -O alkyl group. · Carbamoyl, phenyl, amino, ^-(^ alkylamino, di-q-C7 alkylamino, Cl_C7 alkylamino, hydroxy or nitro substituted phenyl, and I is hydrogen, Methyl 'or C ^ -Ct alkoxycarbonyl group. 7. The compound of formula (I) or a salt thereof as claimed in item i of the patent application scope, wherein q is 0 or 1, and η is 1 or 2 (when q is 0), or η is 0 to 2 (when q is 1), R is halogen, and a) R! is hydrogen or unsubstituted or C | -C7 amine group C | -C7 Side-by-side use (CNS) A4 now (210X297 mm) (Please read the notes on the back before filling in this I) Order 472057 A8 B8 C8 D8 Patent application alkyl group, and r2 is carbamoylmethoxy, carboxymethoxy, benzyloxycarbonylmethoxy, methoxycarbonylmethoxy, ethoxycarbonyl, carboxyl, phenyl, amine, Ethylamino, hydroxy or nitro substituted phenyl is carboxy, ethoxycarbonyl, N- (VC7 alkyl-aminomethylamidino, eridinyl, N-benzyl-pyridin-2-yl or fluorenyl, Or b) when q is 1, 1 ^ and 112 are each a methyl group, and R6 is hydrogen, methyl, or methoxycarbonyl. 8. The compound of the formula (I) or the pharmacologically acceptable compound as claimed in item 1 of the patent application range. Accepted salts, which are selected from the group consisting of 4-(3-Ga-aniline) -6-(pyridin-2-yl) -7H-pyrrolo [2,3-d] pyrimidine, 4-(3-Ga-aniline) -6-(pyridine-2 -yl) -7H-pyrrolo [2,3-d] pyrimidine hydrochloride, 4-(3-gas-aniline) -5 -dimethylamine methyl-6-(pyridine-2 -Yl) -7H-pyrrolo [2,3-d] 11 bite,-4-(3-chloro-4 -fluoro-aniline) -6-(pyridin-2-yl) -7H-pyrrolo [2 , 3-d] pyrimidine, printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs (please read the precautions on the back before filling out this page) 4- (3 -Ga-Dongamine) -5 -A-6-(^ 7 Thanodo-2-yl) -7H- Than 11 each of [2,3-d] pyrimidines, 4-(3-chloroaniline) -5 -methyl-6-(N-benzyl-pyridine-2 -yl) -7H-pyrrolo [2,3- dp dense lake bromide, 4-(3-chloro-4 -fluoro-aniline) -5 -methyl-6-(pyridin-2-yl) -7H-pyrrolo [2,3-d] η dense bite, 4 -(3 -Ga-aniline) -6-(biphenyl-4 -yl) -7H-pyrrolo [2,3-d] pyrimidine, 4-(3 -Ga-aniline) -6-(Tea-2- Base) -7H-pyrrolo [2,3-d] pyrimidine, Q \ 56 \ 5fiSSB ΠΠΓΛΙ AN Good paper size applies Chinese National Standard (CNS) A4 specification (210.X 297 mm) 472057 ABCD Printed by Employee Consumer Cooperatives 6. Scope of Patent Application 4-(3 -Ga-aniline) -6-(2 -Hydroxy-benzene) -7H-pyrrolo [2,3-d] pyrimidine, 4-(3 -chloro- Aniline) -6- (3-hydroxy-benzene) -7H-pyrrolo [2,3-d] pyrimidine, 4- (3-chloro-aniline) -6- (4-hydroxy-benzene) -7H-pyrrolo [2,3-d] pyrimidine, 4- (3-chloro-aniline) -5-dimethylamine methyl-6- (4-hydroxy-benzene) -7H-pyrrolo [2,3-d] σ shout , 4-(3 -chloro-aniline) -5 -dimethylaminemethyl-6 -benzene-7fluorene-pyrrolo [2,3-d] pyrimidine, 4-(3 -gas-aniline) -5 -methyl- 6-(4- Hydroxy-benzene) -7H-pyrrolo [2,3-d] pyrimole, 4-(3-gas-aniline) -6-(4-nitro-benzene) -7H-pyrrolo [2,3-d] Pyrimidine, 4- (3-Ga-aniline) -6- (4-amine-benzene) -7H-pyrrolo [2,3-d] pyrimidine and 4-(3-Ga-aniline) -9H-pyrrolo [3 ', 2 \ 4,5] pyrrolo [2,3-d] pyrimidine, and pharmaceutically acceptable acid addition salts thereof. 9. The compound of formula (I) or a pharmaceutically acceptable salt thereof according to item 1 of the scope of the patent application, which is selected from a) benzylamine-5,6-dimethyl-7H-pyrrolo [2,3-d ] Pyrimidine, b) (R)-5,6 -dimethyl-4-[(1 -benzene-ethyl) -amine] -7H-pyrrolo [2,3-d] pyrimidine, c) (S)- 5,6 -dimethyl-4-[(1 -benzene-ethyl) -amine] -7H-pyrrolo [2,3-d] pyrimidine, d) (R)-6-(4-amine-benzene) -4-[(1 -Benzene-ethyl) -amine] -7H-pyrrolo [2,3-d] 11 bite, e) (S)-6- (4-amine-Ben) -4-[( I-private-B) -amine] -7H-leaf sigma each [2,3-d]. Secret disease, _Ο \ 56 \ 56556 DOCVLAN_ &quot; 7 -_ This paper size is applicable to China National Standard (CNS) A4 specification (210X297 mm) (Please read the precautions on the back before filling this page). Patent scope f) 6-(4-amine-benzene) -4-T amine-7H-pyrrolo [2,3-d] pyrimidine, g) 6-(4-amine-benzene) -4-[(3- Gas- 芊) -amine] -7H-pyrrolo [2,3-d] Mouth tight, h) (R)-6-(4-amine-benzene) -4-[(1 -methoxycarbonyl-fluorene ) -Amine] -7H-pyrrolo [2,3-d] shout, 1) (S)-6-(4-amine-benzene) -4-[(1-methoxycarbonyl-benzyl) -amine] -7H-pyrrolo [2,3-d] σ dense bite, j) 6-(4 -acetamido-benzene) -4-(3 -gas-aniline) -7Η-pyrrolo [2,3-d] Pyrimidine, k) 6-(4 -Aminemethylmethoxy-benzene) -4-(3 -Ga-aniline) -7H-pyrrolo [2,3-d] 11 dense bite, l) 6-(4- Amine-benzene) -4-(3 -methyl-aniline) -7H-pyrrolo [2,3-d] pyrimidine m) 6- (4-amine-benzyl) -4- (3 -murine-4-gas --Aniline) -7H-17 than 11 each of [2,3-d] σ dense bite, η) 6-(3 -acetamido-benzene) -4-(3 -gas-aniline) -7Η-pyrrole And [2,3-d] π dense bite, the central standard of the Ministry of Economic Affairs Printed by the Consumer Cooperatives of the Quasi-Bureau (Please read the precautions on the back before filling out this page) 〇) 6-(3-Amine-Benzene) -4-(3-Aminoaniline) -7Η-pyrrolo [2,3- d] pyrimidine, P) 6-(4 -carboxymethoxy-benzene) -4-(3 -gas-aniline) -7H-pyrrolo [2,3-d] pyrimidine, q) 6-(4-[ Oxocarbonyl-methoxy] -benzene) -4-(3-gas-aniline) -7H-pyrrolo [2,3-d] p, bite, r) 6-(3-aminoformamidine methoxy-benzene ) -4-(3 -Gas-aniline) -7H-pyrrolo η nnr \ i am-B-: Zhang scale is applicable to China National Standard (CNS) A4 specification (210X297 mm) 472057 ABICD VI. Scope of patent application [2 , 3-d] σ dense lake, s) 4-(3 -gas-aniline) -6-(4-methoxycarbonylmethoxy-benzene) -7Η-pyrrolo [2,3-d] σ dense lake, t) 4-(3-chloro-aniline) -6-(3-methoxycarbonylmethoxy-benzene) -7fluorene-pyrrolo [2,3-d]. Close bite, u) 6 -carboxy-4-(3 -gas-aniline) -7H-pyrrolo [2,3-d] pyrimidine, v) 4-(3 -chloro-aniline) -6 -ethoxycarbonyl- 7 H-pyrrolo [2,3-d] pyrimidine, w) 6-(N -n-butyl-amine formamidine) -4-(3 -gas-aniline) -7H-pyrrolo [2,3-d] σ dense bite, X) 4-(3 -gas-aniline) -6-(4 -ethoxycarbonyl-benzene) -7Η-pyrrolo [2,3-d] U dense bite, y) 6- (4- Carboxy-benzene) -4- (3-gas-aniline) -7H-pyrrolo [2,3-d] pyrimidine, z) 6-(N-benzyl-amine formamidine) -4-(3-gas-aniline ) -7H-pyrrolo [2,3-d] σ dense bite and za) 4- (3-Ga-aniline) -6- (N- [3-methyl-but-1-yl] -amine formamidine) -7Η-pyrrolo [2,3-d] pyrimidine and its pharmaceutically acceptable salts. Printed by the Consumers' Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs (please read the precautions on the back before completing this page) 10. If the compound of formula (I) or the pharmaceutically acceptable salt of item 1 of the scope of patent application, the Selected from a) 4-(3 -chloro-aniline) -6-(4 -propanamidin-benzene) -7H-pyrrolo [2,3-d] P dense lake, b) 4-(3 -gas- Aniline) -6-(3-propanamidin-benzene) -7H-pyrrolo [2,3-d] cr dense bite, c) (R)-6-(4-acetamidine-benzyl) -4- [(1 -Ben-B) -amine] -7H-pyrrolo-QiljgiiSSSSljOOGi.LAN -——---- * Q _------, Zhang scales are applicable to China National Standards (CNS) A4 (210X297) Mm) 472057 ABCD VI. Patent application scope [2,3-d] murmur, d) (R)-4-[(l-winter-ethyl) -amine] -6- (4-propanamine-ben ) -7H-17 than 11 each [2,3-d] η bite, e) (R)-6-(3 -acetamidine-benzene) -4-[(1 -benzene-ethyl) -amine ] -7Η-pyrrolo [2,3-d] dense lake, f) 4-(3 -gas-aniline) -6-(4 -isobutylamidamine-benzene) -7H-pyrrolo [2,3- d] p dense bit, g) 4-(3-chloro-aniline) -6-(4-trimethylacetamido-benzene) -7H-pyrrolo [2,3-d] ° h) 4-(3 -Ga-aniline) -6-[(4-(DL- 2 -methyl-butylamine) -benzene] -7H-17 Billo [2,3-d] shout bite, 1 ) 4-(3 -Gas-aniline) -6-(4 -isoamylamine-benzene) -7H-pyrrolo [2,3_d] σ dense bite, j) 4-(3 -chloro-aniline) -6 -(3 -Isobutylamine-benzene) -7Η-pyrrolo [2,3-d] n dense bite, k) 4-(3 -gas-aniline) -6-(4-ethylamine-benzene)- 7H-pyrrolo [2,3_d] pyrimosis' Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (Please read the precautions on the back before filling this page) l) 6-(4 -Ethylamine-benzene) -4 -[(1 -Benzene-ethyl) -amine] -7H-pyrrolo [2,3-d] Mouth'm) 4-(3 -Ga-aniline) -6-(4-dimethylamine-benzene ) -7H-pyrrolo [2,3-d] σ dense lake, η) 4-(3 -chloro-aniline) -6-(3 -ethylamine-benzene) -7Η-pyrrolo [2,3-d ] Pyrimidine and 〇) 6-(4 -dimethylamine-benzene) -4-[(丨 -benzene-ethyl) -amine] -7H-pyrrolo [2,3- Q \ 5m5eSS8 ΠΟΓ: \ Ι AN 10 -The size of the dagger is applicable to the Chinese National Standard (CNS) A4 (210X297 mm) 472057 ABCD 6. Scope of patent application d] σ dense bite and its pharmaceutically acceptable salt. 11. The compound of formula (I) or a pharmaceutically acceptable salt thereof according to item 1 of the scope of patent application, which is selected from 6- (4-amine-benzene) -4- (3-methyl-fluorene) -7Η- Pyrrolo [2,3-d] pyrimidine, (R) -6- (3-amine-benzene) -4-[(1-benzene-ethyl) -amine] -7H-pyrrolo [2,3-d] π dense bite, (R, S) -6- (4-amine-benzene) -4-[(1- (3-gas-benzene) -ethyl) -amine] -7H-pyrrolo [2,3-d ] Pyrimidine, (R) -4-[(l-benzene-ethyl) -amine] -6- (3-propanamine-benzene) -7H-pyrrolo [2,3-d] 11 )-6-(3 -isobutylamidamine-benzene) -4-[(1 -benzene-ethyl) -amine] -7H-pyrrolo [2,3-d] ° dense lake, (R) _ 6- (4 -Isobutyramine-benzene) -4-[(1-Benzene-ethyl) -amine] -7H-pyrrolo [2,3-d] = close bite, (R)-6-(4 -tri Methylacetamidine-benzene) -4-[(Benzene · ethyl) -amine] -7H-pyridine B [2,3-d] σ dense bite, (R)-6-(3 -Trimethyl Ethylamine-benzene) -4-[(Benzene-ethyl) -amine] -7 吡 -pyrrolo [2,3-d] pyrimidine, printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs (please read the back first) For the matters needing attention, fill in this page again) 4-(3 -Ga-aniline) -6-(3 -Ethoxycarbonyl-benzene) -7H-pyrrolo [2,3-d] pyrimidine Bite, 4-(3-Ga-aniline) -6-(3-Carbox-benzene) -7H-pyrrolo [2,3-d] pyrimidine, 4-(3-Ga-aniline) -6-(4- Methoxycarbonyl-benzene) -7H-pyrrolo [2,3-d] pyrimidine, 4-(3 -gas-aniline) -6-(4-propoxycarbonyl-benzene) -7H-pyrrolo [2, 3-d] Pyramid bite, -11-Wood paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) 472057 Printed by A8 B8 C8 D8 of Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 4-(3- Gas-aniline) -6-(4 -isopropoxycarbonyl-benzene) -7H-pyrrolo [2,3-d] P dense bite, 4-(3 -gas-aniline) -6-(4 -isobutyl Oxycarbonyl-benzene) -7H-pyrrolo [2,3-d] σ dense bite, 4-(3 -Ga-aniline) -6-(4-dimethylaminecarbonyl-benzene) -7H-pyrrolo [2 , 3-d] σ dense attack, 4-(3-chloro-aniline) -6-(4-diethylaminecarbonyl-benzene) -7Η · pyrrolo [2,3-d] tr dense lean, (R) -6-(4 -Diethylamine-benzene) -4-[(1 -Benzene-ethyl) amine] -7H-pyrrolo [2,3-d] α, 4-(3 -chloro-aniline) -6-(3 -Dimethylamine-benzene) -7H-pyrrolo [2,3-d] pyrimidine, 4-(3 -Ga-aniline) -5 -dimethylamine-6-(4-hydroxy- Benzene) -7H- Pyrano [2,3-d] ° Bite, 4-(3 -Ga-aniline) -6-(N, N -dimethyl-amine formamidine) -7H-pyrrolo [2,3-d] σ Dense lake, 6-aminocarbonyl-4-(3-gas-aniline) -7 pyrene-pyrrolo [2,3_d] pyrimidine, 4-(3-gas-aniline) -6-methylaminocarbonyl-7 pyrene-pyrrolo [2,3-d] pyrimidine, 4- (3-gas-aniline) -6-hydroxymethyl-7H-pyrrolo [2,3-d] pyrimidine, 4- (3-chloro-aniline) -6-methyl醯 -7H-pyrrolo [2,3-d] pyrimidine, (R) -6-ethoxycarbonyl-4-[1-phenyl-ethylamine] -7H-pyrrolo [2,3_d] pyrimidine, (R) -6 -methylamine carbonyl-4-[1 -benzene-ethylamine] -7H-pyrrolo [2,3-d] pyrimidine, (R)-6 -aminoformamidine-4-Π-benzene-ethylamine] -7H-pyrrolo [2,3-d] pyrimidine, (R) -6-cyano-4-[1-benzene-ethylamine] -7H-pyrrolo [2,3-d] pyrimidine, 4-(3 -Ga · aniline) -6-cyano-7H-pyrrolo [2,3-d] pyrimidine, (R) -6-formamidine 4- 4- [l-phenyl-ethylamine] -7H-leaf [2,3-d] σ dense bite, -19-This paper size is applicable to Chinese National Standard (CNS) A4 (2l0X 297 mm) (Please read the precautions on the back before filling this page) Ministry of Economic Affairs-Central Bureau of Standards Employees' Cooperative Cooperative Prints 0v ^ fivsesse nor. \ T an. This paper size is in accordance with China National Standards (CNS) A4 (2! 〇 × 297mm) A8 B8 C8 D8 Application Patent scope Amine-4- [Bien-ethylamine] -7H-pyrrolo [2,3_d] pyrimidine, 6-Amine-4-((3-gas-epiamine) -7H-11 than heparin [2 , 3-d] Cough bite, 4- (3-Gas-aniline) · 6 _ (dimethylamine-methyl) _ 7H_pyrrolo [2,3_d] ring, (R)-6 · (dimethylamine -A) _ 4-[1 -Benzene-ethylamine] -7H-pyrrolo [2 3_d] 4-(3 -Ga-aniline) -6 -methoxymethyl-7H-pyrrolo [2,3-d] Shout and bite, 6- (N · Third-butyl-amine formamidine) -4- (3-Gas-aniline) · 7Η "^ Hip [2,3-d] pyrimidine and 4-(3-chloro-aniline) -6-(N, N -dimethylamine-methyl) -7H-pyrolo [2 3_d] and its pharmaceutically acceptable salts. 12. For example, the compound of formula (I) or its pharmacy An acceptable salt, the compound is (R) -6- (4-hydroxy-phenyl-phenyl-ethylpyrimidyl] -7H-pyrrolo [2,3-d] pyrimidine. The compound of formula (1) or the pharmaceutically acceptable salt thereof in the item of Fanyuan! R) -4-[(f-benzene · ethyl) -amine] -6 · (3-propionamine-benzene) -7Η-pyrrolo [2,3-d] pyrimidine. 14 · —A kind of treatment for warming Blood animals include pharmaceutical compositions of human tumors, which contain a compound of formula (I) or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 13 of the scope of patent application for an effective antitumor dose, together with the same pharmaceutical carrier. 15. The compound of formula (I) or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 13 of the scope of patent application, which is a pharmaceutical composition for preparing a chemical treatment for tumors. The compound of formula (I) or a pharmaceutically acceptable salt thereof according to any one of items 1 to 13, which is used for the chemotherapy of tumors. 17. —7H-pyrrolo [2,3-d of formula (I)] ] Pyrimidine derivatives or their salts 13- {Please read the precautions on the back before filling this page) Order 472057 Scope of Patent Application (I) In the printed version of the Consumer Cooperatives of the Central Bureau of Economic Affairs, 0q is 0 or 1, n is 1 to 3 (when q is 0), or η is 0 to 3 (when q is 1) , R is a halogen or an alkyl group, a) Ri and R2 are each independently α) amine formamidine-methoxy, carboxy-methoxy, amidoxycarbonyl-methoxy, cv C7 alkoxycarbonyl-methoxy , Benzyl, amine, Ci_C7 alkylamino, C7 alkylamino, N, N-di-CVC7 alkylamino, hydroxyl, carboxyl, CVC7 oxyalkyl, carbamoyl, N, N-di- CrCy alkyl-carbamoyl or nitro-substituted phenyl; Lu) hydrogen, but Ri and I cannot be hydrogen at the same time; T) unsubstituted pyridyl; (?) N-benzyl-pyridin-2-yl , Fluorenyl, cyano, carboxyl, (^-(: 7 alkoxycarbonyl, carbamoyl, N-(^-(: 7 alkyl-aminomethyl), N, N -di-ci_c7 alkyl-amine methyl Fluorenyl, N-benzyl-aminoformyl, formamyl, CrC7 alkyl; or e) substituted Ci-C? Alkyl, the substituents are: amino, di-CrC? Alkylamino, or hydroxyl Or CrC · / alkoxy 'or b) when q is 0, one of Ri and R is unsubstituted Cl_C7 alkyl or unsubstituted phenyl', and the other of R! And R2 has At a) 〇 (Please read the precautions on the back before filling this page), 1T f. 〇nnr. \ LAN ^ Good paper size is applicable to national standards (CNS) A4 specifications (2 丨 〇 &gt; &lt; 297) C) A8 B8 C8 D8 has one of the meanings specified in the scope of patent application (other than hydrogen), or C) when q is 1, Ri and R2 are each unsubstituted CI_C? Alkyl or unsubstituted phenyl, Or has one of the meanings specified in a) above and R6 is argon, CrC7 alkyl, or Cl-c7 alkoxycarbonyl, but in Formula I, η is 0, q is i, and heart and ruler 6 are each hydrogen, and &amp; Except for methyl compounds, this method includes a) a pyrrolo [2,3-d] pyrimidine derivative of formula (Π) (please read the precautions on the back before filling this page) (Π) Order Printed by the Employee Consumer Cooperative of the Xinyang Sub-Bureau of the Ministry of Economic Affairs (J〇B 〇 〇0 &gt;} (In formula (II), X is a suitable leaving group, 芩 is hydrogen or 丨 -aryl ^-alkyl and the rest of the substituents are as defined above for the compound of formula ⑴. Any free functional group present in the 2 group is protected by an easily removable protecting group) reacted with an amine of formula (III), Η m (R, R6, η and q in formula (III) are as defined for the compound of formula ⑴ above, necessary When any free functional group present in the R group is easily removed, the protective paper is applied to the standard of the Chinese family standard (CNS) A4 (21 × 297 mm 472057 A8 B8 C8 D8. 6. Application for patent scope protection), And remove any existing protective groups and (when present) the Z group of the 1_aryl_Ci-CT alkyl group, or b) in the presence of a dehydrating agent and a third amine, ] Pyrimidine-4 -one derivatives (Please read the precautions on the back before filling out this page) (IV) (Z 'in formula (IV) is 1-aryl-Ci-C7 group' R! And R2 are as defined above for the compound of formula ⑴ 'if necessary, And any free functional group present in the R_2 group is protected by an easily removable protective group) reacted with more than one amine of the formula (III) and remove any existing protective groups, or printed by the Consumer Cooperative of Yinyang Standard Bureau of the Ministry of Economic Affairs ) When it is desired to prepare a compound of formula (I) in which the heart is dimethylamine-methyl and the remaining substituents are as defined for the compound of formula (I) above, a compound corresponding to formula (I) (wherein the heart is hydrogen And the rest of the substituents are as defined in the compound of formula (I) above, if necessary, the protecting group of any free functional group present in the R2 group and the protective group is easily removed) and N, N-dimethyl-methylene iodide Ammonium reaction 'and remove any protective groups present, or d) when it is desired to prepare at least one of the R, X and r2 groups is a phenyl substituted with a hydroxy group' and the remaining substituents are as defined in the formula ⑴ For compounds, a compound corresponding to the formula (at least one of R, And R2 group is phenyl substituted by methoxy group, and the remaining substituents are as defined in the compound of formula (I) above. When necessary, any free functional group present in R, Xin and &amp; groups is protected by easy removal. Base protector) and tribromide 0Λ56 \ 56556 DOC \ LAN 16 Private paper standards are applicable to China National Standards (CNS) A4 (2 丨 〇 X M7) 472057 ABCD VI. Application for patent scope boronization reaction 'and remove any Existing protecting group, or e) If it is desired to prepare at least one R, R1 and r2 group is a phenyl group substituted with an amine group, and the remaining substituents are as defined above for the compound of formula (I), the compound Corresponding to the compound of formula (I) (wherein at least one of the R, Ri and R2 groups is a phenyl group substituted with a nitro group, and the remaining substituents are as defined above for the compound of formula (I) 'if necessary' R, 1 and r2 Any free functional group present in the group is protected by a protective group that is easily removable), catalytic hydrogenation, and removal of any protective group present, and after the implementation of a method a) to e) 'if a salt needs to be prepared, it will be formed Free compounds of formula (I) are converted into salts or, if When preparing a free compound 'converted to salts of the compounds of formula (I) into a free form of the compound. 18. A compound according to any one of claims 1 to 13 of the scope of application for a patent, which is a preparation method of the method for application of scope 16 of the patent. 19_ A method for preparing 7H-pyrrolo 0,3-d] pyrimidine of formula (la) Derivatives or their salts (Please read the notes on the back before filling out this page) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (la) In the formula (la), η is 1 to 3, R is halogen or Ci-q alkyl, a) R | and R2 are each phenyl group, amine group, C1-C7, and amine group Ci-C7 ^ G'Sgg ^ COGOO.OOO'iLAM Table paper size: China National Standard (CNS) A4 Regulation (210X297 mm) ^ / ZUD / A8 B8 C8 D8 Patent Application C ^ -Ct alkylamino, hydroxy, carboxyl, CrC7 alkoxycarbonyl, carbamoyl, N, N-di-C r (: 7 alkane-carbamoyl or nitro substituted phenyl, is hydrogen ( But mind! ^ Cannot be hydrogen at the same time), unsubstituted 17-pyridinyl 'N-benzyl-pyridin-2-yl, fluorenyl, cyano, carboxyl, CV C7 oxocarbonyl, carbamate, ] ^-(: 1-0: 7 Alkyl-aminomethylamino, N, N-di-fluorenyl-coordinary-aminomethylamidino, methylamido, Q-Ct alkylamino, or amino -CrC? Alkylamino, hydroxy or CrC7 alkoxy substituted CrG alkyl, or b) one of the R & R2 groups is an unsubstituted fluorenyl alkyl or unsubstituted phenyl 'and The other of the heart and the heart base has one of the meanings specified in a) above (other than hydrogen), and the method includes a) derivatizing a pyrrolo [2,3-d] pyrimidine of formula (II) Thing (Π) (Please read the notes on the back and fill in this card first.) Seal of the Consumer Affairs Cooperative of the Central Bureau of the Ministry of Economic Affairs (X in formula (II) is the appropriate leaving group, z is hydrogen or 1-aryl -Ci-C7 alkyl and other substituents are as defined for the compound of formula (la) above, and if necessary, any free functional group present in the R2 group is protected by a protective group that can be easily removed) and an amine of formula (Ilia) Derivative reaction, (R). (Hla) «igCVCQGGG DOO ^ Li» iM paper size is applicable to China National Standard (CNS) A4 specification (210 × 297 mm) 472057 ABCD 々, R and η in the scope of patent application (Formula (丨 丨 丨 a) are as above Definition of compound of formula (丨 a), if necessary, 'any free functional group present in the R group is protected by an easily removable protective group)' and remove any protective group and (if present) 丨 _aryl_Ci_ C7 alkane Z group, or b) in the presence of a dehydrating agent and a third amine, a pyrrolo [2,3_d] p (Please read the precautions on the back before filling this page) (IV) 〇〇 £ \ (In formula (IV), Z 'is 1-aryl-C 丨 -c7 垸 yl' R 丨 and ruler 2 is as above formula (Ia ) The meaning of the compound, if necessary, any free functional groups present in the ^ and ^ 2 groups are protected by easy-to-remove protecting groups) and reacted with more than one aniline of the formula (III), and remove any existing protecting groups- , Or printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs C) Party 4 When preparing a compound of formula (la) in which the formula is monomethylamine-methyl and the remaining substituents are as defined above for the compound of formula (la), A compound corresponding to formula (la) (wherein the heart is hydrogen and the remaining substituents are as defined above for the compound of formula (la), if necessary, any free functional groups present in the heart and &amp; group are protected by easy removal Group protector) reacts with N, N_dimethyl_methyleneimmonium iodide 'and removes any protective groups present, or d) when it is desired to prepare at least one of the R, R and C 2 groups is benzene substituted by a hydroxyl group When the compound of formula (la) is as defined above and the remaining substituents are as defined for the compound of formula (la) above, Ia) compounds (at least one of the R and R_2 groups are phenyl groups substituted with methoxy .. and the rest are substituted for this paper. Dimensions ϋ 家家 准 (CNS) A4 * i4M 21GX297 public i ' ) -------- 472057 ab, cd The scope of the patent application is defined as the compound of formula (la) above, and if necessary, R, Rl, and any free functional group in the group can be easily protected by a protective group) React with tri / boron odorant 'and remove any protective groups present, or e) To prepare at least one of the R, X, and r2 groups is a radical substituted with an amine group, and the remaining substituents are as above formula ( Ia) Definition of a compound of formula (Ia) When a compound of formula (Ia) is equivalent to a compound of formula (Ia) (wherein at least one of the R, Ri and R2 groups is a phenyl group substituted by a nitro group, and the remaining substituents are as the above formula ( Ia) Definition of the compound. If necessary, any free functional groups present in the R '1 ^ and R2 groups are protected by a protective group that is easily removed) catalytic hydrogenation' and any protective groups present are removed, and a method a ) To e) after 'if a salt is to be prepared, the free compound of formula (la) is transformed into Or a salt, when preparing a free compound For 'salt of a compound of the formula Conversion (La) to be formed into the free compound. (Please read the notes on the back before filling out this page) Order Competition Ministry of Economic Affairs_Central Bureau of Standards Employees' Cooperatives Printed 20-wood paper is again applicable to China National Standard (CNS) Μ specifications (2 丨 OX 297)