TW587078B - 4,4-disubstituted-3,4-dihydro-2(1H)-quinazolinones useful as HIV reverse transcriptase inhibitors - Google Patents
4,4-disubstituted-3,4-dihydro-2(1H)-quinazolinones useful as HIV reverse transcriptase inhibitors Download PDFInfo
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- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/78—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 2
- C07D239/80—Oxygen atoms
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Abstract
Description
587078 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明(1 ) 發明範疇 本發明係關於可作爲逆轉錄酶抑制劑之4,4 -雙取代-3,4 -二氫-2(1氫)-喹唑啉酮,含此等物質之醫藥組合物及 診斷套組,利用此等物質治療病毒感染或作爲分析標準或 試劑之方法,及製備此等物質之中間物及歩驟。 發明背景 現已了解兩種不同類型的人類免疫不全病毒(型_1 HI V及 型-2 HI V)是造成後天免疫不全症(AIDS)的原因。雖然 HIV血清成陽性的個體初期時沒有症狀,但是罹患AIDS後 會發展AIDS相關的併發症(ARC),受感染個體的免疫力嚴 重受到抑制,因而導致個體身體衰弱,最後並造成致命的 機會性感染。 AIDS疾病導因於HIV-1或HIV-2病毒複雜的生活史,病 毒的生活史始於病毒鍵結至人類宿主T - 4淋巴球免疫細胞 上(其係病毒顆粒上保護外膜表面上之_蛋白與淋巴細胞上 之CD4醣蛋白鍵結),一旦鍵結後,病毒顆粒脱去醣蛋白 外膜,穿透過宿主細胞之細胞膜,並將其RN A去套膜。病 母顆粒之酵素----逆轉綠酶----會將RNA轉綠成單股 DNA ’其後病毒RNA被降解,進而產生第二股的DNA。 所產生的雙股DNA即可崁入人類細胞中的基因,而這些正 基因可作爲病毒複製之用。 此時,RNA聚合酶將崁入之DNA轉錄成病毒rna,而 病毒RNA再轉譯成gag-ροΐ融合醣蛋白之先驅物,其後 HIV蛋白酶再切除酷蛋白而產生成熟的病毒蛋白。因此, 本紙張尺度適用中國國家榡準(CNs ) A4規格(210X297公釐) (請先閱讀背面之注意事項再填寫本頁.) -· 、?τ 587078 Μ Β7 經濟部中央標準局員工消費合作社印製 五、發明説明(2 ) 蛋白切除流程中負責調節使病毒顆粒成熟而成爲具有感染 力病毒的是HIV蛋白酶。 由於病毒感染後殺死了免疫系統的T細胞,故主要备責 殺死入侵病毒顆粒之主要人類免疫系統的反應負荷很重, 除此(外’用於製造新病毒顆粒之病毒逆轉錄酶並不非常 專-性,因而常造成轉綠作用的錯誤,因而導致病毒保護 外膜表面上之醣蛋白不斷的在改變,逆轉錄酶專一性的缺 之降低了人體免疫性效率,因爲抗體是專一性針對某一醋 蛋白所產生的’而對另—種的醣蛋白是無效用0,因此可 用以對抗病毒抗體之數量減少,病毒持續的繁殖,而免疫 2逐漸的哀退,最後’ HIV完全控制人體的免疫系統, 在未投用抗病毒藥物,免疫調節物(或下 性感染死亡。 曰 二在已證明病毒生活史中至少有三個重要的時期是抗病 母樂物的標的:⑴病毒顆粒最初結合至τ_4淋巴細胞或 :嗜”田胞位置’(2)病毒RNA轉錄成病毒DNA(逆轉錄 酶,及⑴mv蛋白酶對gag_p〇1之切除作用。 οϊΓΛϊ個重要時期抑制病毒(即病毒rna轉錄成病毒 繁殖時驟)已提供現今許多治療AIDS之方法,病毒顆粒 RNA Φ M發生此種轉綠㈣,因爲病毒的基因編碼於 之藥I而宿主細胞祇能辨識舰,投與能阻斷逆轉錄酶 f物即可抑制病4 DNA形成,因而可終止ΗΠΜ的複 現今已發展出各種干擾病毒複製之化合物以治療A咖, I— n n n i-^又 m I d (請先閱讀背面之注意事項再填寫本頁)587078 A7 B7 printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (1) Field of the invention The present invention relates to 4,4-disubstituted-3,4-dihydro-2 (4) which can be used as a reverse transcriptase inhibitor. 1 Hydrogen) -quinazolinone, a pharmaceutical composition and a diagnostic kit containing these substances, a method of using these substances to treat a viral infection or as an analytical standard or reagent, and preparation of intermediates and steps of these substances. BACKGROUND OF THE INVENTION It is now known that two different types of human immunodeficiency virus (type-1 HI V and type-2 HI V) are responsible for acquired immune deficiency disease (AIDS). Although HIV-seropositive individuals have no symptoms at the beginning, they will develop AIDS-related complications (ARC) after suffering from AIDS, and the immune system of the infected individual will be severely suppressed, which will lead to physical weakness and eventually fatal opportunism. infection. AIDS is caused by the complex life history of the HIV-1 or HIV-2 virus. The life history of the virus begins when the virus binds to human host T-4 lymphocyte immune cells. _ Protein is bound to the CD4 glycoprotein on lymphocytes). Once bonded, the virus particles de-glyze the outer membrane of the glycoprotein, penetrate the cell membrane of the host cell, and envelop its RN A. The enzyme of the diseased mother particle-reverse green enzyme-will turn the RNA into green single-stranded DNA ’and then the viral RNA is degraded to generate a second strand of DNA. The resulting double-stranded DNA can be inserted into genes in human cells, and these positive genes can be used for virus replication. At this time, the RNA polymerase transcribes the incoming DNA into viral RNA, and the viral RNA is then translated into the precursor of the gag-ροΐ fusion glycoprotein, after which the HIV protease excises the cool protein to produce a mature viral protein. Therefore, this paper size is applicable to China National Standards (CNs) A4 (210X297 mm) (Please read the precautions on the back before filling out this page.)-·,? Τ 587078 Μ Β7 Staff Consumer Cooperatives, Central Standards Bureau, Ministry of Economic Affairs Printing 5. Description of the invention (2) HIV proteinase is responsible for regulating the maturation of virus particles to become infectious virus during protein removal process. Because the virus kills the T cells of the immune system after virus infection, the main human immune system is responsible for killing the invading virus particles. The reaction load is heavy. In addition (except for the virus reverse transcriptase used to make new virus particles and It is not very specific, which often causes the error of greening, which leads to the continuous change of glycoproteins on the surface of the protective membrane of the virus. The lack of specificity of reverse transcriptase reduces the immune efficiency of the human body because antibodies are specific. It is produced against one vinegar protein and is ineffective against another glycoprotein. Therefore, it can be used to reduce the number of anti-virus antibodies, the virus continues to reproduce, and the immune 2 gradually retreats. Finally, the HIV is completely To control the body's immune system, antiviral drugs, immune regulators (or inferior infections have died without administration.) At least three important periods in the life history of the virus have been proven to be the target of anti-disease: prions The particles initially bind to τ_4 lymphocytes or: "field cell sites" (2) transcription of viral RNA into viral DNA (reverse transcriptase, and ⑴mv protease excision of gag_p〇1 ΟϊΓΛϊ Inhibition of the virus (ie, viral RNA transcription into viral reproduction steps) in an important period has provided many of the current treatments for AIDS. The virus particle RNA Φ M has undergone such a greenish turn, because the virus's gene encodes the drug I. The host cell can only recognize the ship, and it can block the formation of disease 4 DNA by blocking the reverse transcriptase f. Therefore, it can stop the reversion of ΗΠΜ. Nowadays, various compounds that interfere with the replication of the virus have been developed to treat Aca, I- nnn i -^ 又 m I d (Please read the notes on the back before filling this page)
、1T 1 I- I -, 1T 1 I- I-
本紙張尺度適用中( CNS ) A4規格 587078 ΑΊ B7 五、發明説明(3 ) ’ 例如,核菩類似物,諸如3,_疊氮基_3、去氧胸嘧啶核甞 (AZT),2’,3’-二去氧胞嘧啶核苷(ddc),2,,3,_'二去氧胸嘧 哫核甞(d4T),2’,3,_二去氡肌甞(ddI),及2,,3,·二去氧- 3’-硫胞嘧啶核荅(3TC)等已證明在逆轉錄酶(rt)時期具有 阻滯HIV複製的效力。 、… 現在正積極發展非HIV逆轉錄酶抑制劑的研究,例‘, 現在已發現某些苯幷崎畊酮及4唑琳鲖可抑制HIV逆轉綠 酶’以預防或治療HIV的感染並可治療AIDS。 美國專利案5,519,021號揭示具下式苯幷$ p井酮之逆轉'綠 酶抑制劑: ‘ 衣-- (請先閲讀背面之注意事項再填寫本頁〕This paper is applicable in the standard (CNS) A4 specification 587078 ΑΊ B7 V. Description of the invention (3) 'For example, nuclear analogues such as 3, _azido_3, deoxythymidine nuclear pyrene (AZT), 2' , 3'-dideoxycytosine riboside (ddc), 2 ,, 3, _ 'dideoxythymidine ribosome (d4T), 2', 3, _dideoxymuscle (ddI), and 2,3, · dideoxy-3'-thiocytosine nuclear tritium (3TC) and others have been shown to have the effect of blocking HIV replication during the reverse transcriptase (rt) period. …… Now is actively developing research on non-HIV reverse transcriptase inhibitors, for example, 'It has now been found that certain benzophenazine and 4 oxalinam can inhibit HIV reverse green enzyme' to prevent or treat HIV infection and can Treatment of AIDS. U.S. Patent No. 5,519,021 reveals the reversal of 'benzylidene p pionone' green enzyme inhibitor with the following formula: ‘clothing-(Please read the precautions on the back before filling this page]
訂· 其中X是南素,Z爲氧。 、 歐洲專利案0,53〇,994號及w〇93/〇4〇47號揭示具式(A) 喹峻啉酮之HIV逆轉錄酶抑制劑:Order · where X is Nansu and Z is oxygen. , European Patent Nos. 0,53,994, and WO93 / 〇4〇47 disclose HIV reverse transcriptase inhibitors of the formula (A) quinazolinone:
587078 經濟部中央標準局員工消費合作社印製 Μ Β7 五、發明説明(4 ) ^ 其中G爲各式基團,R3及R4»爲氫,/爲氧,R2是未經 取代之烷基,未經取代之晞基,未經取代乏炔'基,未經取 代之環烷基,未經取代雜環基,及視情況爲經取代之芳香 基,而R1是各式的基團,包括經取代之燒基。 W〇95/l2583中亦揭示式A之HIV逆轉錄酶本p、制、劑,此 篇文獻中,G是各式的基團,r3及R4爲氫,z爲氧,、R2 是經取代之烯基或經取代之炔基,而R1是環烷基,炔基, 烯基,或氰基。WO 95/13 273中揭示WO 95/125,83中一種 化合物((S)-(_)-6_氣-4-環丙基_3,4-二氫·4((2·吡啶墓) 乙基)-2 (1氫)-喳唑淋酮)的非對稱性合成作用。 製備上述喹唑啉酮之合成步驟詳述於下列參考文獻中: 何比斯(Houpis)等人,Tetr.Lett.1994,35(37),6811-6814 ;特克(Tucker)等人,j· Med· Chem· 1994, 37, 2437-2444 :及何夫艾(Huffman)等人,J. Org. Chem· 1995,60, 1590-1594。 DE4,32〇,347專利案中説明具下式之嗓唑琳酮:587078 Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs Β7. V. Description of the Invention (4) ^ where G is various groups, R3 and R4 »are hydrogen, / is oxygen, and R2 is an unsubstituted alkyl group. Substituted fluorenyl, unsubstituted alkyne ', unsubstituted cycloalkyl, unsubstituted heterocyclyl, and optionally substituted aromatic, and R1 is a group of various formulas, including Substituted alkyl. W095 / l2583 also discloses the HIV reverse transcriptase p, preparation and agent of formula A. In this document, G is a group of various formulas, r3 and R4 are hydrogen, z is oxygen, and R2 is substituted Alkenyl or substituted alkynyl, and R1 is cycloalkyl, alkynyl, alkenyl, or cyano. WO 95/13 273 discloses a compound of WO 95 / 125,83 ((S)-(_)-6_gas-4-cyclopropyl_3,4-dihydro · 4 ((2 · pyridine tomb) Asymmetric synthesis of ethyl) -2 (1hydro) -oxazolone. The synthetic steps for preparing the above quinazolinone are detailed in the following references: Houpis et al., Tetr. Lett. 1994, 35 (37), 6811-6814; Tucker et al., J Med. Chem. 1994, 37, 2437-2444: and Huffman et al., J. Org. Chem. 1995, 60, 1590-1594. DE 4,32,347, describes a zomolone with the following formula:
其中R是苯基,碳環,或雜環。本發明不考慮此類的化合 物。 即使現今的逆轉錄酶抑制劑相當的成功,但仍發現m v 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) (請先閲讀背面之注意事項再填寫本頁)Where R is phenyl, carbocyclic, or heterocyclic. The present invention does not consider such compounds. Even today's reverse transcriptase inhibitors have been quite successful, but it is still found that the size of this paper applies to the Chinese National Standard (CNS) A4 specification (210X297 mm) (Please read the precautions on the back before filling this page)
587078 A7 經濟部中央標準局員工消費合作社印製587078 A7 Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs
J«/〇78 :H£ '發明説明(6J «/ 〇78: H £ 'Invention note (6
Crb 'ΚΛ〇 】中匕’二^3以8定義如後文,而其立體異構备形 J 、'形式<混合物,或其醫藥學上可接受之鹽 類均是有效之逆轉錄酶抑制劑。 實例之詳細説明 、 [1 ]因此’在第一個具體實例中,本發明提供一種式ϊ 的新穎化合物: (請先閱讀背面之注意事項再填寫本頁) -iti Γ R1 R2Crb 'ΚΛ〇] is defined as 8 below, and its stereoisomeric preparation J,' form < mixture, or its pharmaceutically acceptable salts are effective reverse transcriptases Inhibitor. Detailed description of the examples, [1] Therefore, in the first specific example, the present invention provides a novel compound of formula ϊ: (Please read the precautions on the back before filling this page) -iti Γ R1 R2
經濟部中央標準局員工消費合作社印製 或其立體異構物或醫藥學上可接受之鹽類,其中: R1是經1_7齒素取代之Cl-3烷基; R2是選自經1-2個R4取代之Cl_5烷基,經1-2個R4 取代之C 2 - 5晞基,及經1個R 4取代之C 2 _ 5炔基; R3(在每種情形下)是獨立選自於(^_4烷基,OH,Cb4 烷氧基,F,Cl,Br,I,,NR5R5a,N02,CN, C(0)R6,NHC(0)R7,及 NHC(0)NR5R5a,· 另一種情形是,假若存有2個R3基團,且附接鄰近碳原 -9 - 本紙張尺度適用中國國家標準(CNS ) A4規格(210 X 297公釐) 經濟部中央標準局員工消費合作社印製 587078 kl ____ B7_ 五、發明説明(7 ) --- 子,則可共同組成-0CH20-; R4選自經0·2個R3取代之(:3_5環烷基,經〇_5個R3取 代之苯基,及經0-2個R3取代之5-6員雜環系統(其 内含1 _ 3個選自氧,氮,及硫雜原子); R5及R5a是獨立選自氫及Cw烷基; R6選自氫,羥基,Cm烷基,Cm烷氧基,及 NR5R5a ; R7選自Cm烷基,及Cu烷氧基; R 8選自氫,C 3 · 5環燒基,及C 1 - 3燒基;及 η 選自 0,1,2,3,及4。 [2]在較佳的具體實例中,本發明提供一種式j之新穎化 合物,其中: R1是經1-7個鹵素取代之Cu烷基; R 2選自經1個R4取代之c i · 5院基,經1個R4取代之 C2-5晞基,及經1個R4取代之C2_5炔基; R3(在每種情形下)是獨立選自Cb4烷基,羥基,Cl_4 燒氧基,F,Cl,Br,I,NR5R5a,N02,CN, C(0)R6,NHC(0)R7,及 NHC(0)NR5R5a ; 另一種情形是,假若存有2個R3基團,且附接其鄰近碳 原子,則可共同組合成_ 〇CH20-; R4選自經0-2個R3取代之C3_5環烷基,經0-2個R3取 代之苯基,及經〇·;[個R3取代之5_6員雜環系統(其内含 1 - 3個選自氧,氮,及硫雜原子); R5及R5a獨立選自氫,CH3及C2H5 ; -10 - 本紙張尺度適用巾國國家標準(CNS) A4規格(210x297公釐) (請先閱讀背面之注意事項再填寫本頁) 訂 587078 經濟部中央標準局員工消費合作社印製 五、發明説明(8 R 選自氫,羥基,CH3,C2H5,ocu3,0CU3, OC2H5,及 NR5R5a ; R 選自 ch3,C2H5,OCH3,及 〇c2H5 : R8選自氳,環丙基,ch3及c2h5 ;及 n選自0,1,2,及3。 [3 ]在更佳的具體實例中,本發明提供一種式j的新穎化 合物,其中: R1 選自 cf3,及 c2f5 ; R選自經1個R4取代之c i _3虎基,經1個R4取代泛 C 2 - 3晞基,及經1個R 4取代之C 2 · 3块基; R3(在每種情形下)獨立選自Cb3烷基,羥基,Ci 3尸 氧基,F,Cl,Br,I,NR5R5a,N02,CN, C(0)R6,NHC(0)R7,及 NHC(0)NR5R5a : 另一種方式是,假若存有2個R3,且附接其鄭近 子,則可共同組成-0CH20-; 又·、 R4選自經0-2個R3取代之C3_5環烷基,經0-2個 取代之苯基,及經0 - 1個R3取代之5 - 6員雜環系会、 (其包括1 - 3個選自氧,氮,及硫雜原子): R5及R5a獨立選自氫,CH3及C2H5 ; R6 選自氫,羥基,CH3,C2H5,OCH3,〇c2i^ NR5R5a ,及 C请先聞讀背面之注意事項存填寫本頁) -· R7 選自 CH3,C2H5,OCH3,0〇2印 R8選自氫,CH3及C2H5 :及 n選自0,1,及2。 -11 - 本紙張尺度適用中國國家標準(CNS ) A4規格(210X 297公釐) 經濟部中央標準局員工消費合作社印製 587078 五、發明説明(9 ) [4]在更佳的具體實例中,本發明提供一種式I化合物, 其中: R1 是 CF3 ; R 2選自經1個R 4取代之c 1 · 3燒基,經1個r 4取代之 C2_3烯基,及經1個R4取代之C2-3炔基; R3(在每種情形下)獨立選自Ci-3烷基,羥基,c1-3垸 氧基,F,Cl,Br,I,NR5R5a,n〇2,CN, C(0)R6,NHC(0)R7,及 NHC(0)NR5R5a ; 另一種情形是,若存有2個R3且附接相鄰碳原子時,則 可共同組成·0(:Η20·; R 4選自經0 -1個R3取代之環丙基,經0 - 2個R3取代之 苯基,及經0_1個R3取代之5-6員雜環系統(其内包 括1 - 3個選自氧,氮及硫雜原子),其中雜環系統選 自2 - ρ比淀基,4 -说淀基,2 -咬喃基,3 -吱喃基,2 _ 嘧吩基,3-嘧吩基,2-嘮唑基,2-嘍唑基,4·異$ 唑基,及2 -咪唑基; R5及R5a獨立選自氫,CH3及C2H5 ; R6 選自氫,羥基,Ch3,c2H5,och3,oc2h5,及 NR5R5a ; R7 選自 CH3,C2H5,OCH3,及 OC2H5 ; R8選自氫,CH3及C2H5 ;及 n選自1及2。 [5 ]在另一個較佳的具體實例中,其中的化合物具式I & -12- 本紙張尺度適用中關家標準(T^s) A4規格(210X 297公釐)' '*-- -- (請先閱讀背面之注意事項再填寫本頁) 、11 587078 Α7 Β7 經濟部中央標準局員工消費合作社印製 五、發明説明(10 )Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs, or its stereoisomers or pharmaceutically acceptable salts, where: R1 is a Cl-3 alkyl substituted with 1-7 odontins; R2 is selected from R4 substituted Cl_5 alkyl groups, 1-2 R4 substituted C 2-5 fluorenyl groups, and 1 R 4 substituted C 2 _ 5 alkynyl groups; R3 (in each case) is independently selected In (^ _4 alkyl, OH, Cb4 alkoxy, F, Cl, Br, I ,, NR5R5a, N02, CN, C (0) R6, NHC (0) R7, and NHC (0) NR5R5a, ... In one case, if there are two R3 groups and the adjacent carbon source -9 is attached-this paper size applies the Chinese National Standard (CNS) A4 specification (210 X 297 mm) printed by the Employees' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 587078 kl ____ B7_ V. Description of the invention (7) --- can be combined to form -0CH20-; R4 is selected from 0.2 substituted by 3 R3 (: 3_5 cycloalkyl, substituted by 0_5 R3 Phenyl, and a 5-6 membered heterocyclic system substituted with 0-2 R3 (which contains 1-3 heteroatoms selected from oxygen, nitrogen, and sulfur); R5 and R5a are independently selected from hydrogen and Cw Alkyl; R6 is selected from hydrogen, hydroxy, Cm alkyl, Cm alkoxy, NR5R5a; R7 is selected from Cm alkyl, and Cu alkoxy; R8 is selected from hydrogen, C3.5-cycloalkyl, and C1-3 alkyl; and η is selected from 0,1,2,3, and 4. [2] In a preferred embodiment, the present invention provides a novel compound of formula j, wherein: R1 is a Cu alkyl substituted with 1-7 halogens; R 2 is selected from ci substituted with 1 R4 5 bases, C2-5 fluorenyl substituted with 1 R4, and C2_5 alkynyl substituted with 1 R4; R3 (in each case) is independently selected from Cb4 alkyl, hydroxyl, Cl_4 alkoxy , F, Cl, Br, I, NR5R5a, N02, CN, C (0) R6, NHC (0) R7, and NHC (0) NR5R5a; In the other case, if there are 2 R3 groups, and attached Next to its adjacent carbon atoms, they can be combined together to form _〇CH20-; R4 is selected from C3_5 cycloalkyl substituted with 0-2 R3, phenyl substituted with 0-2 R3, and 5-6 member heterocyclic ring system substituted by R3 (containing 1-3 heteroatoms selected from oxygen, nitrogen, and sulfur); R5 and R5a are independently selected from hydrogen, CH3 and C2H5; -10-this paper is applicable to countries Standard (CNS) A4 (210x297 mm) (Please read the notes on the back before filling in this ) Order 587078 Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs. 5. Description of the invention (8 R is selected from hydrogen, hydroxyl, CH3, C2H5, ocu3, 0CU3, OC2H5, and NR5R5a; R is selected from ch3, C2H5, OCH3, and 〇 c2H5: R8 is selected from hydrazone, cyclopropyl, ch3 and c2h5; and n is selected from 0, 1, 2, and 3. [3] In a more specific embodiment, the present invention provides a novel compound of formula j, wherein: R1 is selected from cf3 and c2f5; R is selected from ci_3 tiger group substituted with 1 R4, and substituted with 1 R4 Pan C 2-3 fluorenyl, and C 2 · 3 block substituted with 1 R 4; R 3 (in each case) is independently selected from Cb 3 alkyl, hydroxyl, Ci 3 cadaveryloxy, F, Cl, Br, I, NR5R5a, N02, CN, C (0) R6, NHC (0) R7, and NHC (0) NR5R5a: Another way is, if there are two R3s and they are attached to Zheng Jinzi, they can be common Composition -0CH20-; and R4 is selected from C3_5 cycloalkyl substituted with 0-2 R3, phenyl substituted with 0-2, and 5-6 membered heterocyclic ring substituted with 0-1 R3 (It includes 1-3 heteroatoms selected from oxygen, nitrogen, and sulfur): R5 and R5a are independently selected from hydrogen, CH3 and C2H5; R6 is selected from hydrogen, hydroxyl, CH3, C2H5, OCH3, oc2i ^ NR5R5a , And C, please read and read the notes on the back and fill in this page)-· R7 is selected from CH3, C2H5, OCH3, 0〇2 and R8 is selected from hydrogen, CH3 and C2H5: and n is selected from 0, 1, and 2 . -11-This paper size applies Chinese National Standard (CNS) A4 (210X 297mm) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 587078 5. Description of the invention (9) [4] In a better specific example, The present invention provides a compound of formula I, wherein: R1 is CF3; R2 is selected from the group consisting of C1 · 3 alkyl substituted with 1 R4, C2_3 alkenyl substituted with 1 R4, and 1 substituted with R4 C2-3 alkynyl; R3 (in each case) is independently selected from Ci-3 alkyl, hydroxy, c1-3 alkoxy, F, Cl, Br, I, NR5R5a, no2, CN, C ( 0) R6, NHC (0) R7, and NHC (0) NR5R5a; Another case is that if there are two R3 and adjacent carbon atoms are attached, they can be composed together · 0 (: Η20 ·; R 4 Selected from cyclopropyl substituted with 0 to 1 R3, phenyl substituted with 0 to 2 R3, and 5-6 membered heterocyclic ring systems substituted with 0_1 to R3 (including 1 to 3 selected from oxygen , Nitrogen and sulfur heteroatoms), in which the heterocyclic system is selected from 2-rhodido, 4-diodonyl, 2-octanoyl, 3-succinyl, 2-pyrimyl, 3-pyrimyl , 2-oxazolyl, 2-oxazolyl, 4-isothiazolyl, and 2-imidazolyl; R5 and R5a are independent Selected from hydrogen, CH3 and C2H5; R6 selected from hydrogen, hydroxy, Ch3, c2H5, och3, oc2h5, and NR5R5a; R7 selected from CH3, C2H5, OCH3, and OC2H5; R8 selected from hydrogen, CH3 and C2H5; and n selected Since 1 and 2. [5] In another preferred specific example, the compound has the formula I & -12- This paper size applies the Zhongguanjia standard (T ^ s) A4 specification (210X 297 mm) '' *--(Please read the precautions on the back before filling out this page), 11 587078 Α7 Β7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs V. Invention Description (10)
la.la.
[6]在另一個較佳的具體實例中,其中的化合物真是 lb ·· —[6] In another preferred embodiment, the compound is really lb ··-
工b.Work b.
[7]在另一個較佳的具體實例中,式I化合物選自:、 ( + /-)-6-氣-4-環丙基乙炔基-4-三氟甲基-3,4-二氫-2(1 氫)-p奎峻17林S同;( + /- )- 6•氯-4-(2 -ρ比淀基)乙块基-4_二氣甲基-3,4 -二氮 -2 (1氫)-p奎峻琳酮; (+ /- )_6-氣-4-苯基乙決基-4-二氣甲基-3,4-二氯-2(1 氫)-p奎峻ττ林酮;(+ /- )_4 -環丙基乙块基-6-甲氧基-4-二氣甲基-3,4_二氯 -2 (1氫)_ p奎峻淋酮; (+ /- )_6 -甲氧基_4_(2-p比淀基)乙块:基-4-二氣曱基-3,4_ 二氫· 2 (1氫)-喹唑啉酮; (+ /- )- 6_甲氧基-4-苯基乙块基-4 -二氟^甲基·3,4 -二鼠- -13 - 本紙張尺度適用中國國家標準(CNS ) Α4規格(210X297公釐) (請先閱讀背面之注意事項再填寫本頁) 587078 經濟部中央標準局員工消費合作社印製 A7 B7五、發明説明(11 ) 2(1氫)-喹唑啉酮; ( + /-)-4-環丙基乙炔基-5,6-二氟-4-三氟甲基-3,4-二氫-2 (1氫)-口奎峻p林酮; (+ /_)_5,6-二氟-4_(2-吡啶基)乙炔基_4-三氟甲基-3,4-二氫-2(1氫)-喹唑啉酮; (+ /- )_5,6_二氣-4-苯基乙決基_4_二氣甲基-3,4 -二氯_ 2(1氫)-喹唑啉酮;( + /- )- 4-環丙基乙块基-6 -說-4-二氣甲基-3,4 -二氮- 2(1 氫)-4峻TT林酮;(+ /- )_6_氣- 4_(2-ρ比淀基)乙块基-4-三氣甲基-3,4_二氯 - 2 (1氫)-p奎峻4酮; ( + /- )- 6-說-4 -苯基乙決基-4-二氣甲基-3,4-二氮- 2(1 氫)-0奎峻淋酮;( + /- )- 6-氣- 4_(2’_2-p比淀基)乙基 _ 4 -二氣甲基-3,4 _ 二 氫-2(1氫)-喳唑啉酮; ( + /-)-6 -氟-4_苯基乙基_4_三氟甲基-3,4_二氫- 2(1 氫)-η奎峻淋酮;(-)-6 -氣-4-環丙基乙块基-4-二氟^甲基-3,4-二氯_2(1 氫)-p奎吐ττ林酮: (+ )- 6•氣_4_環丙基乙決基_4_二氣甲基-3,4-二氮_2(1 氫)· 4峻淋酮; ( + )- 4-環丙基乙決基-5,6-二氣-4-二氣甲基-3,4_二氯· 2(1氫)·喹唑啉酮; (-)-4 -環丙基乙块基- 5,6·二氣-4-二氣曱基-3,4-二鼠- -14-本紙張尺度適用中國國家標準(CNS)A4規格(2l0X297公釐) (請先閱讀背面之注意事項再填寫本頁) 587078 A7 B7 五、發明説明(12 2(1氫)-喹唑啉酮; (+)·4·ε.環丙棊乙烯基.5,6_m甲基_3,4_二 氫-2(1氫)奎吐琳酮; (-)_6-氯-4-E-環丙基乙缔基·4_三氟甲基_3 4_二氫- 2 ( 1氫)·峻峻琳酮; 、、 或其醫藥學上可接受之鹽類。 : m在第二個具體實你]中,本發明提供< π之新颖化合 物: '[7] In another preferred embodiment, the compound of formula I is selected from: (+/-)-6-gas-4-cyclopropylethynyl-4-trifluoromethyl-3,4-di Hydrogen-2 (1 hydrogen) -p Kuijun 17 Lin Stong; (+ /-)-6 • chloro-4- (2-ρ than yodoyl) ethyl block-4_digasmethyl-3,4 -Diazine-2 (1 hydrogen) -p-quinazolinone; (+/-) _ 6-Ga-4-phenylethyl-4-digasmethyl-3,4-dichloro-2 (1 (Hydrogen) -p quinone ττ linone; (+/-) _ 4-cyclopropylethyl-6-methoxy-4-difluoromethyl-3,4_dichloro-2 (1 hydrogen) _ p-quinone ketone; (+ /-) _6 -methoxy_4_ (2-p than ydoyl) ethyl block: yl-4-difluorofluorenyl-3,4_ dihydro · 2 (1 hydrogen)- Quinazolinone; (+ /-)-6-methoxy-4-phenylethyl block-4 -difluoro ^ methyl · 3,4 -dirat--13-This paper size applies to Chinese national standards (CNS) Α4 specification (210X297 mm) (Please read the notes on the back before filling out this page) 587078 Printed by the Consumers Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Invention Description (11) 2 (1H) Azolinone; (+ /-)-4-cyclopropylethynyl-5,6-difluoro-4-trifluoromethyl-3,4-dihydro-2 (1 hydrogen) -Kou Kuijun Ketone; (+ / _) _ 5,6-difluoro-4_ (2- (Pyridyl) ethynyl_4-trifluoromethyl-3,4-dihydro-2 (1hydro) -quinazolinone; (+/-) _ 5,6_digas-4-phenylethoxyl _4_Digasmethyl-3,4-dichloro-2 (1hydro) -quinazolinone; (+ /-)-4-cyclopropylethyl block-6-said 4-digas -3,4 -diaza-2 (1 hydrogen) -4 TT Linone; (+ /-) _6_ gas-4_ (2-ρ than ydenyl) ethyl block-4-trifluoromethyl- 3,4_dichloro-2 (1 hydrogen) -p-quinone 4 ketone; (+ /-) -6-speak-4 -phenylethyl-4-difluoromethyl-3,4-diazine -2 (1 hydrogen) -0 quatridone; (+ /-)-6-gas-4_ (2'_2-p than ydoyl) ethyl_ 4 -digasmethyl-3,4 _ dihydro -2 (1hydro) -oxazolinone; (+ /-)-6 -fluoro-4_phenylethyl_4_trifluoromethyl-3,4_dihydro-2 (1hydro) -η Kui Junlin Ketone; (-)-6-Ga-4-cyclopropylethyl 4-methyl-4-difluoro ^ methyl-3,4-dichloro_2 (1 hydrogen) -p Ketulol ττ Linone: (+)-6 • Gas_4_cyclopropylethenyl_4_digasmethyl-3,4-diazine_2 (1 hydrogen) · 4 Junlinone; (+)-4-cyclopropane -Ethylethenyl-5,6-digas-4-digasmethyl-3,4-dichloro · 2 (1hydro) · quinazolinone; (-)-4 -cyclopropylethyl- 5,6 · Diqi-4-diazimidyl-3,4-dirat--14- Applicable for this paper size National Standard (CNS) A4 (2l0X297 mm) (Please read the precautions on the back before filling out this page) 587078 A7 B7 V. Description of the invention (12 2 (1 hydrogen) -quinazolinone; (+) · 4 · ε. Cyclopropenylvinyl. 5,6_mmethyl_3,4_dihydro-2 (1hydro) quinolone; (-) _ 6-chloro-4-E-cyclopropylethylenyl 4_trifluoromethyl_3 4_dihydro-2 (1 hydrogen). Junjunlinone; or its pharmaceutically acceptable salts. : M in the second concrete example], the present invention provides a novel compound of < π: '
(請先閱讀背面之注意事項再填寫本頁) • -^11 衣. 經濟部中央標準局員工消費合作社印製 或其立體異構物或其醫藥學上可接受之鹽類,其中: R2 是 CeC-R“ R3選自C〗-4烷基,羥基,Ci-4燒氧基,F,Cl,Br, I,NR5R5a,N〇2,CN,C(0)R6,NHC(0)R7,及; NHC(0)NR5R5a ; 尺“選自曱基,乙基,正-丙基,異-丙基,異-丁基,第 三·丁基,及異-戊基; R5及R5a獨立選自氫及Ci-3烷基; R6選自氫,羥基,Ci_4烷基,Cb4烷氧基,及 NR5R5a ; R7選自Cu烷基及Cy烷氧基; -15 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 587078 A7 B7 五、發明説明(13 ) R8選自氫,c3.5環燒基,及Ci 3燒基;及 η選自〇’1,2,3,及4。 、 [9]在另一個較佳具體實例中,本發明提供式π新穎化 合物,其中: R2 是 CEC-R4a 〜 R選自Ch4 基,羥基,Ci 4烷氧基,F,C1,Br、, 1,NR R a,N02,CN,C(0)R6 及 NHC(C))R7 : R選自甲基’乙基,正-丙基,異·丙基,異_ 丁基,第 二-丁基,及異·戊基; ' R5及1153獨立選自氫,CH3及C2H5 ; R 選自氫,羥基,ch3,c2h5,och3,OC2H5,及 NR5R5a ; ^ R7 選自 CH3,C2H5,OCH3,及 〇C2H5 ; R8選自氫,環丙基,CH3及C2H5 ;及 n選自0,1,及2。 [1 Ο ]在另一個較佳具體實例中,其中化合物具式n a (請先閱讀背面之注^^項再填寫本頁) .(Please read the precautions on the back before filling out this page) •-^ 11 Clothing. Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economy or its stereoisomers or its pharmaceutically acceptable salts, where: R2 is CeC-R "R3 is selected from the group consisting of C-4 alkyl, hydroxy, Ci-4 alkyloxy, F, Cl, Br, I, NR5R5a, No2, CN, C (0) R6, NHC (0) R7 , And; NHC (0) NR5R5a; "selected from fluorenyl, ethyl, n-propyl, iso-propyl, iso-butyl, tert-butyl, and iso-pentyl; R5 and R5a are independent It is selected from hydrogen and Ci-3 alkyl; R6 is selected from hydrogen, hydroxyl, Ci_4 alkyl, Cb4 alkoxy, and NR5R5a; R7 is selected from Cu alkyl and Cy alkoxy; -15 This paper size applies to Chinese national standards (CNS) A4 specification (210X297 mm) 587078 A7 B7 V. Description of the invention (13) R8 is selected from hydrogen, c3.5 cycloalkyl, and Ci 3 alkyl; and η is selected from 0'1,2,3, And 4. [9] In another preferred embodiment, the present invention provides a novel compound of formula π, wherein: R2 is CEC-R4a ~ R is selected from the group consisting of Ch4, hydroxyl, Ci 4 alkoxy, F, C1, Br ,, 1, NR R a, N02, CN, C (0) R6 and NHC (C)) R7: R is selected from methyl'ethyl, n-propyl, isopropyl, iso-butyl, and second- Butyl, and isopentyl; 'R5 and 1153 are independently selected from hydrogen, CH3 and C2H5; R is selected from hydrogen, hydroxyl, ch3, c2h5, och3, OC2H5, and NR5R5a; ^ R7 is selected from CH3, C2H5, OCH3, And oC2H5; R8 is selected from hydrogen, cyclopropyl, CH3 and C2H5; and n is selected from 0, 1, and 2. [10] In another preferred embodiment, the compound has the formula n a (please read the note ^^ on the back before filling this page).
、1T 經濟部中央標準局員工消費合作社印製Printed by 1T Consumer Cooperatives, Central Standards Bureau, Ministry of Economic Affairs
[11]在另一個較佳具體實例中,其中化合物具式nb -16- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X 公釐) 587078 A7 B7 五、發明説明(14 )[11] In another preferred embodiment, the compound has the formula nb -16- The paper size is applicable to the Chinese National Standard (CNS) A4 specification (210X mm) 587078 A7 B7 V. Description of the invention (14)
lib. 經濟部中央標準局員工消費合作社印製 [12]在另一個更佳的具體實例中,式II化合物選自: ( + /-)-6-氯-4_異丙基乙炔基-4-三氟甲基-3,4-二氫_i(l 氫)-η奎也淋酮; ( + /- )- 6-氣-4 -乙基乙块基_4_三氣甲基-3,4·^^氯- 2(1 氫)-π奎峻琳酮; ' ( + /- )- 4-異丙基乙块基-6-曱氧基·4 -三氣甲基-3,4 -二氯 -2(1氫)_ρ奎峻琳酮; ( + /- )- 5,6 -二氟_4·異丙基乙決基-4-三氟甲基-3,4 -二氫 •2(1氫)-喹唑啉酮;, ( + /- )- 5,6 -二說-4 -乙基乙块秦-4-三氟甲基_3,4 -二氯-2(1氫)-p奎峻琳酮; ( + /-)-5,6二氟 _4·異戊基-4·三氟、甲基 _3,4·二氫-2(1 氫)· p奎峻淋酮; (+ /- )- 6-氣-4-異丙基乙块基-4_二象曱基-3,4-二氮-2(1 氫)-ρ奎峻淋酮; ( + /-)-6 -氟-4 -乙基乙炔基-4-三氟甲基-3,4·二氫- 2(1 氫)—奎峻淋酮; (-)-5,6_二氟_4_異丙基乙炔基-4-三氟甲基-3,4-二氫· 2(1氳)_喹唑啉酮; ( + )- 5,6-二氟-4-異丙基乙块基-4-三氣甲基-3,4_二氫- -17- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X 297公釐) (請先閱讀背面之注意事項再填寫本頁) 587078 Μ Β7 五、發明説明(15 ) ( 2(1氫)·喹唑啉酮; (-)-5,6•二氣_4_乙基乙块基-4 -三氟^甲基- 3,4 -二氯- 2(1 氫)· p奎峻p林酮; (+ )- 5,6-二氣-4_乙基乙块基-4_二氣甲基-3,4-二鼠-2 (1氫) p奎峻4酮; 或其醫藥學上可接受之鹽類。 在第三個具體實例中,本發明提供一種新穎之醫藥組合 物,其内包括醫藥學上可接受之載體及具療效含量之式I 或II化合物,或其醫藥學上可接受之鹽類。 在第四個具體實例中,本發明提供一種治療HIV感染之 新穎方法,其包括對需要此種治療的宿主投與療效含量之 式I或II化合物或其醫藥學上可接受之鹽類。 在第五個具體實例中,本發明提供一種治療HI V感染之 新穎方法,其包括對需要此種治療的宿主共同投與療效含 量之: (a) 式I或II化合物;及 (b) 至少一種選自HIV逆轉錄酶抑制劑及HIV蛋白酶 抑制劑。 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) 在另一個較佳的具體實例中,逆轉錄酶抑制劑選自AZT, 3TC,ddl, ddC,d4T ,(戴樂凡丁)delavirdine TIBO 衍生 物,BI-RG-587 ,(那凡樂平)nevirapine,L_697,661, LY73497, Rol8,893 ,(樂凡力)loviride ,(克凡 丁)trovirdine, MKC-442,及 HBY 097,而蛋白酶抑制劑選 自(塞克凡)saquinavir ,(力特那凡)ritonavir,(因丁那 -18- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 587078 A7 B7 五、發明説明(16 凡)indinavir,VX_478 ,(那夫那凡)nelfinavir,KNI-272, CGP-61755, U-140690,及 ABT-378。 在另一個更佳的具體實例中,逆轉錄酶選自Αζτ及 3TC,而蛋白酶抑制劑選自(赛克凡),(力特那 凡)ritonavir ,(那夫那凡)nelfinavir ,及(因丁那 凡)indiavir 〇 在另一個最佳的具體實例中,逆轉綠酶抑制劑是Αζτ。 在另一個最佳的具體實例中,蛋白酶抑制劑是(因丁那 凡)indinavir 〇 在第六個具體實例中,本發明提供一種用於治療mv感 染<醫藥套組,在一個或多個無菌容器中,其包括療效含 量之: (a) 式I或II化合物;及 (b) 至少一種選自HIV逆轉綠酶抑制劑及mv蛋白酶 抑制劑。 在第七個具體實例中,本發明提供—種抑制存於體液樣 品中HIV之新穎方法,其包括以療效含量式!或η化合物 處理體液樣品。 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) 在第八個具體實例中,本發明楹供 贫月徒供一種新穎的套組或容 器,其包括於測試或分析時用作爲標準或試劑的有效含量 之式I或II化合物,以測定抑制HIV逆轉綠酶,猜^長 (或兩者)之潛在醫藥能力。 本説明書種所用之名詞及表示法定轟1 疋我如下,需了解的是 -19- 587078 五、發明説明(17 經濟部中央標準局員工消費合作社印製 本發明化合物含有-個非對稱碳原子,故分 =形式或是消旋形式。技藝中已熟知如何製備光 /式’ ★如消旋形式的分解作用,或自光學活性起始 以合成作用製備之。除非特別表明特異性異構物形式或異 構物形式,否則均包括結構之所有的對掌中心,非立體里 構物,消旋形式及所有的幾何異構物。 " 完成本發明方法至少是數克規模,公斤規模,數公斤規 模,或是工業規模,本説明書中數克規模是較佳的,其所 用之起始物質至少是1G克或多於1G克,更佳的是至少5〇 克或多於5G克,最佳的是至少⑽克或多於i⑼克。本説 明書中數公斤規模意指至少一種所用的起始物質多於〗公 斤,本説明書種所用工業規模意指除了實驗室外的規模, 能對臨床測試或廣大消費者足以供應充分的產品。 本發明書中所用”烷基”意指包括具特定碳原子數目且可 爲支鏈或直鏈飽和之脂肪族碳氫基團,烷基的範例包括(但 不偈限於)甲基’乙基,正-丙基,異-丙基,正_ 丁基,第 二-丁基,第三-丁基,正_戊基,及第二·戊基。”鹵素烷 基’’意指具特足碳原子數目且可經丨或多個齒素取代之支鏈 或直鏈飽和脂肪族碳氫基團(例如_ CvFw,其中v= 1至3而 w - 1至(2 v + 1 ))’鹵素燒基的範例包括(但不侷限於)三氟 甲基,三氣甲基,五氟甲基,及五氣甲基。”烷氧基,,定義 如燒基定義,而所指的碳原子是以氧爲鍵橋鍵結的,烷氧 基的範例包括(但不侷限於)甲氧基,乙氧基,正-丙氧基, 異-丙氧基,正-丁氧基,第二-丁氧基,第三-丁氧基,正- (請先閱讀背面之注意事項再填寫本頁) 訂 -20- 本紙張尺度適用中國國家標準(CNS ) A4規格(21〇><297公髮) A7 B7 五、發明説明(18 ) ^ f氧基,及第二_戊氧基。,,環烷基,,意指含有飽和環,諸如 裱丙基,環丁基,或環戊基。,,烯基,,意指在直鏈或支鏈結 構上任何穩定鍵結處具有一個或多個不飽和碳—碳雙鍵,'諸 如乙烯,丙晞及其類似者。”炔基,,意指在直鏈或支鏈結構 上任何穩定鍵結處具有一個或多個不飽和碳_碳三鍵,^如 乙炔,丙块,及其類似者。 本説明書中所用,,齒素,,意指氟,氣,溴及碘。,,本發明書 中所用相對離子意指一種微小,負電荷離子,諸如氯離 子,溴離子,羥離子,醋酸根離子,硫酸根離子及類似 本發明書中所用,,芳香基,,或,,芳香基殘基”意指具有特定 碳原子數目之芳香族部分,諸如苯基或莕基。本發明所用,, 碳環’或”碳環殘基,,意指任何3_至5_員穩定之單環結構, 其可爲飽和或不飽和,此種碳環的範例包括(但不侷限於) 環丙基’環戊基,環己基,苯基,雙苯基,蕃基"㈣ 基,金剛烷基,或四氫萘基(四氫莕)。 經濟部中央標準局員工消費合作社印製 本發明所用,,雜環,,或,,雜環系統,,意指5_至6_員之穩定 單雜環,其可爲飽和,部分不飽和,或不飽和(芳香族), 其由碳原子及1至3個獨立選自氮,氧及硫之雜原子所組 成,氮及硫雜原子可視情況氧化之。雜環上任何雜原子或 碳原子可键結至其附屬基團上而產生穩定的結構。假若所 產生的化合物穩定,則本説明書中所述之雜環系統碳或氮 原子上可經取代,若特別提及,雜環上的氮原子視情況可 爲四級化。雜環中的硫及氧原子總數超過丨,且這些雜原lib. Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs [12] In another preferred embodiment, the compound of formula II is selected from: (+ /-)-6-chloro-4_isopropylethynyl-4 -Trifluoromethyl-3,4-dihydro_i (l hydrogen) -η quinoxalenone; (+ /-)-6-Ga-4 -ethylethyl block_4_trigasmethyl- 3,4 · ^^ chloro-2 (1 hydrogen) -π-quizonlinone; '(+ /-)-4-isopropylethyl-6-fluorenyloxy · 4-trifluoromethyl-3 , 4 -dichloro-2 (1hydro) _ρ kujunlinone; (+ /-)-5,6 -difluoro-4 · isopropylethyl-4-trifluoromethyl-3,4- Dihydro • 2 (1hydro) -quinazolinone; (+ /-)-5,6 -bis-a-4 -ethylethyl block Qin-4-trifluoromethyl_3,4 -dichloro- 2 (1 hydrogen) -p quinjunlinone; (+ /-)-5,6 difluoro-4 · isoamyl-4 · trifluoro, methyl_3,4 · dihydro-2 (1 hydrogen) · P-quinone ketone; (+ /-)-6-Ga-4-isopropylethyl block-4_diamidino-3,4-diaza-2 (1 hydrogen) -ρ quinone Ketones; (+ /-)-6 -fluoro-4 -ethylethynyl-4-trifluoromethyl-3,4 · dihydro-2 (1 hydrogen)-quinazone; (-)-5, 6_difluoro_4_isopropylethynyl-4-trifluoromethyl-3,4-dihydro · 2 (1 氲) _quinazolinone; (+)-5,6-difluoro-4 -different Ethyl block-4-trimethyl-3,4_dihydro--17- This paper size applies to China National Standard (CNS) A4 (210X 297 mm) (Please read the precautions on the back before filling This page) 587078 Μ B7 V. Description of the invention (15) (2 (1 hydrogen) · quinazolinone; (-)-5,6 • digas_4_ethylethyl block-4 -trifluoro ^ A -3,4 -dichloro-2 (1 hydrogen) · p-quinone plinone; (+)-5,6-diazine-4_ethylethyl block-4_diazylmethyl-3, 4-Dimur-2 (1 hydrogen) p-quinone 4 ketone; or a pharmaceutically acceptable salt thereof. In a third specific example, the present invention provides a novel pharmaceutical composition, including medicine A carrier and a therapeutically effective amount of a compound of formula I or II, or a pharmaceutically acceptable salt thereof. In a fourth specific example, the present invention provides a novel method for treating HIV infection, which includes the need for The host of such treatment administers a therapeutically effective amount of a compound of Formula I or II or a pharmaceutically acceptable salt thereof. In a fifth specific example, the present invention provides a novel method for treating HIV infection, which includes the need for The place for this treatment Therapeutically effective amount of co-administered comprising: or II (a) of formula I; and (b) at least one compound selected from HIV reverse transcriptase inhibitors and HIV protease inhibitors. Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (please read the notes on the back before filling this page) In another preferred specific example, the reverse transcriptase inhibitor is selected from AZT, 3TC, ddl, ddC, d4T, (Da Le Fan Ding) delavirdine TIBO derivative, BI-RG-587, (Na Fan Le Ping) nevirapine, L_697,661, LY 73497, Rol 8,893, (Luo Fan Li) loviride, (Ke Fanding) trovirdine, MKC-442, And HBY 097, and the protease inhibitor is selected from (Sekfan) saquinavir, (ritnavir) ritonavir, (Indina-18- This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) 587078 A7 B7 V. Description of the invention (16 Fans) indinavir, VX_478, (Nafnafan) nelfinavir, KNI-272, CGP-61755, U-140690, and ABT-378. In another better specific example, the inverse Transcriptase is selected from Αζτ and 3TC, and protease inhibitor is selected from (Secfan), (Litnavan) ritonavir, (Nafnavan) nelfinavir, and (Indinavan) indiavir 〇 In another best Specific example The agent is Ατ. In another preferred embodiment, the protease inhibitor is (indinavir) indinavir. In a sixth embodiment, the present invention provides a pharmaceutical kit for treating mv infection < In one or more sterile containers, it comprises a therapeutically effective amount of: (a) a compound of formula I or II; and (b) at least one selected from the group consisting of HIV reversal green enzyme inhibitors and mv protease inhibitors. In a seventh specific example The present invention provides a novel method for inhibiting HIV stored in body fluid samples, which includes treating body fluid samples with the therapeutic content formula! Or η compounds. Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back first) (Fill in this page) In an eighth specific example, the present invention provides a novel kit or container for the poor, including a compound of formula I or II that is used as a standard or an effective amount of a reagent for testing or analysis, To determine the potential medical ability to inhibit HIV's reversal of green enzymes, guess the long (or both). The terms used in this manual and their legal meanings 1 1 I am as follows, what you need to know is -19- 587078 Description of the invention (17 Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs, the compound of the invention contains an asymmetric carbon atom, so it is divided into a form or a racemic form. How to prepare light / formula is well known in the art. Formal disintegration, or synthetically initiated from optical activity. Unless specific isomeric forms or isomeric forms are specifically indicated, all palmar centers, nonstereomeric forms, racemic forms, and all geometric isomers of the structure are included. " The method for completing the present invention is at least a few grams scale, a kilogram scale, a few kilogram scale, or an industrial scale. A few grams scale is preferred in this specification, and the starting material used is at least 1G grams or more than 1G. Grams, more preferably at least 50 grams or more than 5G grams, and most preferably at least gram or more than iG. The scale of several kilograms in this specification means that at least one of the starting materials used is more than one kilogram. The industrial scale used in this specification means the scale outside the laboratory, which can be sufficient for clinical testing or the general consumer to supply sufficient products . "Alkyl" as used in the present invention means including aliphatic hydrocarbon groups having a specific number of carbon atoms and which may be branched or linear saturated. Examples of alkyl groups include, but are not limited to, methyl'ethyl , N-propyl, iso-propyl, n-butyl, second-butyl, third-butyl, n-pentyl, and second-pentyl. "Haloalkyl" means a branched or straight-chain saturated aliphatic hydrocarbon group (e.g., _ CvFw, where v = 1 to 3 and w -1 to (2 v + 1)) 'Examples of halogenated alkyl groups include, but are not limited to, trifluoromethyl, trifluoromethyl, pentafluoromethyl, and pentafluoromethyl. "Alkoxy ,, The definition is as defined for alkynyl, and the carbon atom referred to is bonded with oxygen as a bridge. Examples of alkoxy include (but are not limited to) methoxy, ethoxy, n-propoxy, iso- Propoxy, n-butoxy, second-butoxy, third-butoxy, n- (Please read the notes on the back before filling out this page) Order-20- This paper size applies to Chinese national standards (CNS) A4 specifications (21〇 < 297 issued) A7 B7 V. Description of the invention (18) ^ foxy, and second pentyloxy. ,, cycloalkyl, is meant to contain a saturated ring, such as propyl, cyclobutyl, or cyclopentyl. ,, alkenyl, means having one or more unsaturated carbon-carbon double bonds at any stable bond on a straight or branched chain structure, such as ethylene, propionate and the like. "Alkynyl" means one or more unsaturated carbon-carbon triple bonds at any stable bond on a straight or branched chain structure, such as acetylene, propyl block, and the like. As used in this specification Tooth element means fluorine, gas, bromine and iodine. The relative ion used in the present invention means a small, negatively charged ion, such as chloride, bromide, hydroxyl ion, acetate ion, sulfate Ionic and similarly used in the present invention, "aryl group, or," aryl group residue "means an aromatic moiety having a specific number of carbon atoms, such as phenyl or fluorenyl. As used herein, "carbocyclic ring" or "carbocyclic residue" means any 3- to 5-membered stable monocyclic structure, which may be saturated or unsaturated. Examples of such carbocyclic rings include (but are not limited to) Yu) Cyclopropyl'cyclopentyl, cyclohexyl, phenyl, bisphenyl, Fanyl " fluorenyl, adamantyl, or tetrahydronaphthyl (tetrahydronaphthyl). Consumer Cooperatives, Central Standards Bureau, Ministry of Economic Affairs For the printing of the present invention, a heterocyclic ring, or a heterocyclic ring system, means a 5- to 6-membered stable single heterocyclic ring, which may be saturated, partially unsaturated, or unsaturated (aromatic), It consists of carbon atoms and 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and nitrogen and sulfur heteroatoms can be oxidized as appropriate. Any heteroatom or carbon atom on the heterocycle can be bonded to its subsidiary group If the compound produced is stable, the carbon or nitrogen atom of the heterocyclic ring system described in this specification may be substituted. If specifically mentioned, the nitrogen atom on the heterocyclic ring may be four as the case may be. Hierarchy. The total number of sulfur and oxygen atoms in the heterocycle exceeds 丨, and these heterogens
本紙張尺度適用中國國家襟準(CNS ) Α4規格(21〇>^^^y 587078 Μ Β7 經濟部中央標準局員工消費合作社印製 五、發明説明(19 ) 子彼此不相接時是較佳的,雜環上硫及氧原子總數不超過 1時是較佳的。本説明書中所用,,芳香雜環系統,,意指任何 穩定之5-至6_單雜芳香環,其由碳原子及i至3個獨立選 自氮,氧及硫雜原T所組成,彡香雜環中硫及氧原子的總 數不超過1時是較佳的。 & 雜環範例包括(但不局限於)2_吡咯啶酮基,2氫·吡咯 基,4-吡啶酮基,6氫-i,2,%嘧二畊基,2氫,6氫· 1,5,2-二嘧畊,呋喃基,呋咕基,四氫咪唑基,咪唑啉 基,咪唑基,異呤唑基,嗎啉基,嘮二唑基,号二 唑基,1,2,4·喝二唑基,υ,%呤二唑基,^,拉呤二 &基’ 基ϋ基,六氣Μ基,六氣说淀基"業 啶基,六氫吡啶酮基,4-六氫吡啶酮基,喋啶基,嘌呤 基,哌喃基,吡畊基,吡唑啶基,吡唑啉基,吡唑基,塔 畊基,呲啶基,吡啶基,嘧啶基,吡咯啶基,吡咯啉基, 吡咯基,四氫呋喃基,6Η·1,2,5_硫二卩井基,硫二 畊基,1,2,4-硫二畊基,硫二畊基,^,扣硫二 畊基,噻唑基,嘍吩基,嘍吩嘧唑基,嘍吩呤唑基,嘍吩 咪唑基,嘍吩基,三唑基,三唑基,u2,4•三唑 基’ 1,2,5-三峻基,及nr三峻基。較佳的雜環包括 (但不局限於)吡啶基,呋喃基,嘍吩基,吡咯基,吡唑 基,咪唑基及嘮唑基,亦包括含有前述雜環之融合環及旋 轉化合物。 本説明書中所用’’HIV逆轉綠酶抑制劑,,意指mv逆轉綠 酶(RT)之核替及非核替抑制劑,核替抑制劑的範例包括 -22- 本紙張尺度適用中國國家標準(CNS ) Α4規格(210^97^ (請先閲讀背面之注意事項再填寫本頁) • 衣·This paper size applies to China National Standards (CNS) A4 specifications (21〇 &^; ^^^ y 587078 Μ B7) Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 5. The invention description (19) Preferably, the total number of sulfur and oxygen atoms on the heterocyclic ring does not exceed 1. As used in this specification, the aromatic heterocyclic ring system means any stable 5- to 6-monoheteroaromatic ring, which is composed of Carbon atoms and i to 3 are independently selected from the group consisting of nitrogen, oxygen, and thiagen T, and it is preferred that the total number of sulfur and oxygen atoms in the fragrant heterocyclic ring does not exceed 1. & Examples of heterocyclic rings include (but not Limited to) 2-pyrrolidinone, 2-hydropyrrolidinyl, 4-pyridone, 6-hydro-i, 2,% pyrimidinyl, 2 hydrogen, 6-hydropyridinyl , Furyl, furfuryl, tetrahydroimidazolyl, imidazolinyl, imidazolyl, isoroxazolyl, morpholinyl, oxadiazolyl, diazolyl, 1,2,4 υ,% pyridazolyl, ^, laridine di & yl ', methyl, hexafluoromethyl, hexamethylpyridyl, < pyridyl, hexahydropyridone, 4-hexahydropyridone , Pyridinyl, purinyl, piperidine , Pyrimidinyl, pyrazolyl, pyrazolinyl, pyrazolyl, targonyl, pyridinyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolinyl, pyrrolyl, tetrahydrofuranyl, 6Η · 1,2,5_Sulfuric acid base, sulfuric acid base, 1,2,4-sulfuric acid fertilization base, sulfuric acid fertilization base, ^, sulfuric acid fertilization base, thiazolyl, fluorenyl, fluorenyl Pyrimazolyl, phenphenazolyl, phenphenimidazolyl, phenphenyl, triazolyl, triazolyl, u2,4 • triazolyl'1,2,5-trisyl, and nrtrisyl Preferred heterocycles include, but are not limited to, pyridyl, furyl, pyrenyl, pyrrolyl, pyrazolyl, imidazolyl, and oxazolyl, as well as fusion rings and spin compounds containing the aforementioned heterocycles. The term "HIV reversal green enzyme inhibitor" used in this specification means the replacement and non-reversion inhibitors of mv reversal green enzyme (RT). Examples of nuclear reversion inhibitors include -22- This paper applies Chinese national standards (CNS) Α4 specifications (210 ^ 97 ^ (Please read the precautions on the back before filling out this page) • Clothing ·
、1T 587078 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明(2〇 ) (但不局限於)AZT,ddC,ddl,dT4及3TC,非核苷RT 抑制劑包括(但不偈限於)戴樂凡丁(delavirdine)(法馬西亞 及普強U90152S),TIBO衍生物,BI-RG-587,那凡樂平 (nevirapine)(柏林格殷吉漢),L-697,661,LY73497,Ro 18,893(羅奇),樂凡力(l〇viride)(傑申),特凡丁 (trovirdine)(禮來),MKC-442(特安格),及 HB Y 097(赫 斯特)。 本説明書中所用’’HIV蛋白酶抑制劑,’意指能抑制HIV蛋 白酶之化合物,範例包括(但不侷限於)賽克那凡 (saquinavir)(羅奇,R〇3 1-8959),力特那凡(ritonavir)(亞 伯特,ABT-538),因 丁那凡(indinavir)(默克,MK-639), VX-478(福特克斯/格羅素威爾康),那夫那凡 (nelfnavir)(阿格羅恩,AG-1343),KNI-272(日本恩能 吉),CGP-61755(西巴-吉格),U-140690(法馬西亞吉普 強),及ABT-3 78。其他包括環狀蛋白酶抑制劑的範例揭示 於 W0 93/07128,W0 94/19329,W0 94/22840,及 PCT 專利文件US 96/03426。 本説明書中所用”醫藥學上可接受之鹽類,,意指所揭示之 化合物的衍生物,是將母化合物修飾成其酸加成鹽或鹼加 成鹽。醫藥學上可接受之鹽類的範例包括(但不侷限於)鹼 性殘基(諸如胺類)之礦物或有機酸鹽類,·酸性殘基(諸如羧 酸)之鹼性或有機,鹽類;及其類似者。醫藥學上可接受之鹽 類包括,例如,以無毒無機酸或有機酸所形成母化合物的 慣用無毒性鹽類或四級銨鹽,例如此種慣用無毒鹽類包括 -23 - 本紙張尺度適用中國國家標準(CNS ) A4規格(210x297公釐) (請先閱讀背面之注意_事項再填寫本頁) 、τ 587078 Μ 五、發明説明(21 衍生自無機酸,諸如氫氣酸,氫溴酸,硫酸,胺磺酸,磷 酸,硝酸及類似者;衍生自有機酸者包括乙酸,丙酸,琥 珀酸,羥乙酸,硬脂酸,乳酸,蘋果酸,酒石酸,檸檬 酸,壞血酸,帕馬酸,馬來酸,經基馬來酸,苯乙酸,魏 胺酸,苯甲酸,水楊酸,磺胺酸,2_乙醯氧苯甲酸,延胡 索酸,甲苯磺酸,甲烷磺酸,乙烷磺酸,乙烷二磺酸,草 酸,2 -羥乙磺酸,及類似者。 利用傳統的化學方法可自内含鹼性部份或酸性部分之母 化合物合成本發明醫藥學上可接受之鹽類。通常,在水中 或在有機溶劑中,或兩者之混合液中,將這些化合物的游 離酸或鹼形式與化學量數含量之適當鹼或酸反應後,可製 備此種鹽類;通常,非水基質,如乙醚,乙酸乙酯,乙 醇,異丙醇,或乙腈較佳。合適的鹽類列於Remington,s Pharmaceutical Sciences,17版,麥克出版公司,伊斯頓, PA,1985,1418頁,此文獻中所揭示者併入本發明參考。 本説明書中所用”醫藥學上可接受,,一詞意指在安全的醫 藥用藥上’所用的這些化合物,物質,組合物及/或劑量形 式適合用以與人及動物接觸的,且不會產生過度之毒性, 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁} 、1Τ 刺激,過敏反應,或其他的問題或具合理效益/風險之併發 症0 “前藥”意指包括當哺乳動物投與該種前藥時,可於活體 内釋放出共價鍵結載體上之根據式(I)或其他化學式或本發 明化合物,本發明化合物前藥(例如式(I))是修飾化合物上 所存的官能基,如此經一般施用後,或於活體内可切除修 • 24 - 587078 經濟部中央標準局員工消費合作社印製 A7 —---_______B7 五、發明説明(22 ) 一 飾而成母化合物,本發明化合物包括之前藥是當哺乳動物 投與前藥時,其鍵結至任何基團上的羥基或胺基會切除而 分別形成游離的羥基或游離的胺基。前藥的範例包括(但不 侷限於)醇類之乙酸,甲酸及苯甲酸衍生物及本發明化合物 上之胺基官能基,與類似者。 穩定的化合物”及”穩定的結構,,意指該化合物足以自反 應展合物中穩健的純化成有效的程度,並調配成具療效的 製劑。本發明只製備穩定的化合物。 經取代意指當所用的原子正常價數不超過時,在所表 不結構上的一個或多個氫經所選定之基團,,取代,,,而取代 結果產生是穩定的化合物,當取代基是酮基(即=〇)時,則 有兩個氫原子被取代。 “治療含量’,意指包括能有效抑制HIV感染或治療宿主感 染症狀時所用之本發明化合物含量或組合式化合物的含 量,組合式化合物是較佳的相乘性組合方式,相乘性的範 例如周(Chou)及沓刺來(Talalay) AdvEnzyme Re㈣ 22 : 2^-55 (1984)所述,當投與組合式化合物時的效果(此情況 是抑制HIV的複製)比投與單一試劑之化合物的加成效果 好,通常,投與低於最高濃度之化合物時相乘性效果是最 明顯的,以另一種角度看相乘性是指細胞毒性低,抗病毒 政果增加’或是具有其他各種成分的組合式效益。 合成作用 熟悉有機合成技藝者可以數種已知方式製備本發明化合 物,可用以下所述的方法,配合有機合成技藝中已知的人 -25- I I ί m i ί ϋ ί I (請先閱讀背面之注意事項再填寫本頁) 訂 本紙張尺度適用中國國家榡準TiSs ) Α4規格(210X297公慶) "〜------ 五、發明説明(23 悉::者所了解的方法合成本發明化< 所列的參考限於)以下料料法,以1 流程1 01T 587078 A7 B7 printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (20) (but not limited to) AZT, ddC, ddl, dT4 and 3TC, non-nucleoside RT inhibitors include (but not limited to) ) Delavirdine (Famasia and Puqiang U90152S), TIBO derivative, BI-RG-587, nevirapine (Berlin Geinjihan), L-697,661, LY73497, Ro 18,893 , 10 viride (Jeshen), trovirdine (Lilly), MKC-442 (Teinger), and HB Y 097 (Hurst). As used herein, `` HIV protease inhibitor, '' means a compound capable of inhibiting HIV protease. Examples include, but are not limited to, saquinavir (Roche, R03 1-8959). Ritonavir (Abbott, ABT-538), Indinavir (Merck, MK-639), VX-478 (Fordtex / Grossell Wilcon), Naffna Nelfnavir (Agron, AG-1343), KNI-272 (Engenji, Japan), CGP-61755 (Siba-Gig), U-140690 (Famacia Jeep Strong), and ABT- 3 78. Other examples including cyclic protease inhibitors are disclosed in WO 93/07128, WO 94/19329, WO 94/22840, and PCT patent document US 96/03426. "Pharmaceutically acceptable salts" as used in this specification means derivatives of the disclosed compounds, which are modified from the parent compound to its acid or base addition salt. Pharmaceutically acceptable salts Examples of classes include, but are not limited to, mineral or organic acid salts of basic residues (such as amines), basic or organic, salts of acidic residues (such as carboxylic acids); and the like. Pharmaceutically acceptable salts include, for example, customary non-toxic salts or quaternary ammonium salts of parent compounds formed from non-toxic inorganic or organic acids, such as such customary non-toxic salts including -23-this paper standard applies China National Standard (CNS) A4 specification (210x297 mm) (Please read the notes on the back before filling this page), τ 587078 Μ 5. Description of the invention (21 Derived from inorganic acids such as hydrogen acid, hydrobromic acid, Sulfuric acid, sulfamic acid, phosphoric acid, nitric acid and the like; those derived from organic acids include acetic acid, propionic acid, succinic acid, glycolic acid, stearic acid, lactic acid, malic acid, tartaric acid, citric acid, ascorbic acid, Parma Acid maleic acid Maleic acid, phenylacetic acid, pivalic acid, benzoic acid, salicylic acid, sulfanilic acid, 2-acetamoxybenzoic acid, fumaric acid, toluenesulfonic acid, methanesulfonic acid, ethanesulfonic acid, ethanesulfonic acid, oxalic acid , 2-isethionate, and the like. The pharmaceutically acceptable salts of the present invention can be synthesized from the parent compound containing a basic or acidic portion by conventional chemical methods. Generally, in water or in organic These salts can be prepared by reacting the free acid or base form of these compounds with a suitable base or acid in a stoichiometric amount in a solvent, or a mixture of the two; usually, non-aqueous substrates, such as ether, acetic acid Ethyl esters, ethanol, isopropanol, or acetonitrile are preferred. Suitable salts are listed in Remington, s Pharmaceutical Sciences, 17th Edition, Mike Publishing, Easton, PA, 1985, p. 1418, as disclosed in this document. Incorporated herein by reference. The term "pharmaceutically acceptable," as used in this specification, means that the compounds, substances, compositions, and / or dosage forms used in safe medicinal use are suitable for use with humans and Contacted by animals, and Can produce excessive toxicity, 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 out this page), 1T stimulation, allergic reactions, or other problems or complications with reasonable benefits / risks 0 "Prodrug" is meant to include a compound according to formula (I) or another chemical formula or a compound of the present invention, which is a prodrug of a compound of the present invention ( For example, formula (I)) is a functional group stored on a modified compound, so it can be removed after being applied in general or in vivo. • 24-587078 Printed by A7, Consumer Cooperative of the Central Standards Bureau, Ministry of Economic Affairs. Description of the invention (22) A decorated parent compound, the compounds of the present invention include prodrugs. When a mammal administers a prodrug, the hydroxyl or amine group bonded to any group will be cut off to form a free hydroxyl or Free amine group. Examples of prodrugs include, but are not limited to, acetic acid, formic acid and benzoic acid derivatives of alcohols and amine functional groups on compounds of the present invention, and the like. "Stable compound" and "stable structure" mean that the compound is sufficiently purified robustly from the reaction complex to an effective level, and is formulated into a therapeutically effective preparation. The present invention prepares only stable compounds. Substitution means that when the normal valence of the atom used does not exceed, one or more hydrogens on the indicated structure are replaced by the selected group, and the substitution results in a stable compound. When substituted When the group is a keto group (that is, = 0), two hydrogen atoms are substituted. "Therapeutic content" means the content of the compound of the present invention or the content of a compound of a combination formula which can effectively inhibit the infection of HIV or treat the symptoms of host infection. The compound of a combination formula is a preferred multiplicative combination mode, and a multiplicative example As described in Chou and Talalay AdvEnzyme Re㈣ 22: 2 ^ -55 (1984), the effect when a combination compound is administered (in this case, the inhibition of HIV replication) is greater than that when a single agent is administered The addition effect of the compound is good. Generally, the multiplicative effect is the most obvious when the compound is administered below the highest concentration. From another perspective, the multiplicative effect means that the cytotoxicity is low and the antiviral effect is increased. Combined benefits of various other ingredients. Synthetic effect Those skilled in organic synthesis techniques can prepare the compounds of the present invention in several known ways, which can be combined with those known in organic synthesis techniques by the methods described below -25 mi ί ϋ ί I (Please read the precautions on the back before filling this page) The size of the paper used in this edition is applicable to China ’s national standard TiSs. Α4 specification (210X297 public celebration) " Ming (23 :: The method known to the person who synthesizes the present invention < The listed references are limited to) The following materials method, with 1 process 1 0
RR
/C〇〇H hn(ch3)〇ch] 、顧:> ^—~/ C〇〇H hn (ch3) 〇ch], Gu: ^-~
'N .OCH3 CM,'N .OCH3 CM,
Nib. THSCl ,給基 RxMgX ,Nib.THSCl, RxMgX,
經濟部中央標準局員工消費合作社印製 流程1説明以合適的取代性2-胺基苯甲酸製備酮_苯胺, 此酸轉換成N_甲氧基-N·甲基醯胺衍生物,其後再被取代 成R1-取代酮,酮_苯胺可作爲本發明專利申請範圍化合物 之中間物質。 ^ , 流程2Printing process 1 of the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs illustrates the preparation of keto_aniline with suitable substituted 2-aminobenzoic acid, and this acid is converted into N_methoxy-N · methylamidine derivatives, and thereafter Then it is substituted into R1-substituted ketone, and keto-aniline can be used as an intermediate substance of the compounds in the scope of the present patent application. ^, Flow 2
I2 , NaIIC〇3I2, NaIIC〇3
NibNib
I Me3CCOCl NaIIC03 —-卜 nh2 n ~ Bu LiI Me3CCOCl NaIIC03 --- Bu nh2 n ~ Bu Li
cf3 〇〆 〇 Λ 6N-HC1 CF3C02Etcf3 〇〆 〇 Λ 6N-HC1 CF3C02Et
NHNH
I Nil 〇〆 cf3 nh2 -26 本紙張尺度適用中國國家標準(CNS ) A4規格(21〇X 297公釐) 587078 /ΚΊ Β7 五、發明説明(24 流程2説明另一種製備酮-苯胺的方法,此是以合適的取代 木胺合成的’在礎化作用及胺保護作用之後,、利用強驗及 二氟乙酸乙酯將諸如三氟甲基併入結構中,去保護作用之 後可得酮-苯胺。製備酮·苯胺的他種方法熟知於技藝中, 如何比斯等人,Tetr· Lett· 1994,3 5 (3 7), 6811-6^14、,該文 獻中的内容併入本説明書中參考。 、 流程3I Nil 〇〆cf3 nh2 -26 This paper size is applicable to Chinese National Standard (CNS) A4 (21〇X 297 mm) 587078 / ΚΊ Β7 5. Description of the invention (24 Scheme 2 illustrates another method for preparing keto-aniline, This is based on the synthesis of suitable substituted lignans. After basalization and amine protection, ketones such as trifluoromethyl are incorporated into the structure using strong testing and ethyl difluoroacetate, and ketones can be obtained after deprotection- Aniline. Other methods for the preparation of ketones and anilines are well known in the art. How Bis et al., Tetr Lett 1994, 3 5 (3 7), 6811-6 ^ 14, the content of this document is incorporated into this description. Reference in the book., Flow 3
COOH HN (CH3) OCH: nh:COOH HN (CH3) OCH: nh:
con (〇cn3) ch3con (〇cn3) ch3
TrBrr DIPEA ---—-^TrBrr DIPEA ------ ^
CON(OCH3)CH3 N(H)Tr CH2C12CON (OCH3) CH3 N (H) Tr CH2C12
氧化作用oxidation
還原作用 CH〇 N(Η )Tr Q 、 CF3 N(H)Tr 經濟部中央標準局員工消費合作社印製 另一種製備2-三氟乙醯苯胺的方法列於流程3中,形成保 護性苯胺後,將醯胺還原並加成三氟甲基,用氧化劑(如氧 化鐘)進行氧化作用,即產生可用的中間物質。 流程4Reduction CH0N (Η) Tr Q, CF3 N (H) Tr Another method for preparing 2-trifluoroacetanilide by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs is listed in Scheme 3, after the formation of protective aniline , Reducing amidine and adding trifluoromethyl, and oxidizing with an oxidant (such as an oxidized bell) to produce a usable intermediate. Flow 4
R Oil a) TMSNCO DMAP/THF b) TBAF/TI^FR Oil a) TMSNCO DMAP / THF b) TBAF / TI ^ F
4八分子篩 NH sieves 〜------— 〇 〇4 Eight molecular sieves NH sieves ~ -------- 〇 〇
R1 27 587078 A7 B7 五、發明説明(25 )R1 27 587078 A7 B7 V. Description of the invention (25)
a · n-BuLi/HCCRVTHF b. BF3〇Et2 、a · n-BuLi / HCCRVTHF b. BF3〇Et2,
Pd/C R4Pd / C R4
H, S 、 (請先閱讀背面之注意事項再4-寫本頁) 利用流程4所述詳細的一般方法,吾人可製備本發明化合 物’在内含二甲基胺基吡啶之無水四氫呋喃溶液中,將流 程1及2説明方法所製備之酮-苯胺丨與異氰酸三甲基單矽 烷基酯反應’其後以氟化四丁基銨處理,如此可得羥基·尿 L,在回流甲苯或二甲苯中,用去水劑(如4 a分子篩)將羥 基-尿2_去水,可產生酮亞胺L,用綫化鋰(此是在不同的 容器中’將對應取代性块類與無水四氫吱喃中之正* 丁基鐘 反應後製備而得的)處理酮亞胺^__後,取代炔屬R2基團加 成後可得4,4_雙取代3,4-二氫-2(1氫)-,奎岭琳酮上_,此 爲式I化合物。將化合物4_之块屬键結還原(如利用氳化作 用)可產生對應之晞基(未列)或飽和化合物5。 在有/無路易士酸催化劑(如PF3)下,將亞胺2__與R2Li或 格力那試劑R2MgX直接反應可將其他的R2基團併入,參 考哈夫曼等人,J· Org· Chem· 1995,60,1590_1594,該文 -28- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐)H, S, (Please read the precautions on the back before 4-writing this page) Using the detailed general method described in Scheme 4, we can prepare the compound of the present invention in an anhydrous tetrahydrofuran solution containing dimethylaminopyridine The ketone-aniline prepared in the method described in Schemes 1 and 2 is reacted with trimethyl monosilyl isocyanate 'and then treated with tetrabutylammonium fluoride to obtain hydroxy · urine L, which is refluxed in toluene Or in xylene, dehydrate the hydroxyl-urine 2_ with a dehydrating agent (such as 4 a molecular sieve) to produce ketimine L. Use linear lithium (this is in a different container. (Prepared after reaction with n-butyl butyl bell in anhydrous tetrahydrocran). After treatment of ketimine ^ __, the addition of substituted acetylenic R2 group can obtain 4,4_disubstituted 3,4- Dihydro-2 (1hydro)-, kulinglinone, which is a compound of formula I. Reduction of the bulk bond of compound 4_ (such as by using tritiated action) can produce the corresponding fluorenyl group (not listed) or saturated compound 5. In the presence or absence of a Lewis acid catalyst (such as PF3), the direct reaction of the imine 2__ with R2Li or the Grignard reagent R2MgX can incorporate other R2 groups. Refer to Huffman et al., J. Org. Chem · 1995,60,1590_1594, this article-28- This paper size applies to China National Standard (CNS) A4 specification (210X297 mm)
、1T 經濟部中央榡準局員工消費合作社印製 587078 經濟部中央標準局員工消費合作社印製 ΑΊ -------11__— 五、發明説明(26 ) 獻内容併入本説明書參考。 在某些例子中,一種式I或Π化合物的鏡像異構物與其 他的異構物比較起來具有較佳的活性,當有需要時,藉由 HPLC利用範例27-34(流程4)中示範之對掌管柱分離消旋 物質’或是利用解離劑(諸如崁内酯酸氣,如湯姆士 j特克, 等人,J. Med· Chem· 1994,37, 2437-2444)進行解離作用來 分離消旋物質。亦可利用對掌性催化劑或是對掌性配位體 直接合成式I化合物的對掌性,如馬克(Mark) A.哈夫曼,等 人,J. Org. Chem. 1995,60,1590-1594。 以下範例中所述之具體實例可説明本發明其他的特性, 而所述之具體實例是用以説明本發明,而本發明並非侷限 於此。 範例 範例中所用之縮寫意義如下:,,,,表示攝氏溫度,” d” 表示雙次,” dd”表示兩個雙次,” eq”表示當量或是等 量,”g”表示克,”mg”表示毫克,” mL”表示毫升,” H” 表示氫,’’hr”表示小時,,,m”表示多次,”M”表示莫 耳,’’min”表示分鐘,’’MHz”表示百萬赫茲,” MS”表示質 譜儀,”nmr”或”NMR”表示核磁共振質譜儀,” t”表示三 次,”TLC”表示薄層層析法,”EDAC”表示1_(3·二曱基胺 基丙基)-3 -乙基碳亞胺氫氣酸鹽,” DIPEA”表示二異丙基 乙胺,,’TBAF”表示氟化四丁基胺,”LAH”表示氫化鋰鋁, 而’’TEA”表示三乙胺。 範例1 -29 - 本紙張尺度適用中國國家標準(CNS ) Α4規格(210Χ 297公釐) — (請先閲讀背面之注意事項再填寫本頁) 、1Τ 587078 A7 B7 五、發明説明(27 ) 製備(+ /- )_6·氣_4_環丙基乙決基-4_三氟甲基_3,4_二氣 _2 (1氫)-4峡淋酮(r4 =環丙基) 、, 1T Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs 587078 Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economics. In some examples, the mirror image isomer of a compound of formula I or Π has better activity than other isomers. When necessary, it is demonstrated by HPLC using Examples 27-34 (Scheme 4) The separation of racemic materials on the stem column 'or using a dissociating agent (such as galactone acid gas, such as Thomas J Turke, et al., J. Med. Chem. 1994, 37, 2437-2444) to dissociate Separation of racemic material. It is also possible to synthesize the palmity of compounds of formula I directly using palmity catalysts or palmate ligands, such as Mark A. Huffman, et al., J. Org. Chem. 1995, 60, 1590 -1594. The specific examples described in the following examples can illustrate other characteristics of the present invention, and the specific examples described are used to illustrate the present invention, and the present invention is not limited thereto. The meanings of the abbreviations used in the examples are as follows: ,,,, means Celsius, "d" means double, "dd" means two doubles, "eq" means equivalent or equivalent, "g" means gram, " “mg” means milligram, “mL” means milliliter, “H” means hydrogen, “hr” means hour, and “m” means multiple times, “M” means mole, “min” means minute, and “MHz” Means millions of hertz, "MS" means mass spectrometer, "nmr" or "NMR" means nuclear magnetic resonance mass spectrometer, "t" means three times, "TLC" means thin layer chromatography, and "EDAC" means 1_ (3.2 Fluorenylaminopropyl) -3 -ethylcarbodiimide hydrochloride, "DIPEA" means diisopropylethylamine, "TBAF" means tetrabutylamine fluoride, "LAH" means lithium aluminum hydride, And "TEA" means triethylamine. Example 1 -29-This paper size applies Chinese National Standard (CNS) A4 specification (210 × 297 mm) — (Please read the precautions on the back before filling this page), 1T 587078 A7 B7 V. Description of the invention (27) Preparation (+ /-) _6 · qi_4_cyclopropylethoxy-4_trifluoromethyl_3,4_digas_2 (1 hydrogen) -4 isorone (r4 = cyclopropyl),
cf3 I 一 fcf3 I a f
a) THSNCO ΟΜΛΡ/THF b) TBAF/TIIFa) THSNCO ΟΜΛΡ / THF b) TBAF / TIIF
Phcil3 Ti 、mol、分予篩 R4Phcil3 Ti, mol, fractionation sieve R4
ΙΙΙ-ίΙΙΙ-ί
•O• O
--------4! (請先閱讀背面之注意事項再餐寫本頁} 步驟1、以I_a合成II-a 將二甲基胺基吡啶(0.25克,2.02毫莫耳)及異氰酸三甲 基單碎燒基酯(6.05克,7.11毫升,52.5毫莫耳)加至内含 式I-a化合物(4.5 5g,20.2毫莫耳)之無水THF (40毫升) 溶液中,室溫下攪拌混合物約16小時、,而後再加入氟化四 丁基銨(溶於THF中,1 Μ溶液,2 1毫升),用另外之THF (2 0耄升)稀釋粘稠的混合物,並在室溫下攪拌〇 5小時, 減壓下去除THF,將殘餘物重_溶解於EtOAc (100毫升) 中’並依序以1 N HC1 (70毫升),飽和NaHC03 (70毫升) 水溶液與飽和NaCl水溶液(50毫升)清洗,以MgS〇4乾燥 有機相,過濾並在減壓下濃縮濾液,如此可產生淡黃色固 悲物質,用己烷磨碎固態物去除黃顏色後可得白色固態狀 之 Ila (5.09 克,94%) : 4 NMR (300MHz,丙酮-d6) d ^1. 經濟部中央標準局員工消費合作社印製 -30- 經濟部中央標準局員工消費合作社印製 587078 A7 B7 五、發明説明(28 ) 9.06 (br s,1H),7.48 (s,1H),7.40(br s,1H),7.34 (dd,-------- 4! (Please read the notes on the back before writing this page) Step 1. Synthesis of II-a from I_a Dimethylaminopyridine (0.25 g, 2.02 mmol) and Trimethyl isocyanate (6.05 g, 7.11 ml, 52.5 mmol) was added to a solution of anhydrous THF (40 ml) containing a compound of formula Ia (4.5 5 g, 20.2 mmol), and The mixture was stirred for about 16 hours at room temperature, then tetrabutylammonium fluoride (dissolved in THF, 1 M solution, 21 ml) was added, the viscous mixture was diluted with additional THF (20 ml), and Stir at room temperature for 0.5 hours, remove the THF under reduced pressure, and dissolve the residue in EtOAc (100 mL), and then sequentially with 1 N HC1 (70 mL), saturated NaHC03 (70 mL) aqueous solution and saturated NaCl aqueous solution (50 ml) was washed, and the organic phase was dried with MgSO4, filtered and the filtrate was concentrated under reduced pressure, so as to produce a pale yellow solid substance. The solid was triturated with hexane to remove the yellow color to obtain a white solid. Ila (5.09 g, 94%): 4 NMR (300 MHz, acetone-d6) d ^ 1. Printed by the Consumers' Cooperative of the Central Standards Bureau, Ministry of Economic Affairs-30- Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 587078 A7 B7 V. Description of Invention (28) 9.06 (br s, 1H), 7.48 (s, 1H), 7.40 (br s, 1H), 7.34 (dd,
J=8.8,2·6Ηζ,1H),6.97 (d,J=8.8Hz, 1H) ; 19F NMR (282MHz,丙酮 d-6) d -86.33,-86.35 ; IR (KBr 沉殿 物)1 724, 1 678,1 3 98,1198,1174 cm1 ; MS (Cl) m/e266 (MH+100) 〇 步驟2、以ΙΙ-a合成III-a 内含分子篩(大約100毫克)之ΙΙ-a (5·09克,19.1亳莫耳) 甲苯(1 5 0毫升)懸浮液加熱回流1 6小時,將所得之黃色澄 清溶液冷卻至室溫,並將沉澱固態物溶解於丙酮中,用眞 空過濾法去除分篩,在減壓下濃縮濾液,以己烷磨碎後, 可得黃色固態物 ΙΙΙ-a (4·25 克,89%) : 4 NMR (300 MHz 丙酮-d6)d 7.86-7.82 (m,2H),7.61 (d,J=8.8Hz,1H) ; % NMR (282 MHz 丙酮-d6)d-67.88。 步驟3、以Ilia合成iv-a 將内含環丙基乙炔(13·0毫升之30重量百分比甲苯/Thf/ 己燒溶液,59.0毫莫耳)之無水THF(118毫升)溶液冷卻至 78 C ’再以正- BuLi (32.8毫升1.6M之己烷溶液,52.4毫 莫耳)處理,置於冰浴中將溫度回升至0 t,靜置〇 5小 ^ ° 在 -78 °C下,將炔化鋰加至内含III-a (3 12克,a 6毫莫耳) 之操水THF (6 6毫升)溶液中(添加時間大約超過1 〇分 鐘),其後加入 boron trifluoride etherate (0.89 克,0.80 毫 升,6.28耄莫耳),移除冰浴。讓反應回溫至室溫,在室 溫下攪拌4小時,再以1M檸檬酸(100毫升)終止反應。在 (請先閱讀背面之注意事項再填寫本頁) -.J = 8.8, 2 · 6Ηζ, 1H), 6.97 (d, J = 8.8Hz, 1H); 19F NMR (282MHz, acetone d-6) d -86.33, -86.35; IR (KBr Shen Dianwu) 1 724, 1 678, 1 3 98, 1198, 1174 cm1; MS (Cl) m / e266 (MH + 100) 〇 Step 2. Synthesis of III-a from ΙΙ-a III-a containing molecular sieve (about 100 mg) (5 · 09 g, 19.1 mol) Toluene (150 ml) suspension was heated under reflux for 16 hours, the resulting yellow clear solution was cooled to room temperature, and the precipitated solid was dissolved in acetone and removed by air filtration It was sieved, and the filtrate was concentrated under reduced pressure, and triturated with hexane to obtain III-a (4.25 g, 89%) as a yellow solid: 4 NMR (300 MHz acetone-d6) d 7.86-7.82 (m , 2H), 7.61 (d, J = 8.8Hz, 1H);% NMR (282 MHz acetone-d6) d-67.88. Step 3. Synthesize iv-a with Ilia. Cool the solution containing cyclopropylacetylene (13.0 ml of 30% by weight toluene / Thf / hexane solution, 59.0 mmol) in anhydrous THF (118 ml) to 78 C. 'Re-treatment with n-BuLi (32.8 ml of a 1.6M hexane solution, 52.4 mmol), put the temperature back to 0 t in an ice bath, and let it stand for 0 5 hours at -78 ° C. Lithium acetylide was added to a solution of III-a (3 12 g, a 6 mM) in THF (66 ml) (addition time was approximately 10 minutes), and then boron trifluoride etherate (0.89 G, 0.80 ml, 6.28 mol), remove the ice bath. The reaction was allowed to warm to room temperature, stirred at room temperature for 4 hours, and then stopped with 1M citric acid (100 ml). In (Please read the notes on the back before filling out this page)-.
、1T 31 - 587078 A7 B7 五、發明説明(29 ) 減壓下濃縮混合物至原體積的1/2 ,用EtOAc (200毫升) 稀釋,去除水相,依序以飽和的NaHC03水溶液(100毫升) 及飽和的NaCl水溶液(100毫升)清洗,以MgS04乾燥有機1T 31-587078 A7 B7 V. Description of the invention (29) The mixture was concentrated under reduced pressure to 1/2 of the original volume, diluted with EtOAc (200 ml), the aqueous phase was removed, and a saturated NaHC03 aqueous solution (100 ml) was sequentially used. And saturated NaCl aqueous solution (100 ml), and dried with MgS04 organic
JT 相,過濾並在減壓下濃縮濾液,利用閃火層析法(3% MeOH/CH2Cl2)純化粗物質後,可得深黃色油狀物,以此可 得白色固態結晶IV-a (R4 =環丙基)(3.85克,97%) : m· ρ· 86.6-88 °C ; !H NMR (300MHz,丙酮8.95 (br s,1H), 7·51 (br s,1Η),7·43 (br s,1Η),7.40 (dd,J=8.8,2·4Ηζ, 1H),7.02 (d,J=8.8Hz,1H),1.49-1.41 (m,1H),0.93-0.82 (m,1H),0.77-0.74 (m,1H) ; 19F NMR (282MHz 丙酮-d6)d -82.96 ; IR (KBr 沉澱物)1696,1172 cm-1; C14H10ClF3N2O 所得之 MS (CI)m/e : 315.051201,發現 315.051626 ; 315 (MH+,51),332 (M+NH4+,100);計算分析 C14H10N2ClF3O. 〇.25H20 : C,52.68 ; H,3.32 ; N,8.78 ;發現:C, 52.61 ; H,3.35 ; N, 8.28 〇 範例2 製備(+ /-)-6 -氯-4-異丙基乙炔基-4-三氟甲基-3,4·二氫 •2(1氫)-喹唑啉酮(R4 =異丙基) 經濟部中央標準局員工消費合作社印製 (請先閲讀背面之注*事項再療寫本頁) 根據範例1步驟3的方法,以衍生自3 -甲基-1 - 丁块(6 2 毫克,93毫升,0.905毫莫耳)之块化鋰處理nl-a (50毫 克,0.201毫莫耳)溶液,利用閃火層析法(35〇/〇 EtOAc/己 烷)純化所得粗製物質後,可產生26毫克(41%)所要的產 物:1h NMR (300 MHzH 9.08 (br s,lH),7.59 (br s, 1H), 7.53 (br s,1H),7.40 (dd,J=8.4,2.2Hz,1H),7.02 (d, -32- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 587078 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明(30 ) J=8.8Hz,1H),2·81 — 2.68 (m,1H),1.20 (dd,J=6.6Hz, 6H) ; 19F NMR (282MHz 丙酮-d6) Θ -83.05 ; C14H12C1F3N20 計算所得 MS (CI)m/e : 317.066851,發現 317.069433 ; 317(MH+,43),334(M+NH4+,100)。 範例3 製備( + /_)_6 -氣- 4- (2 -冲b淀基)乙块基-4·-三氟甲基-3,4-二氫- 2(1氫)-p奎峻琳酮(r4 = p比淀基) 根據範例1步驟3的方法,以衍生自2 乙炔基吡啶(0· 19 克,1.81毫莫耳)之块化鋰處理m-a (1〇〇毫克,0.402毫 莫耳)溶液,利用HPLC (2.5% MeOH/CH2Cl2)純化所得之 粗製物質後,可得85毫克(60%)所要的產物:mp 105 °C ; 4 NMR (300 MHz,丙酮-d6)e 9.14 (br s,1H),8.64-8.61 (m,1H),7.89-7.84 (m,2H),7.70-7.66 (m,2Η),7·48-7·43 (m,2H),7.09 (d,J=8.8Hz,1H) ; 19F NMR(282MHz 丙酮-d6) ^ -82.48 ; IR (KBr 沉澱物)1704,1430,1186 cm·1 ; C16H10ClF3N3O 計算所得之 MS (CI)m/e : 352.046450,發 現 352.046956 ; 352 (MH+,100);計算分析 C16H9C1F3N30· 0.125 H20 : C,54.3 ; H,2.56 ; N,11.9 ;發現:C, 54.71 ; H, 3.03 ; N, 11.3 。 範例4 製備( + /·)·6-氣·4·乙基乙炔基·4_三氟甲基·3,4-二氫_ 2(1氫奎峻ρ林酮(r4 =乙基) 根據範例1步驟3的方法,以衍生自1-丁炔(109毫克, 2.01毫莫耳)之炔化鋰處理ιπ-a (1〇〇毫克,0.402毫莫耳) -33- 本紙張尺度適用中國國家標準(CNS ) A4規格(21〇X 297公釐) (請先閲讀背面之注意-事項再瘡寫本頁) 、1Τ 587078 A7 B7 五、發明説明(31 ) 溶液,利用HPLC (2.5% MeOH/CH2Cl2)純化所得之粗製物 質後,可得79毫克(65%)所要的產物:b NMR (300MHz 丙酮-d6)d 9.05 (br s,1H), 7.54 (br s, 2H),7.41-7.39 (m, 1H),7.02(d, J=8.4Hz,1H),2.36-2.32 (m, 2H),2.18-1.13 (m, 3H) : 19F NMR (282MHz 丙酮-d6) d -82.99 ; C13H1()C1F3N20 計算所得之 MS(CI)m/e : 303.051201,發 現 303.051882 ; 303 (MH+,55),320(M+NH4+,100)。 範例5 製備( + /-)-6-氣-4·苯基乙炔基-4_三氟甲基-3,4·二氫· 2(1氫)-喹唑啉酮(R4=苯基)JT phase, filtration and concentration of the filtrate under reduced pressure. After purification of the crude material by flash chromatography (3% MeOH / CH2Cl2), a dark yellow oil was obtained, whereby white solid crystal IV-a (R4 = Cyclopropyl) (3.85 g, 97%): m · ρ · 86.6-88 ° C;! H NMR (300 MHz, acetone 8.95 (br s, 1H), 7.51 (br s, 1Η), 7 · 43 (br s, 1Η), 7.40 (dd, J = 8.8, 2.4Ηζ, 1H), 7.02 (d, J = 8.8Hz, 1H), 1.49-1.41 (m, 1H), 0.93-0.82 (m, 1H), 0.77-0.74 (m, 1H); 19F NMR (282MHz acetone-d6) d -82.96; IR (KBr precipitate) 1696, 1172 cm-1; MS (CI) m / e from C14H10ClF3N2O: 315.051201, Found 315.051626; 315 (MH +, 51), 332 (M + NH4 +, 100); calculated and analyzed C14H10N2ClF3O. 0.25H20: C, 52.68; H, 3.32; N, 8.78; found: C, 52.61; H, 3.35; N , 8.28 〇 Example 2 Preparation of (+/-)-6-chloro-4-isopropylethynyl-4-trifluoromethyl-3,4 · dihydro • 2 (1hydro) -quinazolinone (R4 = Isopropyl) Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs (please read the note on the back * Matters before writing this page). Lithium-treated nl-a (50 mg, 0.201 mmol) solution from 3-methyl-1 -butanium block (62 mg, 93 ml, 0.905 mmol), using flash chromatography ( After purification of the obtained crude material (35.0 / 0 EtOAc / hexane), 26 mg (41%) of the desired product was produced: 1h NMR (300 MHzH 9.08 (br s, 1H), 7.59 (br s, 1H), 7.53 ( br s, 1H), 7.40 (dd, J = 8.4, 2.2Hz, 1H), 7.02 (d, -32-) This paper size applies to China National Standard (CNS) A4 (210X297 mm) 587078 Central Bureau of Standards, Ministry of Economic Affairs Printed by employees' consumer cooperatives A7 B7 V. Description of invention (30) J = 8.8Hz, 1H), 2.81 — 2.68 (m, 1H), 1.20 (dd, J = 6.6Hz, 6H); 19F NMR (282MHz acetone -d6) Θ -83.05; C14H12C1F3N20 calculated MS (CI) m / e: 317.066851, found 317.069433; 317 (MH +, 43), 334 (M + NH4 +, 100). Example 3 Preparation of (+ / _) _ 6 -Gas-4- (2 -b-b-based) Ethyl-4 · -trifluoromethyl-3,4-dihydro-2 (1 hydrogen) -p Kui Jun Linone (r4 = p ratio) Based on the method in step 3 of Example 1, treated with lithium aluminized ma (100 mg, 0.402 mmol) derived from 2 ethynylpyridine (0.19 g, 1.81 mmol) Mol) solution, and the crude material obtained was purified by HPLC (2.5% MeOH / CH2Cl2) to obtain 85 mg (60%) of the desired product: mp 105 ° C; 4 NMR (300 MHz, acetone-d6) e 9.14 (br s, 1H), 8.64-8.61 (m, 1H), 7.89-7.84 (m, 2H), 7.70-7.66 (m, 2Η), 7.48-7 · 43 (m, 2H), 7.09 (d , J = 8.8Hz, 1H); 19F NMR (282MHz acetone-d6) ^ -82.48; IR (KBr precipitate) 1704, 1430, 1186 cm · 1; C16H10ClF3N3O MS (CI) m / e: 352.046450, Found 352.046956; 352 (MH +, 100); Computational analysis C16H9C1F3N30 · 0.125 H20: C, 54.3; H, 2.56; N, 11.9; Found: C, 54.71; H, 3.03; N, 11.3. Example 4 Preparation (+ / ·) · 6-Gas · 4 · Ethylethynyl · 4-trifluoromethyl · 3,4-dihydro_2 (1 Hydroquinone ρ Linone (r4 = ethyl) according to Method of Step 3 of Example 1 to treat ιπ-a (100 mg, 0.402 mmol) with lithium acetylide derived from 1-butyne (109 mg, 2.01 mmol) -33- This paper is for China National Standard (CNS) A4 specification (21〇X 297mm) (Please read the note on the back-matters before writing this page), 1T 587078 A7 B7 V. Description of the invention (31) Solution, using HPLC (2.5% MeOH / CH2Cl2) After purification of the obtained crude material, 79 mg (65%) of the desired product can be obtained: b NMR (300 MHz acetone-d6) d 9.05 (br s, 1H), 7.54 (br s, 2H), 7.41-7.39 (m, 1H), 7.02 (d, J = 8.4Hz, 1H), 2.36-2.32 (m, 2H), 2.18-1.13 (m, 3H): 19F NMR (282MHz acetone-d6) d -82.99; C13H1 ( ) MS (CI) m / e calculated by C1F3N20: 303.051201, found 303.0051882; 303 (MH +, 55), 320 (M + NH4 +, 100). Example 5 Preparation of (+ /-)-6-Ga-4 · benzene Ethynyl-4_trifluoromethyl-3,4 · dihydro · 2 (1hydro) -quinazolinone (R4 = phenyl)
根據範例1步驟3的方法,以衍生自苯基乙炔(185毫 克,1.81毫莫耳)之块化鋰處理III_a (100毫克,0.402毫 莫耳)溶液,利用HPLC (2.5% MeOH/CH2Cl2)純化所得之 粗製物質後,可得54毫克(38%)所要的產物:4 NMR (300 MHz 丙酮-d6)d 9.07 (br s,1H),7.74 (br s,1H),7.67 (br s,1H), 7.62-7.58 (m,2H),7·48_7·40 (m,4H),7.08 (d, J=8.4Hz,1H) ; 19F NMR (282 MHz 丙酮-d6) β-82.67 ; IR 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) (反31*沉澱物)1696,1186〇111-1;(:171111(:1?3]^20計算所得之 MS (CI)m/e : 351.051201 ,發現 351.051704 ; 351 (MH+,51),368 (M+NH4+,100);計算分析 Ci7H10ClF3N2O · 0.25H2O : C, 57.48 ; H, 2.98 ; N, 7.89 ;發現:C, 57.00 : H, 3.03 ; N,7.48 〇 範例6 製備( + /·)_4·環丙基乙块基-6 -甲氧基-4-三氟甲基-3,4- -34- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 587078 A7 B7 五、發明説明(32 ) 二氫-2 (1氫)-邊唑琳酮(R 4 =環丙基)A solution of III_a (100 mg, 0.402 mmol) from phenylacetylene (185 mg, 1.81 mmol) was treated according to the method of Step 3 in Example 1, and purified by HPLC (2.5% MeOH / CH2Cl2) After the obtained crude material, 54 mg (38%) of the desired product was obtained: 4 NMR (300 MHz acetone-d6) d 9.07 (br s, 1H), 7.74 (br s, 1H), 7.67 (br s, 1H ), 7.62-7.58 (m, 2H), 7.48_7 · 40 (m, 4H), 7.08 (d, J = 8.4Hz, 1H); 19F NMR (282 MHz acetone-d6) β-82.67; IR Ministry of Economy Printed by the Consumer Standards Cooperative of the Central Bureau of Standards (please read the precautions on the back before filling this page) (anti-31 * sediment) 1696, 1186〇111-1; (: 171111 (: 1? 3) ^ 20 Calculated MS (CI) m / e: 351.051201, found 351.051704; 351 (MH +, 51), 368 (M + NH4 +, 100); calculated and analyzed Ci7H10ClF3N2O · 0.25H2O: C, 57.48; H, 2.98; N, 7.89; found: C, 57.00: H, 3.03; N, 7.48. Example 6 Preparation of (+ / ·) -4 · cyclopropylethyl-6-methoxy-4-trifluoromethyl-3,4- -34-benzyl Paper size applies to China National Standard (CNS) A4 specification (210X297 mm) 587078 A7 B7 V. Description of the invention (32) Dihydro-2 (1 hydrogen) -zozolone (R 4 = cyclopropyl)
(請先閲讀背面之注意事項再填寫本頁) 經濟部中央標準局員工消費合作社印製 步驟1、自V-a合成VI-a(Please read the notes on the back before filling this page) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economy
以範例1步驟1中所述的方法’用二甲基胺基吡啶及異 氰酸三甲基單矽烷基酯處理V-a (0.50克,2.28毫荚耳)溶 液後,可得0.58克(97%)所要的產物:4 NMR (300MHz 丙酮-d6)d 8·81 (br s,1H),7.17 (br s,1H),7.11 (br s,1H), 7.00-6.92 (m,2H),6.83 (s,1H),3.76 (s,3H) ; 19F NMR (282 MHz 丙酮-d6)d-85.99。 步驟2、自vi-a合成Vll_a 如範例1步驟2中所述之方法,將VI _ a ( 0 · 5 8克,2 · 21 毫莫耳)溶液在甲苯中加熱回流後,可得〇·5〇克(93%)所要 的產物:^ NMR (300 MHz 丙酮-d6) β 7.52 (br s,2H), 7.27 (s,1H),3.90 (s, 3H) ; 19F NMR (282 MHz 丙酬-d6)d -68.08 〇 步驟3、自VII-a合成VIn-a -35 - 本紙張尺度適用中國國家標準(CNS ) M規格(210X297公釐) 587078 A7 B7 五、發明説明(33 ) 根據範例1步驟3的方法,以衍生自環丙基乙炔(0.41毫 升之30%重量百分比曱苯/THF/乙块,1.85毫莫耳)之炔化 鋰處理VII-a (100毫克,0.410毫莫耳)溶液,利用HPLC (2.5% MeOH/CH2Cl2)純化所得之粗製物質後,可得1〇3毫 克(81%)所要的產物:iNMRpOOMHz 丙酮-d6)ci 8.77 (br s,1H),7.29 (br s,1H),7.06 (br s, 1H),6.99-6.90 (m,2H),3.77 (m,3H),1.46-1.38 (m, 1Η),0.91-0.85 (m,2H), 0.79-0.72 (m,2H) ; 19F NMR (282 MHz 丙酮-d6)ci-82.61 ; C15H14C1F3N202 計算所得之 MS(CI)m/e : 311.100738,發 現 311.099970 ; 311(MH+,100)。 範例7 製備( + /_)-4_異丙基乙炔基-6_曱氧基-4-三氟甲基_3,4-二氳_2(1氫)·喹唑啉酮(R4 =異丙基) 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) 根據範例1步驟3的方法,以衍生自3-曱基_1-丁块(126 毫克,0.19毫升,1.85毫莫耳)之块化鋰處理VII_a (100 毫克,0.410毫莫耳)溶液,利用閃火層析法(2.5% MeOH/CH2Cl2)純化所得粗製物質後,可產生3 0毫克(24%) 所要的產物:mp 228-229 °C; 1HNMR (300 MHz) d 8.72 (br s, 1H), 7.27 (br s, 1H), 7.10 (br s, 1H), 7.00-6.91 (m, 2H),3.77 (s,3H),2.73-2.67 (m,1H),1.20 (dd,J=7·0,丄·5 Hz,6H) ; 19F NMR (282 MHz 丙酮-d6) β -82.71 ; IR (KBr 沉澱物)1696,1428,1190,1176 cm-1 ; C15H16C1F3N202 計 算所得 MS (Cl) m/e : 313.1 16388,發現 3 13.1 15871 ; 313 (MH+,100),330 (M+NH4+,15); C15H15F3N202 計算分析:C, -36 - 本紙張尺度適用中國國家標準(CNS ) A4規格(21GX297公釐) 587078 A7 B7 五、發明説明(35 ) 溶液,利用閃火層析法(2.5% MeOH/CHbCh)純化所得粗製 物質後,可產生3 4毫克(24%)所要的產物:' mp 206.2-207.7 °C ; 4 NMR (300 MHz 丙酮-d6) d 8.85 (br s, 1H), 7.60-7.57 (m,3H),7.49-7.39 (m,3H), 7·21 (br s,1H), 7·05·6·96 (m, 2H),3.79 (s, 3H) ; 19F NMR (282 MH、z,丙酮 -d6)d-82.32 ; IR (KBr 沉澱物)1696,1516,1430,12s36, 1204,1184,1128 cm·1 ; C18H14F3N202 計算所得 MS (Cl) m/e : 347.100738,發現 347.101482 ; 347(MH+,100), 364(M+NH4+,48) ; C18H13F3N2〇2 計算分析:C,62.43 ; Ή, 3.78 ; N, 8.10 ;發現:C,62·35 ; Η; 3.58 ; N, 7.83。 範例10 製備( + /-)-4-環丙基乙块基_5,6-二氟-4-三氟甲基-3,4-二氫- 2(1氫)·4峻淋酮(R4 =環丙基) (讀先閱讀背面之注意事項再填寫本頁} "口After treating Va (0.50 g, 2.28 millipods) solution with dimethylaminopyridine and trimethyl monosilyl isocyanate by the method described in Example 1, Step 1, 0.58 g (97%) was obtained. ) Desired product: 4 NMR (300MHz acetone-d6) d 8.81 (br s, 1H), 7.17 (br s, 1H), 7.11 (br s, 1H), 7.00-6.92 (m, 2H), 6.83 (s, 1H), 3.76 (s, 3H); 19F NMR (282 MHz acetone-d6) d-85.99. Step 2. Synthesis of Vll_a from vi-a According to the method described in step 2 of Example 1, the solution of VI_a (0.58 g, 2.21 mmol) was heated under reflux in toluene to obtain 〇 ·. 50 g (93%) of the desired product: NMR (300 MHz acetone-d6) β 7.52 (br s, 2H), 7.27 (s, 1H), 3.90 (s, 3H); 19F NMR (282 MHz propane) -d6) d -68.08 〇 Step 3. Synthesize VIn-a -35 from VII-a-This paper size applies Chinese National Standard (CNS) M specification (210X297 mm) 587078 A7 B7 V. Description of the invention (33) According to the example 1 The method of step 3, treating VII-a (100 mg, 0.410 mmol) with lithium acetylide derived from cyclopropylacetylene (30% by weight of toluene / THF / ethyl block, 1.85 mmol) ) Solution, the crude material obtained was purified by HPLC (2.5% MeOH / CH2Cl2) to obtain 103 mg (81%) of the desired product: iNMRpOOMHz acetone-d6) ci 8.77 (br s, 1H), 7.29 (br s, 1H), 7.06 (br s, 1H), 6.99-6.90 (m, 2H), 3.77 (m, 3H), 1.46-1.38 (m, 1Η), 0.91-0.85 (m, 2H), 0.79-0.72 (m, 2H); 19F NMR (282 MHz acetone-d6) ci-82.61; C15H14C1F3N202 calculation The obtained MS (CI) m / e: 311.100738, found 311.099970; 311 (MH +, 100). Example 7 Preparation of (+ / _)-4_isopropylethynyl-6_fluorenyloxy-4-trifluoromethyl_3,4-difluorenyl_2 (1hydro) · quinazolinone (R4 = Isopropyl) 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 this page), according to the method in step 1 of Example 1, derived from 3-fluorenyl_1-butyl block (126 mg , 0.19 ml, 1.85 mmoles) of lithium VII_a (100 mg, 0.410 mmoles) solution, purified by flash chromatography (2.5% MeOH / CH2Cl2) to produce 30 mg (24%) Desired product: mp 228-229 ° C; 1HNMR (300 MHz) d 8.72 (br s, 1H), 7.27 (br s, 1H), 7.10 (br s, 1H), 7.00-6.91 (m , 2H), 3.77 (s, 3H), 2.73-2.67 (m, 1H), 1.20 (dd, J = 7 · 0, 丄 · 5 Hz, 6H); 19F NMR (282 MHz acetone-d6) β -82.71 ; IR (KBr precipitate) 1696, 1428, 1190, 1176 cm-1; Calculated MS (Cl) m / e: 313.1 16388, C15H16C1F3N202, found 3 13.1 15871; 313 (MH +, 100), 330 (M + NH4 +, 15); C15H15F3N202 Calculation analysis: C, -36-This paper size is applicable to China National Standard (CNS) A4 specification (2 1GX297 mm) 587078 A7 B7 V. Description of the invention (35) The crude material obtained after purification by flash chromatography (2.5% MeOH / CHbCh) can produce 34 mg (24%) of the desired product: 'mp 206.2-207.7 ° C; 4 NMR (300 MHz acetone-d6) d 8.85 (br s, 1H), 7.60-7.57 (m, 3H), 7.49-7.39 (m, 3H), 7.21 (br s, 1H ), 7 · 05 · 6 · 96 (m, 2H), 3.79 (s, 3H); 19F NMR (282 MH, z, acetone-d6) d-82.32; IR (KBr precipitate) 1696, 1516, 1430, 12s36, 1204, 1184, 1128 cm · 1; C18H14F3N202 Calculated MS (Cl) m / e: 347.100738, found 347.101482; 347 (MH +, 100), 364 (M + NH4 +, 48); C18H13F3N2 02 Calculation analysis: C , 62.43; Ή, 3.78; N, 8.10; found: C, 62 · 35; Η; 3.58; N, 7.83. Example 10 Preparation of (+ /-)-4-cyclopropylethyl block_5,6-difluoro-4-trifluoromethyl-3,4-dihydro-2 (1 hydrogen) · 4 Junlinone ( R4 = Cyclopropyl) (Read the precautions on the back before filling out this page} " 口
IX-aIX-a
^1. 經濟部中央標準局員工消費合作社印製^ 1. Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs
:i.o rvi/r Η 2 (1 a 丨:m) EtOII/l-l:0Ac 〆 Nil: i.o rvi / r Η 2 (1 a 丨: m) EtOII / l-l: 0Ac 〆 Nil
XIII -38 - 本紙張尺度適用中國國家標準(CNS ) A4規格(210X 297公釐) 587078 A7 B7 五、發明説明(36 ) 步驟1、自IX-a合成X-a 利用範例1步驟1所述之方法,以二甲基胺基吡啶及異 氰酸三甲基單矽烷基酯處理IX_a (6.46克,28.7毫莫耳)溶 液,後,可得6.74克(88%)所要的產物:4 NMR (300 MHz,丙酮-d6)e 9.13 (br s,1H),7.45-7.32 (m,2H), 7.18 (br s,1H),6.85-6.80 (m, 1H) ; 19F NMR (282 MHz 丙酮-d6) d -86.6 (d, 17·2,3),-137.52-137.68 (m,1), 148.47- 148.59 (m,1) 〇 步驟2、自X-a合成Xl-a 如範例1步驟2中所述之方法(二甲苯取代甲苯),將Χία (6.74 克, 25.1 毫莫耳) 溶液在二甲苯 中加熱 回流後 ,可 得6.3克(100%)所要的產物:4 NMR (300 MHz,丙酮-d6) ά 7.92-7.83 (m, 1H), 7.46-7.44 (m, 1H) ; 19F NMR (282 MHz,丙酮-d6)d -70.7 (d,38.7, 3),-136.72 (s,1),-146.47-146.57 (m, 1) 〇 步驟3、以XI_a合成XII-a 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) 根據範例1步驟3的方法,以衍生自環丙基乙炔(24.9毫 升之30%重量百分比甲苯/THF/己烷,0.113莫耳)之块化 鋰處理XI_a (6.28克,25.1毫莫耳)溶液,所得粗製黃色油 狀物質溶解於丙酮中,並在減壓下濃縮後,可產生黃色固 態物質,自丙酮中結晶後可產生5.98克(75%)所要之產 物·· mp 86.5-88.5 °C ; 4 NMR (300 MHz,丙酮-d6)d 9.01 (br s,1H),7.46 (br s,1H),7.44-7.35 (m,1H),6·86·6·81 (m, 1H), 1.41-1.37 (m,1H),0.90-0.83 (m,1H),0.74-0.69 (m, -39- 本紙張尺度適用中國國家標準(CNS ) A4規格(21 OX 297公釐) "一 ' 587078 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明(37 ) 1H) ; 19F NMR (282 MHz,丙酮-d6)d -83.3 (d,J=12.9, 1), -136.04-136.23 (m,1),-148.14-148.26 (m,1) ; IR (KBr 沉 澱物)1706, 1516,1442, 1246,1214,1196 cnT1 ; C14H1()F5N20 計算所得之 MS (Cl) m/e : 317.071329,發現 317.070836 ; 317 (MH+,100),334(M+NH4+,62);計算分 析 C14H9F5N20 : C,53.17 ; H,2·88 ; N, 8.87 ;發現·· C, 53.30 ; H, 3.16 ; N, 8.53 〇 範例1 1 製備( + /-)-5,6·二氟_4·異丙基乙炔基-4_三氟甲基-3,4-二氫(1氫)-喹唑啉酮(R4=異丙基) 根據範例1步驟3的方法,以衍生自3 -甲基-1 - 丁块 (8.87克,13.3毫升,0.130莫耳)之炔化鋰處理XI-a (7.24 克’ 2 8 · 9愛莫耳)溶液’利用閃火層析法(2 · 5 % MeOH/CH2Cl2)純化所得粗製物質後,可得黃色油狀物質, 自丙酮結晶後可產生6.77克(74%)所要的產物:mp 79-80 Ό ; 4 NMR (300 MHz 丙酮-d6)d 9.02 (br s,1H),7.50 (br s, 1H),7.44-7.35 (m,1H),6.87-6.82 (m,1H),2.69-2.65 (m, 1H), 1.17 (dd,J=7.0 Hz, 6H) ; 19F NMR (282 MHz,丙酮-d6) d-83.4(d,J=12.9,l),135.79-135.94 (m,l),-148.14- 148.26 (m,1) ; C14H12F5N20 計算所得 MS (Cl) m/e ·· 319.086979 ,發現 319.087376 ; 319(MH+,l〇〇), 336(M+NH4+,76) 〇 範例12 製備( + /)-5,6_二氟·4-(2_吡啶基)乙炔基_4-三氟甲基- -40- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X 297公釐) (請先閱讀背面之注意事項再4-寫本頁)XIII -38-This paper size applies Chinese National Standard (CNS) A4 specification (210X 297 mm) 587078 A7 B7 V. Description of the invention (36) Step 1. Synthesis of Xa from IX-a Use the method described in Example 1 Step 1 The solution of IX_a (6.46 g, 28.7 mmol) was treated with dimethylaminopyridine and trimethyl monosilyl isocyanate to obtain 6.74 g (88%) of the desired product: 4 NMR (300 MHz, acetone-d6) e 9.13 (br s, 1H), 7.45-7.32 (m, 2H), 7.18 (br s, 1H), 6.85-6.80 (m, 1H); 19F NMR (282 MHz acetone-d6) d -86.6 (d, 17 · 2, 3), -137.52-137.68 (m, 1), 148.47- 148.59 (m, 1) 〇 Step 2, Synthesize Xl-a from Xa as described in Step 2 of Example 1 Method (xylene instead of toluene), the solution of Xία (6.74 g, 25.1 mmol) was heated under reflux in xylene to obtain 6.3 g (100%) of the desired product: 4 NMR (300 MHz, acetone-d6) ά 7.92-7.83 (m, 1H), 7.46-7.44 (m, 1H); 19F NMR (282 MHz, acetone-d6) d -70.7 (d, 38.7, 3), -136.72 (s, 1), -146.47 -146.57 (m, 1) 〇 Step 3. Synthesize XII-a with XI_a. Printed by the cooperative (please read the notes on the back before filling out this page) according to the method of step 3 in Example 1, derived from cyclopropylacetylene (30% by weight toluene / THF / hexane, 24.9ml, 0.113 mole) The solution of XI_a (6.28 g, 25.1 mmol) was processed by the lithium block, and the obtained crude yellow oily substance was dissolved in acetone and concentrated under reduced pressure to produce a yellow solid substance, which was 5.98 after crystallization from acetone. G (75%) of the desired product · mp 86.5-88.5 ° C; 4 NMR (300 MHz, acetone-d6) d 9.01 (br s, 1H), 7.46 (br s, 1H), 7.44-7.35 (m, 1H), 6.86 · 6 · 81 (m, 1H), 1.41-1.37 (m, 1H), 0.90-0.83 (m, 1H), 0.74-0.69 (m, -39-) This paper size applies Chinese national standards (CNS) A4 specification (21 OX 297 mm) " 一 '587078 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Invention Description (37) 1H); 19F NMR (282 MHz, acetone-d6) d -83.3 (d, J = 12.9, 1), -136.04-136.23 (m, 1), -148.14-148.26 (m, 1); IR (KBr precipitate) 1706, 1516, 1442, 1246, 1214, 1196 cnT1 ; C14H1 () F5N20 Calculated MS (Cl) m / e: 317.071329, found 317.070836; 317 (MH +, 100), 334 (M + NH4 +, 62); calculated and analyzed C14H9F5N20: C, 53.17; H, 2.88; N, 8.87; Discovery · C, 53.30; H, 3.16; N, 8.53 〇 Example 1 1 Preparation of (+ /-) -5,6 · difluoro-4 · isopropylethynyl-4-trifluoromethyl-3,4 -Dihydro (1 hydrogen) -quinazolinone (R4 = isopropyl) According to the method of step 3 of Example 1 to derive from 3-methyl-1 -butyl block (8.87 g, 13.3 ml, 0.130 mol) After treatment of XI-a (7.24 g of '2 8 · 9 Emole) solution' with lithium acetylide, the obtained crude material was purified by flash chromatography (2.5% MeOH / CH2Cl2) to obtain a yellow oily substance. 6.77 g (74%) of the desired product can be produced after crystallization from acetone: mp 79-80 Ό; 4 NMR (300 MHz acetone-d6) d 9.02 (br s, 1H), 7.50 (br s, 1H), 7.44- 7.35 (m, 1H), 6.87-6.82 (m, 1H), 2.69-2.65 (m, 1H), 1.17 (dd, J = 7.0 Hz, 6H); 19F NMR (282 MHz, acetone-d6) d-83.4 (d, J = 12.9, l), 135.79-135.94 (m, l), -148.14- 148.26 (m, 1); C14H12F5N20 Calculated MS (Cl) m / e · 319.086979, found 319 .087376; 319 (MH +, 100), 336 (M + NH4 +, 76) 〇 Example 12 Preparation of (+ /)-5,6-difluoro · 4- (2-pyridyl) ethynyl_4-tri Fluoromethyl--40- This paper size is applicable to Chinese National Standard (CNS) A4 (210X 297mm) (Please read the precautions on the back before 4-writing this page)
、1T 經濟部中央標準局員工消費合作社印製 587078 A7 ___ B7 五、發明説明(38 ) 3,4-二氫(1氫)-^1奎峻琳酮(尺4 = 2_?比淀基) 根據範例1步驟3的方法,以衍生自2 -乙炔吡啶(0.19克, 1.80毫莫耳)之炔化鋰處理XI-a (100毫克,0.400毫莫耳) 溶液,利用閃火層析法(4% MeOH/CH2Cl2)純化所得粗製物 質後,可產生83毫克(59%)所要的產物:mp 219-220 °C ; NMR (300 MHz,丙酮-d6))d 9.15 (br s,1H),8.61 (d, J=4.4 Hz,1H),7.88-7.82(m,2H),7.63 (dd, J=7.0,1.1Hz, 1H) 7.47-7.42 (m, 2H), 6.94-6.88 (m, 1H), 19F NMR (282 MHz,丙酮-d6)d-82.8 (d,J=12.9, 3),-135.78-135.93 (m,1), •147.86-147.98 (m,1) ; IR (KBr 沉澱物)1 712, 1470,1450, 1430,1416,1264,1238,1226,1198,1186 cm·1 ; C16H9F5N30 計算所得 MS (Cl) m/e : 354.066578 ,發現 354.067821 ; 354 (MH+, 100)。 範例13 製備( + /-)-5,6-二氟-4 -乙基乙块基-4-三氟甲基-3,4-二 氫(1氫)峻淋酮(R4 = 2-乙基) 根據範例1步驟3的方法,以衍生自1 - 丁炔(9 7毫克, 1.80毫莫耳)之炔化鋰處理XI_a (100毫克,0.400毫莫耳) 溶液,利用HPLC (2.5% MeOH/CH2Cl2)純化所得之粗製物 質後,可得69毫克(57%)所要的產物:mp 191-194X: ; ijj NMR (300 MHz,丙酮-d6)ci 9.03 (br s,1H),7·50 (br s,1H), 7.45-7.35 (m,1H), 6.87-6.82 (m,1H),2.34-2.27 (m,2H), 1.20-1.15 (m,3H) ; 19F NMR (282 MHz,丙酮-d6)d -83.3 (d, J=12.9, 3),-135·79-135·98 (m,1),-148.16-148.29(m, 1); -41 - 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) ^ (請先閱讀背面之注意事項再资寫本頁)1.1T printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs. A solution of XI-a (100 mg, 0.400 mmol) was treated with lithium acetylide derived from 2-acetylenepyridine (0.19 g, 1.80 mmol) according to the method of Step 3 of Example 1, and flash chromatography ( 4% MeOH / CH2Cl2) after purification of the crude material, 83 mg (59%) of the desired product was produced: mp 219-220 ° C; NMR (300 MHz, acetone-d6)) d 9.15 (br s, 1H), 8.61 (d, J = 4.4 Hz, 1H), 7.88-7.82 (m, 2H), 7.63 (dd, J = 7.0, 1.1Hz, 1H) 7.47-7.42 (m, 2H), 6.94-6.88 (m, 1H ), 19F NMR (282 MHz, acetone-d6) d-82.8 (d, J = 12.9, 3), -135.78-135.93 (m, 1), • 147.86-147.98 (m, 1); IR (KBr precipitate ) 1 712, 1470, 1450, 1430, 1416, 1264, 1238, 1226, 1198, 1186 cm · 1; C16H9F5N30 calculated MS (Cl) m / e: 354.066578, found 354.067821; 354 (MH +, 100). Example 13 Preparation of (+ /-)-5,6-difluoro-4 -ethylethyl block-4-trifluoromethyl-3,4-dihydro (1 hydrogen) benone (R4 = 2-ethyl Based on the method of Step 3 of Example 1, a solution of XI_a (100 mg, 0.400 mmol) was treated with lithium alkynide derived from 1-butyne (97 mg, 1.80 mmol) using HPLC (2.5% MeOH / CH2Cl2) After purification of the obtained crude material, 69 mg (57%) of the desired product was obtained: mp 191-194X:; ijj NMR (300 MHz, acetone-d6) ci 9.03 (br s, 1H), 7.50 (br s, 1H), 7.45-7.35 (m, 1H), 6.87-6.82 (m, 1H), 2.34-2.27 (m, 2H), 1.20-1.15 (m, 3H); 19F NMR (282 MHz, acetone -d6) d -83.3 (d, J = 12.9, 3), -135 · 79-135 · 98 (m, 1), -148.16-148.29 (m, 1); -41-This paper size applies to Chinese national standards (CNS) A4 size (210X297 mm) ^ (Please read the precautions on the back before writing this page)
、1T .__ 587078 Μ ____ Β7 _ 五、發明説明(39 ) IR (KBr 沉澱物)1704,1686,1518, 1444, 1244, 1210, 1192, 1172 cm1 ; C13H10F5N2O 計算所得之 MS (Cl) m/e : 305.071329 ,發現 305.071146 ; 305 (MH+,100); C13H9F5N20 計算分析:C,51.33 ; Η,2·98 ; Ν,9·22 ;發 現:C, 51.00 ; Η, 2.79 ; Ν, 8.99 。 範例14 製備( + /_)·5,6_二氟_4-苯基乙块基-4-三氟甲基_3,4·二 氫(1氫)-4峰琳酮(R4 =苯基) 根據範例1步驟3的方法,以衍生自苯基乙块(〇·ΐ8克, 0.20毫升,1.80毫莫耳)之块化鋰處理XI-a (1〇〇毫克, 0.400 毫莫耳)溶液,利用 HPLC (2.5% MeOH/CH2Cl2)純化 所得之粗製物質後,可得92毫克(6 5%)所要的產物:ifj NMR (300 mhz,丙酮9.14 (br s,1H),7.80 (br s,1H), 7.57-7.54 (m,2H),7.49-7.40 (m,4H),6.92-6.87 (m,1H); 19F NMR (282 MHz,丙酮-(16)6-83.0((1,>12.9,3),-136.08-136.27(m,1),·147·87·148.00(ιη, 1) ; ; C17H10F5N2O 計算所 得之 MS (Cl) m/e : 353.071329,發現 353.071716 ; 353 (MH+,42),370 (M+NH4+,100) 〇 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再療寫本頁} 、-口 範例15 製備(+ /-)-5,6_二氟-4-異戊基-4-三氟甲基_3,4-二氫(1 氫)喹唑啉酮(R4=異丙基) 自 ΧΙΙ-a 合成 ΧΠΙ-a 在H2(l大氣壓)下,用10%碳(35毫克)上pd處理内含 XIII-a(R4=異丙基)(26毫克,82毫莫耳)之乙醇〇毫升) -42-、 1T .__ 587078 Μ ____ Β7 _ 5. Description of the invention (39) IR (KBr precipitate) 1704, 1686, 1518, 1444, 1244, 1210, 1192, 1172 cm1; C13H10F5N2O Calculated MS (Cl) m / e : 305.071329, found 305.071146; 305 (MH +, 100); C13H9F5N20 calculation analysis: C, 51.33; Η, 2.98; Ν, 9.22; found: C, 51.00; Η, 2.79; Ν, 8.99. Example 14 Preparation of (+ / _) · 5,6_difluoro_4-phenylethyl 4-trifluoromethyl_3,4 · dihydro (1hydro) -4peaklinone (R4 = benzene Based on the method of Step 3 of Example 1, XI-a (100 mg, 0.400 mmol) was treated with lithium block derived from phenylethyl block (0.88 g, 0.20 ml, 1.80 mmol). The solution was purified by HPLC (2.5% MeOH / CH2Cl2) to obtain 92 mg (6 5%) of the desired product: ifj NMR (300 mhz, acetone 9.14 (br s, 1H), 7.80 (br s , 1H), 7.57-7.54 (m, 2H), 7.49-7.40 (m, 4H), 6.92-6.87 (m, 1H); 19F NMR (282 MHz, acetone- (16) 6-83.0 ((1, > 12.9,3), -136.08-136.27 (m, 1), · 147 · 87 · 148.00 (ιη, 1);; MS (Cl) m / e calculated by C17H10F5N2O: 353.071329, found 353.071716; 353 (MH +, 42), 370 (M + NH4 +, 100) 〇 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before writing this page) 、-口 Example 15 Preparation (+ /-)-5, 6_Difluoro-4-isopentyl-4-trifluoromethyl_3,4-dihydro (1 hydrogen) quinazolinone (R4 = isopropyl) Synthesized from XΙΙ-a a Treatment with ethanol containing XIII-a (R4 = isopropyl) (26 mg, 82 mmol) in H2 (l atm) with pd on 10% carbon (35 mg) -42-
經濟部中央標準局員工消費合作社印製 587078 A7 B7 五、發明説明(4〇 ) 及EtO Ac (0.5毫升)溶液16小時,用眞空過濾法經硅藻土 Celite過濾去除催化劑,而以EtAOc清洗過濾後所得之固 態物,在減壓下濃縮濾液後,可得26毫克(100%)所要的 產物’無須進一步的純化:1H NMR (300 MHz,丙嗣-d6) ci 8.88 (br s,1Η),7.41-7.31 (m,1Η), 6.89-6.81 (m,2Η), 2·55_2.50 (m, 1H), 1.64-1.45 (m,2H),1·06_1·02 (m,1H), 0.89 (dd, J=6.6, 2.2Hz, 6H) ; 19F NMR (282 MHz 丙酮-d6) d-83.22 (d,J=12.1,3),-138.97-139.13(m,l),-148.46-148.58 (m,1) ; IR (KBr 沉澱物)1700,1678,1518,1438, 1252, 1 188, 1 172 cnT1 ; C14H16F5N20 計算所得之 MS (Cl) m/e : 323.118280,發現:323.116703 ; 323 (MH+,100), 340 (M+NH/,57) 〇 範例16 製備( + /-)-4 -丁基-5,6 -二氟-4-三氟曱基- 3,4 -二氫(1 氯)·峻峻T?林嗣(R4 =乙基) 根據範例15的步驟,在H2下,用10%碳上Pd處理内含 XIII-a (R4=乙基)(20毫克,66毫莫耳)之乙醇(1毫升)及 EtOAc (0.5 毫升)溶液,以 HPLC (2.5% MeOH/CH2Cl2)純化 後,可得12毫克(56%)所要的產物:4 NMR (300 MHz, 丙酮-d6)d 8.89 (br s,1H), 7.41-7.32 (m,1H),6·86·6·81 (m, 2Η),2.57-2.47 (m,1Η),1.56-1·15 (m, 5Η),〇·88 (t,J=7.3 Hz,3H) ; 19F NMR (282 MHz,丙酮-d6) -83.19-83.24 (m, 1),139.14 (s,1),-148.49-148.62 (m,1) ; C13H14F5N20 計算 所得之 MS (Cl) m/e : 309.102629,發現:309.103555 ; -43- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X 297公釐) (請先閲讀背面之注意事項再填寫本頁) 訂 587078Printed by the Consumers' Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs 587078 A7 B7 V. Description of the invention (40) and EtO Ac (0.5 ml) solution for 16 hours, the catalyst was removed by diatomite Celite filtration using air filtration, and EtAOc was used to clean the filter After the solid obtained after concentration of the filtrate under reduced pressure, 26 mg (100%) of the desired product was obtained without further purification: 1H NMR (300 MHz, propane-d6) ci 8.88 (br s, 1Η) , 7.41-7.31 (m, 1Η), 6.89-6.81 (m, 2Η), 2.55_2.50 (m, 1H), 1.64-1.45 (m, 2H), 1.06_1 · 02 (m, 1H), 0.89 (dd, J = 6.6, 2.2Hz, 6H); 19F NMR (282 MHz acetone-d6) d-83.22 (d, J = 12.1, 3), -138.97-139.13 (m, l), -148.46-148.58 (m, 1); IR (KBr precipitate) 1700, 1678, 1518, 1438, 1252, 1 188, 1 172 cnT1; C14H16F5N20 MS (Cl) m / e: 323.118280, found: 323.116703; 323 (MH + , 100), 340 (M + NH /, 57) 〇 Example 16 Preparation of (+ /-) 4-butyl-5,6-difluoro-4-trifluorofluorenyl-3,4-dihydro (1 Chlorine) · Junjun T? Lin Ying (R4 = ethyl) According to the procedure of Example 15, under H2, treat with 10% carbon on Pd A solution containing XIII-a (R4 = ethyl) (20 mg, 66 mmol) in ethanol (1 ml) and EtOAc (0.5 ml) was purified by HPLC (2.5% MeOH / CH2Cl2) to obtain 12 mg ( 56%) desired product: 4 NMR (300 MHz, acetone-d6) d 8.89 (br s, 1H), 7.41-7.32 (m, 1H), 6.86 · 6 · 81 (m, 2Η), 2.57- 2.47 (m, 1Η), 1.56-1 · 15 (m, 5Η), 0.88 (t, J = 7.3 Hz, 3H); 19F NMR (282 MHz, acetone-d6) -83.19-83.24 (m, 1 ), 139.14 (s, 1), -148.49-148.62 (m, 1); MS (Cl) m / e calculated by C13H14F5N20: 309.102629, found: 309.103555; -43- This paper standard applies to Chinese National Standard (CNS) A4 size (210X 297mm) (Please read the precautions on the back before filling this page) Order 587078
XIV- A7 B7 五、發明説明(41 ) 309 (MH+,100),326 (M+NH/,62) 〇 範例1 7 、 製備(+ /-)_4_環丙基乙块基-6-氟-4-三氟甲基-3,4-二氫 -2(1氫峻琳酮(R4 =環丙基) (請先閲讀背面之注意事項再填寫本頁)XIV- A7 B7 V. Description of the invention (41) 309 (MH +, 100), 326 (M + NH /, 62) 〇 Example 17 7. Preparation of (+/-) _ 4-cyclopropylethyl-6-fluoro -4-Trifluoromethyl-3,4-dihydro-2 (1-Hydroxylinone (R4 = cyclopropyl) (Please read the precautions on the back before filling this page)
TMF/CHtCCR^ n-BuLi/0 °C 1 0 7; Pd/C Μ 2 ( 1 a tin) EtOH/EtOAc: PV:TMF / CHtCCR ^ n-BuLi / 0 ° C 1 0 7; Pd / C Μ 2 (1 a tin) EtOH / EtOAc: PV:
NU rr、0 XVIII-aNU rr, 0 XVIII-a
XV- XV11 R^1XV- XV11 R ^ 1
XIX- 經濟部中央標準局員工消費合作社印製 XVI -rXIX- Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economy XVI -r
步驟1、自XIV_a合成XV 用範例1步驟1所述之方法,以二甲基胺基吡啶及異氰 酸單矽烷基酯處理XIII-a (3.Q7克,14.8毫莫耳)之溶液 後,可得2.81克(76%)所要之產物。 步驟2、自XV-a合成XVI-a -44- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X 297公釐) 經濟部中央標準局員工消費合作社印製 587078 A7 B7 五、發明説明(42 ) 用範例1步驟2所述之方法,將xv-a (6.74克,25.1毫 莫耳)溶液在甲苯中加熱回流後,可得〇·73克(94%)所要之 產物。 步驟3、自XVI-a合成XVII-a 根據範例1步驟3的方法,以衍生自環丙基乙块(1.43毫 升之30%甲苯/THF/己烷,1.94毫莫耳)之炔化鋰處理 XVI_a (100毫克,0.431毫莫耳)溶液,利用HPLC (2.5% MeOH/CH2Cl2)純化所得之粗製物質後,可得44毫克(34%) 所要的產物:mp 155 °C ; 4 NMR (300 MHz 丙酮-d6) d 8.86(brs,lH),7.36(brs,lH),7.30-7.27 (m,lH),7.22-7.15 (m, 1H), 7.04-6.99 (m, 1H), 1.47-1.42 (m, 1H), 0.90-0.87 (m,2H),0·76·0·75 (m,2H) ; 19F NMR (282 MHz,丙酮 •d6)d-82.86, -123.36-123.44 ; C14HnF4N20 計算所得之 MS (Cl) m/e : 299.080751 ,發現 299.079976 ; 299 (MH+, 100) 〇 範例1 8 製備( + /-)-6 -氟-4-異丙基乙炔基-4-三氟甲基·3,4_二氫 _2(1氫奎峻琳酮(R4 =異丙基) 根據範例1步驟3的方法,以衍生自3 -甲基-1 - 丁炔 (〇·13克,0.20毫升,1.94毫莫耳)之炔化鋰處理XVI-a (100毫克,0.431毫莫耳)溶液,利用HPLC (2.5% MeOH/CH2Cl2)純化所得之粗製物質後,可得24毫克(18%) 所要的產物:mpl58°C; WNMRpOO MHz,丙酮_d6)d 9.07 (br s, 1H), 7.60 (br s, 1H)? 7.32-7.30 (m, 1H), 7.24- -45- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) (請先閲讀背面之注意事項再療寫本頁)Step 1. Synthesis of XV from XIV_a After treating the solution of XIII-a (3.Q7 g, 14.8 mmol) with dimethylaminopyridine and monosilyl isocyanate by the method described in Example 1, Step 1 , Can obtain 2.81 g (76%) of the desired product. Step 2. Synthesize XVI-a -44 from XV-a. This paper size is applicable to Chinese National Standard (CNS) A4 (210X 297 mm). Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs. 587078 A7 B7 5. Description of the invention ( 42) Using the method described in step 2 of Example 1, the xv-a (6.74 g, 25.1 mmol) solution was heated under reflux in toluene to obtain 0.73 g (94%) of the desired product. Step 3. Synthesis of XVII-a from XVI-a According to the method in step 3 of Example 1, the lithium acetylide derived from cyclopropyl ethyl block (1.43 ml of 30% toluene / THF / hexane, 1.94 mmol) was treated. XVI_a (100 mg, 0.431 mmol) was purified by HPLC (2.5% MeOH / CH2Cl2) to obtain 44 mg (34%) of the desired product: mp 155 ° C; 4 NMR (300 MHz Acetone-d6) d 8.86 (brs, lH), 7.36 (brs, lH), 7.30-7.27 (m, lH), 7.22-7.15 (m, 1H), 7.04-6.99 (m, 1H), 1.47-1.42 ( m, 1H), 0.90-0.87 (m, 2H), 0.776 · 0.75 (m, 2H); 19F NMR (282 MHz, acetone • d6) d-82.86, -123.36-123.44; C14HnF4N20 Calculated MS (Cl) m / e: 299.080751, found 299.079976; 299 (MH +, 100). Example 1 8 Preparation of (+/-)-6-fluoro-4-isopropylethynyl-4-trifluoromethyl · 3 , 4-dihydro_2 (1 hydroquinone (R4 = isopropyl)) According to the method of step 3 of Example 1 to derive from 3-methyl-1 -butyne (0.13 g, 0.20 ml, 1.94 millimolars) of a solution of XVI-a (100 mg, 0.431 millimolars) treated with lithium acetylide and purified by HPLC (2.5% MeOH / CH2Cl2) After preparing the substance, 24 mg (18%) of the desired product can be obtained: mpl58 ° C; WNMRpOO MHz, acetone_d6) d 9.07 (br s, 1H), 7.60 (br s, 1H)? 7.32-7.30 (m, 1H), 7.24- -45- This paper size is applicable to China National Standard (CNS) A4 (210X297mm) (Please read the precautions on the back before writing this page)
、1T 587078 A7 五、發明説明(43 ) 7.16 (m,1H),7.05-6.99 (m,1H),2.77-2.67 (m,1H),1·20 (dd,J=7.0, 2.6 Hz,6H) ; 19F NMR (282 MHz,丙酮-d6)d -82.95, -123.41-123.49 ; Ci4H13F4N20 計算所得之 MS (Cl) m/e : 301.096401,發現 301.096235 ; 301 (MH+,100)。 範例19 製備( + /-)_6 -氟_4_(2-吡啶基)乙炔基·4-三氟曱基-3,4_ 二氫·2(1氫)-喹唑啉酮(R4 = 2-吡啶基) 根據範例1步驟3的方法,以衍生自2 -乙炔吡啶(0.20 克,1.94毫莫耳)之块化鋰處理XVI-a (100毫克,0.431毫 莫耳)溶液,利用HPLC (2.5% MeOH/CH2Cl2)純化所得粗 製物質後,可產生65毫克(45%)所要的產物:mp 155 °C ; 4 NMR (300 MHz,丙酮-d6)) β 9.02 (br s,1H),8.60 (d, J=4.0Hz, 1H),7.87-7.78 (m, 2H),7.66 (d,J=7.7 Hz,1H), 7·45·7·41 (m,2H),7.26-7.20 (m,1H),7.09-7.05 (m,1H); 19F NMR (282 MHz,丙酮-d6) d -82.36, -122.94-123.02 ; C16H1()F4N30 計算所得 MS (Cl) m/e : 336.076000,發現 336.074156 ; 336 (MH+, 25)。 範例2 0 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意_事項再療寫本頁) 製備( + Λ)_6_氟-4 -乙基乙块基-4-三氟甲基-3,4_二氫_ 2(1氫)·ρ奎峻琳酉同(r4 =乙基) 根據範例1步驟3的方法,以衍生自1-丁炔(0.10克, 1.94毫莫耳)之炔化鋰處理XVI_a (100毫克,0.431毫莫耳) 溶液,利用HPLC (2.5% MeOH/CH2Cl2)純化所得粗製物質 後,可產生40毫克(33%)所要的產物:mp 190 X: ; 4 -46 - 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) " 經濟部中央標準局員工消費合作社印製 587078 A7 B7 五、發明説明(44 ) NMR (300 MHz,丙酮-d6))d 8.86 (br s,1H),7.38 (br s,1H), 7.34-7.31 (m,1H), 7.22-7.16 (m,1H),7.05-7.00 (m,1H), 2.04-2.01 (m, 2H), 1.19-1.14 (m, 3H) ; 19F NMR (282 MHz, 丙酮-d6)d-75.392, -123.42-123.50 ; C13HuF4N20 計算所得 MS (Cl) m/e : 287.080751,發現 287.080740 ; 287 (MH+, 100) 〇 範例2 1 製備( + /_)_6 -氟-4-苯基乙炔基-4_三氟甲基-3,4-二氫-2(1氫)·嗜峻琳酮(R4 =苯基) 根據範例1步驟3的方法,以衍生自苯基乙炔(0·20克, 0.21毫升,1.94毫莫耳)之块化鋰處理XVI-a (100毫克, 0.431 毫莫耳)溶液,利用 HPLC (2.5% MeOH/CH2Cl2)純化 所得粗製物質後,可產生41毫克(28%)所要的產物:mp 107 °C ; 4 NMR (300 MHz,丙酮-d6) d 9.00 (br s,1H), 7.69 (br s,1H),7.63-7.59 (m,2H),7.50-7.40 (m,4H), 7.27-7.20 (m, 1H), 7.10-7.05 (m, 1H) ; 19F NMR (282 MHz, 丙酮-d6)d-82.56, -122.99-123.07 ; CnHuFdlSbO 計算所得 MS (Cl) m/e : 335.080751,發現 335.082057 ; 335(MH+, 74),352(MH+,100)。 範例2 2 製備( + /-)·6·氟·4 -異戊基·4·三氟甲基-3,4·二氫-2(1 氫)-4唑琳酮(R 4 =異丙基) 自 XVII-a 合成 XVIII-a 根據範例1 5的步驟,在Η 2下,用1 〇%碳上P d處理内含 -47- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) (請先閱讀背面之注意事項再4-寫本頁)1T 587078 A7 V. Description of the invention (43) 7.16 (m, 1H), 7.05-6.99 (m, 1H), 2.77-2.67 (m, 1H), 1.20 (dd, J = 7.0, 2.6 Hz, 6H ); 19F NMR (282 MHz, acetone-d6) d -82.95, -123.41-123.49; Ci4H13F4N20 calculated MS (Cl) m / e: 301.096401, found 301.096235; 301 (MH +, 100). Example 19 Preparation of (+ /-) _ 6 -fluoro_4_ (2-pyridyl) ethynyl · 4-trifluorofluorenyl-3,4_dihydro · 2 (1hydro) -quinazolinone (R4 = 2- Pyridyl) A solution of XVI-a (100 mg, 0.431 mmol) was treated with lithium agglomerate derived from 2-acetylenepyridine (0.20 g, 1.94 mmol) according to the method of Step 3 of Example 1, using HPLC (2.5 % MeOH / CH2Cl2) After purification of the obtained crude material, 65 mg (45%) of the desired product was produced: mp 155 ° C; 4 NMR (300 MHz, acetone-d6)) β 9.02 (br s, 1H), 8.60 ( d, J = 4.0Hz, 1H), 7.87-7.78 (m, 2H), 7.66 (d, J = 7.7 Hz, 1H), 7.45 · 7 · 41 (m, 2H), 7.26-7.20 (m, 1H), 7.09-7.05 (m, 1H); 19F NMR (282 MHz, acetone-d6) d -82.36, -122.94-123.02; C16H1 () F4N30 MS (Cl) m / e: 336.076000, found 336.074156; 336 (MH +, 25). Example 2 0 Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs (please read the precautions on the back first and then write this page) Preparation (+ Λ) _6_fluoro-4 -ethylethyl block-4-trifluoromethyl -3,4_dihydro_ 2 (1 hydrogen) · ρ Kui Junlin (r4 = ethyl) According to the method of step 3 of Example 1, derived from 1-butyne (0.10 g, 1.94 mmol) ) Treatment of XVI_a (100 mg, 0.431 mmol) with lithium acetylide, and purification of the crude material by HPLC (2.5% MeOH / CH2Cl2), can produce 40 mg (33%) of the desired product: mp 190 X :; 4 -46-This paper size applies Chinese National Standard (CNS) A4 (210X297 mm) " Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 587078 A7 B7 V. Description of the invention (44) NMR (300 MHz, acetone- d6)) d 8.86 (br s, 1H), 7.38 (br s, 1H), 7.34-7.31 (m, 1H), 7.22-7.16 (m, 1H), 7.05-7.00 (m, 1H), 2.04-2.01 (m, 2H), 1.19-1.14 (m, 3H); 19F NMR (282 MHz, acetone-d6) d-75.392, -123.42-123.50; C13HuF4N20 MS (Cl) m / e: 287.080751, found 287.080740; 287 (MH +, 100) 〇 Example 2 1 system (+ / _) _ 6 -Fluoro-4-phenylethynyl-4_trifluoromethyl-3,4-dihydro-2 (1hydro) · Nastilone (R4 = phenyl) Follow the procedure in Example 1 3 method, treating a solution of XVI-a (100 mg, 0.431 mmol) with lithium lumines derived from phenylacetylene (0.20 g, 0.21 ml, 1.94 mmol) using HPLC (2.5% MeOH / CH2Cl2) after purification of the crude material, 41 mg (28%) of the desired product was produced: mp 107 ° C; 4 NMR (300 MHz, acetone-d6) d 9.00 (br s, 1H), 7.69 (br s, 1H ), 7.63-7.59 (m, 2H), 7.50-7.40 (m, 4H), 7.27-7.20 (m, 1H), 7.10-7.05 (m, 1H); 19F NMR (282 MHz, acetone-d6) d- 82.56, -122.99-123.07; MS (Cl) m / e calculated by CnHuFdlSbO: 335.080751, found 335.082057; 335 (MH +, 74), 352 (MH +, 100). Example 2 2 Preparation of (+ /-) · 6 · fluoro · 4-isopentyl · 4 · trifluoromethyl-3,4 · dihydro-2 (1 hydrogen) -4 zolinone (R 4 = isopropyl Base) Synthesis of XVIII-a from XVII-a According to the procedure of Example 15, under Η 2 with P d at 10% carbon, the content is included. -47- This paper size applies Chinese National Standard (CNS) A4 specification (210X297 (Mm) (Please read the notes on the back before 4-writing this page)
、1T 587078 A7 B7 五、發明説明(45 ) XVII-a (R4=異丙基)(26毫克,87毫莫耳)之乙醇(1毫升) 及EtOAc (〇· 5毫升)溶液,可得1 5毫克(58%)所要的產 物’無須進一步的純化:mp 179 C ; H NMR (300 MHz, 丙酮-d6)d 7.02-6.97 (m,2H),6.80-6.76 (m,1H),2.18-2.09 (m,2H),1.92-1.82 (m,2H), 1.52-1.45 (m,1H),0.88-0.79 (m,6H) ; 19F NMR (282 MHz,丙酮-d6)d 82.60, -123.72, -123.84 ; C14H17F4N20 計算所得之 MS (Cl) m/e : 305.127707,發現:305.126790 ; 305 (MH+,100)。 範例2 製備(+ /-)-6-氟_4-(2,-2-吡啶基)乙块基_4_三氟甲基-3,4-二氫·2(1氫)-喹唑啉酮(R4 = 2-吡啶基) 經濟部中央標準局員工消費合作社印製 (請先閲讀背面之注意事項再餐寫本頁) . 根據範例1 5的步驟,在Η 2下,用1 〇%碳上P d處理内含 XVII-a (R4 = 2-吡啶基)(33毫克,99毫莫耳)之乙醇(1毫 升)及EtOAc (0.5毫升)溶液,可得1〇愛克(30%)所要的產 物,無須進一步的純化:mp 88 °C ;NMR (300 MHz丙 酮-d6)d 8.35 (d,J=4.4 Hz,1H),7.63 (dt,J=7.7,1.5 Hz, 1H), 7.20-7.13 (m, 3H), 7.04-6.98 (m, 1H), 6.83-6.79 (m, 1H),2.84-2.78 (m,1H),2.68-2.48 (m, 2H),2.27-2.06 (m, 1H) ; 19F NMR (282 MHz,丙酮46)6-82.58, -1 23.26, -123.34 ; C16H14F4N30 計算所得之 MS (Cl) m/e : 340.107300,發現:340.107719 ; 340 (MH+,100)。 範例24_ 製備( + /- )- 4- 丁基-6-氣-4-二氣甲基_3,4· 一 氮 _2(1 氫)-τί奎峻淋_( R4 =乙基) -48- 本紙張尺度適用中國國家標準^灿丨以規格“丨⑼別公釐) 經濟部中央標準局員工消費合作社印製 587078 A7 B7 五、發明説明(46 ) 根據範例1 5的步驟’在Η2下’用1 〇%碳上P d處理内含 XVII-a (R4=:乙基)(24毫克,8 4毫莫耳)之乙醇(1毫升) 及EtOAc (〇·5毫升)溶液,可得24毫克(100%)所要的產 物,無須進一步的純化:mP I98 °C ; 4 NMR (300 MHz, 丙酮-(16)4 7.03-6.97 (m,2H),6·80·6·76 (m,1H),2.18-2.11 (m,1H),1.90-1.81 (m,1H),1.30-1.19 (m,3H),0.97-0.80 (m,4H) ; 19F NMR (282 MHz,丙酮-d6) β -82.692, -123.78 -123.86 ; C13H15F4N20 計算所得之 MS (Cl) m/e : 291.112051,發現:291.1 12227 ; 291 (MH+,100)。 範例2 5 製備( + /· )-6-氟-4_苯基乙基-4-三氟甲基-3,4-二氳-2(1 氫)· p奎峻琳銅(R 4 =苯基) 根據範例15的步驟,在112下,用10%碳上Pd處理内含 XVII_a (R4=苯基)(30毫克,90毫莫耳)之乙醇(1毫升) 及EtOAc (0.5毫升)溶液,可得20毫克(67%)所要的產 物,無須進一步的純化:tnp 98 °C ; 4 NMR (300 MHz,丙 酮-d6)ci 7.18-6.99 (m,7H),6.84-6.79 (m,1H),2.68-2.60 (m,1H),2.48-2.12 (m,3H) ; 19F NMR (282 MHz,丙酮-d6) d-82.67, -123.24-123.32 ; C17H15F4N20 計算所得之 MS (Cl) m/e : 339.1 12051,發現:339.110781 ; 339 (MH+,100)。 範例2 6 製備( + /-)·6-氟-4 -甲基丙炔基-4-三氟甲基-3,4-二氫-2(1氮)-ρ奎峰ρ林嗣(R4=甲基) 自 XVI-a 合成 XIX-a -49- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) (請先閲讀背面之注意事項再番寫本頁) 、1Τ 587078 Μ Β7 經濟部中央標準局員工消費合作社印製 五、發明説明(48 ) R! 化合物 r! r! 化舍验 6-C1 IV-a 6-Cl IV-b 6-Cl IV-c 6-MeO vm-a 6-MeO vm-b 6-MeO vm-c 5,6-diF ΧΠ-a 5,6-diF ΧΠ-b 5,6-diF xn-c 6-F ΧΥΠ-a 6-F xvn^b 6-F xvn-c 範例2 7及j 8 製備(-)-6_氯_4_環丙基乙块基-4-三氟甲基·3,4_二氫-2 (1氫)-峻峻淋酮(範例2 7 ) 及(+ )- 6·氣-4-環丙基乙決基-4-三氟甲基_3,4-二氫- 2 (1氫)·喹唑啉酮(範例2 8 ) 自IV-a(R4 =環丙基)分離IV-b,c 利用 Chiral cel OD 管柱 ’ 3 % 異丙醇,5% CH2C12 及 92% 己烷之對掌HPLC於常溫下,以1.0毫升/分鐘的流速及 250微毫米的偵測波長,可分離鏡像異構物分別高過99% 與99.4%之1\^-1)及1\^-(:,1\^1):111卩 106-109。(3; [a]D25-60.34〇(c=0.274, MeOH)。IV-c : mp 105-107 °C ; [a]D25+58.330 (c=0.288, MeOH)。 範例2 9及3 0 製備(+ )_4_環丙基乙炔基-5,6-二氟三氟甲基_3,4_二 氫-2 (1氫)-喹唑啉酮(範例2 9 )及(-)-4 ·環丙基乙炔基-5,6-二氟-4-三氟甲基-3,4-二氫-2(1氫)-喹唑啉酮(,範例 3 0 ) 自XII-a(R4 =環丙基)分離XII-b,c 利用Chiralpak AD管柱,5%水及95%甲醇HPLC於常溫 -51 - 本紙張尺度適用中國國家標準(CNS)A4規格(210X297公釐) (請先閱讀背面之注意事項存填寫本頁), 1T 587078 A7 B7 V. Description of the invention (45) XVII-a (R4 = isopropyl) (26 mg, 87 mmol) in ethanol (1 ml) and EtOAc (0.5 ml) solution, can get 1 5 mg (58%) of the desired product 'without further purification: mp 179 C; H NMR (300 MHz, acetone-d6) d 7.02-6.97 (m, 2H), 6.80-6.76 (m, 1H), 2.18- 2.09 (m, 2H), 1.92-1.82 (m, 2H), 1.52-1.45 (m, 1H), 0.88-0.79 (m, 6H); 19F NMR (282 MHz, acetone-d6) d 82.60, -123.72, -123.84; C14H17F4N20 MS (Cl) m / e: 305.127707, found: 305.126790; 305 (MH +, 100). Example 2 Preparation of (+/-)-6-fluoro_4- (2, -2-pyridyl) ethyl block_4_trifluoromethyl-3,4-dihydro · 2 (1hydro) -quinazole Porphyrinone (R4 = 2-pyridyl) Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before dining and writing this page). Follow the steps in Example 15 under Η 2 and use 1 〇 A solution of XVII-a (R4 = 2-pyridyl) (33 mg, 99 mmol) in ethanol (1 ml) and EtOAc (0.5 ml) was treated with P d on% carbon to obtain 10 gram (30 %) Desired product without further purification: mp 88 ° C; NMR (300 MHz acetone-d6) d 8.35 (d, J = 4.4 Hz, 1H), 7.63 (dt, J = 7.7, 1.5 Hz, 1H) , 7.20-7.13 (m, 3H), 7.04-6.98 (m, 1H), 6.83-6.79 (m, 1H), 2.84-2.78 (m, 1H), 2.68-2.48 (m, 2H), 2.27-2.06 ( m, 1H); 19F NMR (282 MHz, acetone 46) 6-82.58, -1 23.26, -123.34; C16H14F4N30 MS (Cl) m / e: 340.107300, found: 340.107719; 340 (MH +, 100). Example 24_ Preparation of (+ /-)-4-butyl-6-gas-4-digas methyl_3,4 · mononitro_2 (1 hydrogen) -τί Kui Junlin_ (R4 = ethyl)- 48- This paper size applies Chinese national standard ^ Can 丨 with specifications "丨 ⑼mm" Printed by the Staff Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs 587078 A7 B7 V. Description of the invention (46) According to the steps of Example 1 5 'in Η2 Next, a solution of XVII-a (R4 =: ethyl) (24 mg, 84 mmol) in ethanol (1 ml) and EtOAc (0.5 ml) was treated with P d on 10% carbon. 24 mg (100%) of the desired product were obtained without further purification: mP I98 ° C; 4 NMR (300 MHz, acetone- (16) 4 7.03-6.97 (m, 2H), 6.80 · 6 · 76 ( m, 1H), 2.18-2.11 (m, 1H), 1.90-1.81 (m, 1H), 1.30-1.19 (m, 3H), 0.97-0.80 (m, 4H); 19F NMR (282 MHz, acetone-d6) ) β -82.692, -123.78 -123.86; MS (Cl) m / e calculated from C13H15F4N20: 291.112051, found: 291.1 12227; 291 (MH +, 100). Example 2 5 Preparation (+ / ·) -6-fluoro- 4-Phenylethyl-4-trifluoromethyl-3,4-difluorene-2 (1 hydrogen) · p Cujunlin (R 4 = phenyl) according to Example 15 In step 112, a solution of XVII_a (R4 = phenyl) (30 mg, 90 mmol) in ethanol (1 ml) and EtOAc (0.5 ml) containing Pd on 10% carbon was used to obtain 20 mg ( 67%) of the desired product without further purification: tnp 98 ° C; 4 NMR (300 MHz, acetone-d6) ci 7.18-6.99 (m, 7H), 6.84-6.79 (m, 1H), 2.68-2.60 ( m, 1H), 2.48-2.12 (m, 3H); 19F NMR (282 MHz, acetone-d6) d-82.67, -123.24-123.32; C17H15F4N20 MS (Cl) m / e: 339.1 12051, found: 339.110781; 339 (MH +, 100). Example 2 6 Preparation of (+ /-) · 6-fluoro-4 -methylpropynyl-4-trifluoromethyl-3,4-dihydro-2 (1 nitrogen) -ρ 奎 峰 ρ 林 嗣 (R4 = methyl) Synthesized from XVI-a XIX-a -49- This paper size applies to China National Standard (CNS) A4 specification (210X297 mm) (Please read the precautions on the back before (Written on this page), 1T 587078 Μ Β7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (48) R! Compound r! R! Chemical House Test 6-C1 IV-a 6-Cl IV-b 6 -Cl IV-c 6-MeO vm-a 6-MeO vm-b 6-MeO vm-c 5,6-diF ΧΠ-a 5,6-diF ΧΠ-b 5,6-d iF xn-c 6-F χΥΠ-a 6-F xvn ^ b 6-F xvn-c Example 2 7 and j 8 Preparation of (-)-6_chloro_4_cyclopropylethyl-4-trifluoro Methyl · 3,4_dihydro-2 (1H) -junjunone (Example 27) and (+)-6 · Ga-4-cyclopropylethoxy-4-trifluoromethyl_ 3,4-Dihydro-2 (1 hydrogen) · quinazolinone (Example 2 8) Separation of IV-b from IV-a (R4 = cyclopropyl), c using Chiral cel OD column '3% isopropyl Alcohol, 5% CH2C12 and 92% hexane in normal palm HPLC at room temperature, with a flow rate of 1.0 ml / min and a detection wavelength of 250 μm, can separate mirror isomers higher than 99% and 99.4% 1 \ ^-1) and 1 \ ^-(:, 1 \ ^ 1): 111 卩 106-109. (3; [a] D25-60.34〇 (c = 0.274, MeOH). IV-c: mp 105-107 ° C; [a] D25 + 58.330 (c = 0.288, MeOH). Example 2 9 and 30 Preparation (+) _ 4-Cyclopropylethynyl-5,6-difluorotrifluoromethyl_3,4_dihydro-2 (1hydro) -quinazolinone (Example 2 9) and (-)-4 · Cyclopropylethynyl-5,6-difluoro-4-trifluoromethyl-3,4-dihydro-2 (1hydro) -quinazolinone (, Example 30) from XII-a (R4 = Cyclopropyl) Separation XII-b, c using Chiralpak AD column, 5% water and 95% methanol HPLC at room temperature -51-This paper size applies to China National Standard (CNS) A4 (210X297 mm) (Read the notes on the back and fill in this page)
、1T 587078 Μ ______Β7______ 五、發明説明(49 ) 下,以0 · 8毫升/分鐘的流速及2 5 0微毫米的偵測波長,可 分離鏡像異構物分別高過100%與99%之ΧΠ-b及XII-c, XII_b:mpl87〇C;[a]D25 + 1.46o(c=0.274,MeOH)°XII_ c : mp 187.5-188.8 °C ; [a]D25-1.45°(c=0.278, MeOH) 〇 範例3 1及3 2 製備(-)-5,6 -二氟_4·異丙基乙块基·4 -三氟甲基·3,4 -二 氫(1氫)-4峻淋_(範例31)及(+ )_5,6_二氟-4·異丙基乙 炔基-4 -三氟甲基_ 3,4 ·二氫(1氫)-喹唑啉酮(範例3 2 ) 自XII_a (R4=異丙基)分離XII-b,c 利用Chiralpak AD管柱,5%水及95%甲醇HPLC於常溫 下,以0 · 5毫升/分鐘的流速及2 5 0微毫米的偵測波長,可 分離鏡像異構物分別高過100%與99%之ΧΠ-b及XII-c, XII-b : mpl55〇C ; [a]D25-2.14o(c=0.280, MeOH) 〇 ΧΙΙ-c : mp 98 °C ; [a]D25+4.45°(c=0.292, MeOH) 〇 範例3 3及3 4 製備(_)_5,6-二氟-4 -乙基乙炔基-4-三氟甲基-3,4-二氫 (1氳) 口奎峻淋_ (範例3 3 )及(+) 5,6 -二氟-4 -乙基乙块基-4 三氟甲基-3,4 -二氫(1氫)_ p奎峻琳酮(範例3 4 ) 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再參寫本頁) 自 XII-a (R4 =乙基)分離 ΧΠ-b,c 利用AS管柱,2〇%乙醇,及80己垸之對掌HPLC於常 溫下,以1 ·0毫升/分鐘的流速及250微毫米的偵測波長, 可分離鏡像異構物分別高過100%與99.4%之χπ-b及XII-c, XII_b : mp 165-167 〇C 0 XII-c : mp 157-〇C 159。 範例3 5及3 6 -52- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 587078 A7 B7 五、發明説明(50 ) 製備5,6·二氟_4_(2_經基乙基)乙炔基-4_三氟甲基· 3,4·二氫(1氫)-峻峻淋酮(範例35)及5,6 -二、氟- 4- (1•經 基乙基)乙块基-4 -三氟甲基-3,4·二氫(1氫)-峻唑琳酮(範 例3 0) (請先閱讀背面之注意事項再齋寫本頁)、 1T 587078 Μ ______ Β7 ______ 5. In the description of the invention (49), at a flow rate of 0.8 ml / min and a detection wavelength of 250 micrometers, the isomeric isomers can be separated by 100% and 99% respectively. -b and XII-c, XII_b: mpl87 ° C; [a] D25 + 1.46o (c = 0.274, MeOH) ° XII_c: mp 187.5-188.8 ° C; [a] D25-1.45 ° (c = 0.278, MeOH) 〇 Example 3 1 and 3 2 Preparation of (-)-5,6-difluoro-4 · isopropylethyl block · 4-trifluoromethyl · 3,4-dihydro (1 hydrogen) -4jun Leaching_ (Example 31) and (+) _ 5,6_difluoro-4 · isopropylethynyl-4-trifluoromethyl_3,4 · dihydro (1hydro) -quinazolinone (Example 3 2) Separation of XII-b from XII_a (R4 = isopropyl), c using a Chiralpak AD column, 5% water and 95% methanol HPLC at room temperature at a flow rate of 0.5 ml / min and 250 micromm Detection wavelength, can separate the image isomers higher than 100% and 99% of XΠ-b and XII-c, XII-b: mpl55〇C; [a] D25-2.14o (c = 0.280, MeOH) 〇ΧΙΙ-c: mp 98 ° C; [a] D25 + 4.45 ° (c = 0.292, MeOH) 〇 Example 3 3 and 3 4 Preparation of (_) _ 5,6-difluoro-4 -ethylethynyl-4 -Trifluoromethyl-3,4-dihydro (1 氲) Kui Jun _ (Example 3 3) and (+) 5,6 -difluoro-4 -ethylethyl block-4 trifluoromethyl-3,4-dihydro (1 hydrogen) _ p-Quinlinone (Example 3 4) 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 writing this page). Separation of XII-b from XII-a (R4 = ethyl), c Using AS column, 20% Ethanol and 80 hexane HPLC at room temperature can separate the mirror isomers higher than 100% and 99.4% of χπ-b at a flow rate of 1.0 ml / min and a detection wavelength of 250 μm at room temperature. And XII-c, XII_b: mp 165-167 ° C 0 XII-c: mp 157- ° C 159. Example 3 5 and 3 6 -52- This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) 587078 A7 B7 V. Description of the invention (50) Preparation of 5,6 · difluoro_4_ (2_ 经 基Ethyl) ethynyl-4_trifluoromethyl · 3,4 · dihydro (1 hydrogen) -junjunone (Example 35) and 5,6-di, fluoro-4- (1 • Ethylethyl ) Ethyl-4 -trifluoromethyl-3,4 · dihydro (1 hydrogen) -sotriazolinone (Example 30) (Please read the precautions on the back before writing this page)
化合物 範例 35 CH2CH2OH 範例 36 CH (OH)CH3 、1ΤCompound Example 35 CH2CH2OH Example 36 CH (OH) CH3, 1T
« 36 CM(OTBS)CM:i«36 CM (OTBS) CM: i
R 經濟部中央標準局員工消費合作社印製 -78 °C下’依序將遇預冷(〇。〇)之單矽烷基保護炔化鋰 (5.40笔莫耳)及BF3.〇Et2 (0·60毫莫耳)加至内含酮亞胺 (300毫克,1.20毫莫耳)之無水THF (11毫升)粘稠液中, 室溫下隔夜攪拌所得之混合物,添加i M擰檬酸終止反 應’並以EtOAc稀釋,分離相,用水,飽和NaHC〇3水溶 -53 - ^紙張尺度適用中國國家標準(CNS ) 格(21〇><一^^----- 587078 A7 _B7 五、發明説明(54 ) 分析所得:C,52·84 ; Η,3·48 ; Ν,8.80 ;發現:C, 53.02 ; Η, 3.48 ; Ν,8.61。 ' 範例3 8 製備(-)-6 -氯- 4- Ε-環丙基乙块基-4·三氟甲基-3,4 -二氫 -2(1氫)_4峻琳酮 、 根據範例37所述之分法製備標題化合物(自IV-b、起 始),除了 是利用 0.5% EtOH/20% CH2Cl2/79.5% 己烷之 Chirlcel OD管柱純化(流速15毫升/分鐘)。Mp 87-89 °C ; 4 NMR (300 MHz,丙酮 _d6;U 9·08 (br s,1H),7.40-7:25 (m,2H),7.04-6.90 (m,2H),6.28-6.18 (m,1H),5.64-5.52 (m,1H),1.68-1.55 (m,1H),0.83-0.71 (m, 2H),0.53-0.41 (m, 2H) ; 19F NMR (282 MHz,丙酮-d6) $ _81 % . c14h13cif3n2o 計算所得之 ms(ci): m/z 317 066851,發 現 317.065857 ; 317 (MH+,100) ; [a]D2〇 —6 81〇(c==〇 382,R Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs at -78 ° C 'Sequentially pre-cooled (0. 0) mono-silane-protected lithium alkyne (5.40 moll) and BF3.〇Et2 (0 · 60 mmol) was added to a viscous solution containing ketimine (300 mg, 1.20 mmol) in anhydrous THF (11 ml), and the resulting mixture was stirred overnight at room temperature. The reaction was stopped by adding i M citric acid 'And diluted with EtOAc, separated phases, water, saturated NaHC〇3 water-soluble -53-^ paper size applies Chinese National Standard (CNS) grid (21〇 > < 一 ^^ ----- 587078 A7 _B7 V. Description of the invention (54) Analytical results: C, 52.84; H3, 3.48; N, 8.80; Discovery: C, 53.02; H3, 3.48; N, 8.61. 'Example 3 8 Preparation of (-)-6-chlorine -4-E-cyclopropylethyl-4-4 trifluoromethyl-3,4-dihydro-2 (1hydro) -4junlinone, the title compound was prepared according to the method described in Example 37 (from IV -b, start), except that it was purified using a Chirlcel OD column with 0.5% EtOH / 20% CH2Cl2 / 79.5% hexane (flow rate 15 ml / min). Mp 87-89 ° C; 4 NMR (300 MHz, acetone _d6; U 9 · 08 (br s, 1H), 7.40-7: 25 (m, 2H), 7.04-6.90 (m, 2H), 6.28-6.18 (m, 1H), 5.64-5.52 (m, 1H), 1.68-1.55 (m, 1H), 0.83-0.71 (m, 2H) , 0.53-0.41 (m, 2H); 19F NMR (282 MHz, acetone-d6) $ _81%. C14h13cif3n2o Calculated ms (ci): m / z 317 066851, found 317.065857; 317 (MH +, 100); [ a] D2〇-6 81〇 (c == 〇382,
MeOH) ; C14H12C1F3N20 · 0.27C3H6〇 計算分析所得:c 53.52 ; H,4.13 ; N, 8.43 ;發現:C5 53.90 ; H,4 〇7 ’ 8.80 〇 ’ 表1* (請先閱讀背面之注意事項再4-寫本頁) 、-=口 經濟部中央標準局員工消費合作社印製 準 標 家 國 國 中 用 適 度 尺 一張MeOH); C14H12C1F3N20 · 0.27C3H60 Calculated and analyzed: c 53.52; H, 4.13; N, 8.43; Found: C5 53.90; H, 4 〇 7 '8.80 〇' Table 1 * (Please read the precautions on the back and then 4 -Write this page),-= A moderate ruler printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economy
NsNs
587078587078
A B 五、發明説明(55 ) 經濟部中央標準局員工消費合作社印製 範例.# R3 R1 R2 R8 m.p.(°C) 質譜儀 1 6-C1 cf3 C = C-cycPr H 86.6-88 332(M+NH4+) 2 6_C1 cf3 C ^ C-iPr H 180 334(M+NH4+) 3 6-C1 cf3 C = C-2-吡啶基 H 105 352(^) 4 6-C1 cf3 C ^ C-Et H 217-219 303(ΜΗ") 5 6_C1 cf3 C ^ C-Ph H 104-107 368(M+NH4+) 6 6-MeO cf3 C = C-cycPr H 208 311(ΜΗ") 7 6-MeO cf3 C ^ C-iPr H 228-229 3l3(MFt) 8 6-MeO cf3 C Ξ C-2_吡啶基 H 97-98 348(1^) 9 6_MeO cf3 C e 〇Ph H 206.2-207.7 347(ΜΗ") 10 5,6-diF cf3 C = C-cycPr H lOldec 317(MH") 11 5,6-diF cf3 C ^ C-iPr H 79-80 319(ΜΗΓ) 12 5,6-diF cf3 C e C-2-吡啶基 H 219-220 354(ΜΗ") 13 5,6-diF cf3 C = C-Et H 191-194 305(ΜΗ") 14 5,6-diF cf3 C = C-Ph H 215-217 370(M+NH4+) 15 5,6-diF cf3 CH2CH2CH(CH3)2 H 192-193 323(ΜΗ") 16 5,6-diF cf3 CH2CH2CH2CH3 H 309(ΜΗΓ) 17 6-F cf3 C = C-cycPr H 155 299(ΜΗ") 18 6-F cf3 C ^ C-iPr H 158 301(1^) 19 6-F cf3 C e C-2-吡啶基 H 155 336(ΜΗΓ) 20 6-F cf3 C = C-Et H 190 287(ΜΗ") 21 6-F cf3 C = C-Ph H 107 352(Μ+ΝΗ4+) 22 6-F cf3 CH2CH2CH(CH3)2 H 179 305(ΜΗ") -58- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) (請先閱讀背面之注意r項再春寫本頁) 587078AB V. Description of the invention (55) Example of printing by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs. # R3 R1 R2 R8 mp (° C) Mass spectrometer 1 6-C1 cf3 C = C-cycPr H 86.6-88 332 (M + NH4 +) 2 6_C1 cf3 C ^ C-iPr H 180 334 (M + NH4 +) 3 6-C1 cf3 C = C-2-pyridyl H 105 352 (^) 4 6-C1 cf3 C ^ C-Et H 217- 219 303 (ΜΗ ") 5 6_C1 cf3 C ^ C-Ph H 104-107 368 (M + NH4 +) 6 6-MeO cf3 C = C-cycPr H 208 311 (ΜΗ ") 7 6-MeO cf3 C ^ C- iPr H 228-229 3l3 (MFt) 8 6-MeO cf3 C Ξ C-2_pyridylH 97-98 348 (1 ^) 9 6_MeO cf3 C e 〇Ph H 206.2-207.7 347 (ΜΗ ") 10 5, 6-diF cf3 C = C-cycPr H lOldec 317 (MH ") 11 5,6-diF cf3 C ^ C-iPr H 79-80 319 (ΜΗΓ) 12 5,6-diF cf3 C e C-2-pyridine Base H 219-220 354 (ΜΗ ") 13 5,6-diF cf3 C = C-Et H 191-194 305 (ΜΗ ") 14 5,6-diF cf3 C = C-Ph H 215-217 370 (M + NH4 +) 15 5,6-diF cf3 CH2CH2CH (CH3) 2 H 192-193 323 (ΜΗ ") 16 5,6-diF cf3 CH2CH2CH2CH3 H 309 (ΜΗΓ) 17 6-F cf3 C = C-cycPr H 155 299 (ΜΗ ") 18 6-F cf3 C ^ C-iPr H 158 301 (1 ^) 19 6-F cf3 C e C-2-pyridyl H 155 336 (ΜΗΓ) 20 6-F cf3 C = C-Et H 190 287 (ΜΗ ") 21 6-F cf3 C = C-Ph H 107 352 (Μ + ΝΗ4 +) 22 6-F cf3 CH2CH2CH (CH3) 2 H 179 305 (ΜΗ ") -58- This paper size applies to Chinese National Standard (CNS) A4 (210X297 mm) (Please read the note on the back first and write this page in the spring) 587078
7 B 五、發明説明(56 ) 23 6-F cf3 CH2CH2-2-吡啶基 H 88 340(ΜΗ") 24 6-F cf3 ch2ch2ch2ch3 H 198 291(MHT) 25 6-F cf3 CH2CH2Ph H 98 339(^) 26 6-F cf3 ch2c 三 c- ch3 H 181 304(M+NH4+) 27㈠ 6-C1 cf3 C = C-cycPr H 106-109 313(M) 28(+) 6-C1 cf3 C = C-cycPr H 105-107 313(M) 29㈩ 5,6-diF cf3 C = C-cycPr H 187 315(M·) 3〇㈠ 5,6-diF cf3 C = C-cycPr H 188-189 315(MT) 31㈠ 5,6-diF cf3 C = C-iPr H 155 317(M·) 32㈩ 5,6-diF cf3 C ^ C-iPr H 98 317(]Vr) 33㈠ 5,6-diF cf3 C ^ C-Et H 165-167 303(MT) 34(+) 5,6-diF cf3 C ^ C-Et H 157-159 303(M) 35 5,6-diF cf3 C e cch2ch2oh H 190-192 321(ΜΗΓ) 36 5,6-diF cf3 C e C-CH(OH)Me H 190-191 338(M+NH4+) 37㈩ 5,6-diF cf3 C = C-cycPr(E) H 80-83 319(ΜΗ") 38(-) 6-C1 cf3 C = C-cycPr(E) H 87-89 317(ΜΚΓ) *除非特別提及,否則立體化學性是( + /·)。 : _ #II (請先閱讀背面之注意事項再漆寫本頁) 、-口 經濟部中央標準局員工消費合作社印製 -59- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 587078 1 A? B7 五、發明説明(57 ) 表2*7 B V. Description of the invention (56) 23 6-F cf3 CH2CH2-2-pyridyl H 88 340 (ΜΗ ") 24 6-F cf3 ch2ch2ch2ch3 H 198 291 (MHT) 25 6-F cf3 CH2CH2Ph H 98 339 (^ ) 26 6-F cf3 ch2c Triple c- ch3 H 181 304 (M + NH4 +) 27㈠ 6-C1 cf3 C = C-cycPr H 106-109 313 (M) 28 (+) 6-C1 cf3 C = C-cycPr H 105-107 313 (M) 29㈩ 5,6-diF cf3 C = C-cycPr H 187 315 (M ·) 3〇㈠ 5,6-diF cf3 C = C-cycPr H 188-189 315 (MT) 31㈠ 5,6-diF cf3 C = C-iPr H 155 317 (M ·) 32㈩ 5,6-diF cf3 C ^ C-iPr H 98 317 () Vr) 33㈠ 5,6-diF cf3 C ^ C-Et H 165-167 303 (MT) 34 (+) 5,6-diF cf3 C ^ C-Et H 157-159 303 (M) 35 5,6-diF cf3 C e cch2ch2oh H 190-192 321 (ΜΗΓ) 36 5 , 6-diF cf3 C e C-CH (OH) Me H 190-191 338 (M + NH4 +) 37㈩ 5,6-diF cf3 C = C-cycPr (E) H 80-83 319 (ΜΗ ") 38 ( -) 6-C1 cf3 C = C-cycPr (E) H 87-89 317 (ΜΚΓ) * Unless specifically mentioned, the stereochemistry is (+ / ·). : _ #II (Please read the precautions on the back before painting this page) ——- Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economy-59- This paper size applies to the Chinese National Standard (CNS) A4 specification (210X297 mm ) 587078 1 A? B7 V. Description of the invention (57) Table 2 *
經濟部中央標準局員工消費合作社印製Printed by the Staff Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs
範例# R3 R1 R2 R8 1 6-C1 cf3 C^CCH2CH2OH H 2 6-C1 cf3 C^C-CH(OH)Me H 3 6-C1 cf3 C^C-(2-Cl)Ph H 4 6-C1 cf3 C^C-(3-Cl)Ph H 5 6-C1 cf3 ^C^C-(4-Cl)Ph H 6 6_C1 cf3 C^C-(2-F)Ph H 7 6-C1 cf3 C = C-(3-F)Ph H 8 6-C1 cf3 C^C-(4-F)Ph H 9 6-C1 cf3 C^C-(2-OH)Ph H 10 6·α cf3 C = C-(3-OH)Ph H 11 6-C1 cf3 C^C-(4-OH)Ph H 12 6-C1 cf3 C = C-(2-OMe)Ph H 13 6-C1 cf3 C^C-(3-OMe)Ph H 14 6-C1 cf3 C^C-(4-OMe)Ph H 15 6-C1 cf3 C^C-(2-CN)Ph H 16 6-C1 cf3 C^C-(3-CN)Ph H 17 6_C1 cf3 C^C-(4-CN)Ph H 18 6-C1 cf3 C = C-(2-N02)Ph H 19 6-C1 cf3 C^C-(3-N02)Ph H 20 6_C1 cf3 C^C-(4-N02)Ph H 21 6_C1 cf3 C^C-(2-NH2)Ph H 22 6-C1 cf3 C = C-(3-NH2)Ph H 23 6-C1 cf3 C^C-(4-NH2)Ph H (請先閲讀背面之注意事項再餐寫本頁) ίΛ. -60- 本紙張尺度適用中國國家標準(CNS ) A4規格(210'乂 297公’釐) 587078 經濟部中央標準局員工消費合作社印製 A7 五、發明説明(58 )Example # R3 R1 R2 R8 1 6-C1 cf3 C ^ CCH2CH2OH H 2 6-C1 cf3 C ^ C-CH (OH) Me H 3 6-C1 cf3 C ^ C- (2-Cl) Ph H 4 6-C1 cf3 C ^ C- (3-Cl) Ph H 5 6-C1 cf3 ^ C ^ C- (4-Cl) Ph H 6 6_C1 cf3 C ^ C- (2-F) Ph H 7 6-C1 cf3 C = C- (3-F) Ph H 8 6-C1 cf3 C ^ C- (4-F) Ph H 9 6-C1 cf3 C ^ C- (2-OH) Ph H 10 6 · α cf3 C = C- (3-OH) Ph H 11 6-C1 cf3 C ^ C- (4-OH) Ph H 12 6-C1 cf3 C = C- (2-OMe) Ph H 13 6-C1 cf3 C ^ C- (3 -OMe) Ph H 14 6-C1 cf3 C ^ C- (4-OMe) Ph H 15 6-C1 cf3 C ^ C- (2-CN) Ph H 16 6-C1 cf3 C ^ C- (3-CN ) Ph H 17 6_C1 cf3 C ^ C- (4-CN) Ph H 18 6-C1 cf3 C = C- (2-N02) Ph H 19 6-C1 cf3 C ^ C- (3-N02) Ph H 20 6_C1 cf3 C ^ C- (4-N02) Ph H 21 6_C1 cf3 C ^ C- (2-NH2) Ph H 22 6-C1 cf3 C = C- (3-NH2) Ph H 23 6-C1 cf3 C ^ C- (4-NH2) Ph H (Please read the notes on the back before dining and writing this page) ίΛ. -60- This paper size is applicable to China National Standard (CNS) A4 specification (210 '乂 297mm') 587078 Printed by the Consumer Standards Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs A7 V. Invention Description (58)
24 6-C1 cf3 C^C-(2-NMe2)Ph H 25 6-C1 cf3 C^C-(3-NMe2)Ph H 26 6-C1 cf3 C^C-(4-NMe2)Ph H 27 6-C1 cf3 C Ξ C-3-p比喊基 H 28 6-C1 cf3 CeC-4·吡啶基 H 29 6-C1 cf3 C Ξ C-2-咬喃基 H 30 6-C1 cf3 C Ξ C-3-咬喃基 H 31 6-C1 cf3 C^C-2-嘍吩基 H 32 6_C1 cf3 C^C-3-嘧吩基 H 33 6-C1 cf3 Ce〇2-噚唑基 H 34 6-C1 cf3 C^C-2-嘧哇基 H 35 6-C1 cf3 〇C-4-異哼唑基 H 36 6-C1 cf3 Ce〇2-咪唑基 H 37 6-C1 cf3 C=CCH2CH2OH H 38 6-C1 cf3 C=C-CH(OH)Me H 39 6-C1 cf3 C=C-(2-Cl)Ph H 40 6_C1 cf3 C=C-(3-Cl)Ph H 41 6-C1 cf3 C=C_(4-Cl)Ph H 42 6-C1 cf3 C=C-(2-F)Ph H 43 6-C1 cf3 C=C-(3-F)Ph H 44 6-C1 cf3 C=C-(4-F)Ph H 45 6-C1 cf3 C=C-(2-OH)Ph H 46 6-C1 cf3 C=C_(3_OH)Ph H 47 6-C1 cf3 C=C-(4-OH)Ph H 48 6-C1 cf3 C=C-(2-OMe)Ph H 49 6-C1 cf3 C=C-(3-OMe)Ph H 50 6-C1 cf3 C=C-(4-OMe)Ph H 51 6_C1 cf3 C=C-(2-CN)Ph H 52 6-C1 cf3 C=C-(3-CN)Ph H 53 6-C1 cf3 〇C-(4-CN)Ph H (請先閱讀背面之注意事項再务寫本頁) _.61 本紙張尺度適用中國國家標準(CNS ) A4規格(2lOX 297公釐) 587078 A7 B7 五、發明説明(59 ) 經濟部中央標準局員工消費合作社印製 ____k24 6-C1 cf3 C ^ C- (2-NMe2) Ph H 25 6-C1 cf3 C ^ C- (3-NMe2) Ph H 26 6-C1 cf3 C ^ C- (4-NMe2) Ph H 27 6 -C1 cf3 C Ξ C-3-p specific group H 28 6-C1 cf3 CeC-4 · pyridyl H 29 6-C1 cf3 C Ξ C-2-ylanyl H 30 6-C1 cf3 C Ξ C- 3-anilyl H 31 6-C1 cf3 C ^ C-2-fluorenyl H 32 6_C1 cf3 C ^ C-3-pyriminyl H 33 6-C1 cf3 Ce〇2-oxazolyl H 34 6- C1 cf3 C ^ C-2-pyrimidyl H 35 6-C1 cf3 〇C-4-isohumidyl H 36 6-C1 cf3 Ce〇2-imidazolyl H 37 6-C1 cf3 C = CCH2CH2OH H 38 6 -C1 cf3 C = C-CH (OH) Me H 39 6-C1 cf3 C = C- (2-Cl) Ph H 40 6_C1 cf3 C = C- (3-Cl) Ph H 41 6-C1 cf3 C = C_ (4-Cl) Ph H 42 6-C1 cf3 C = C- (2-F) Ph H 43 6-C1 cf3 C = C- (3-F) Ph H 44 6-C1 cf3 C = C- ( 4-F) Ph H 45 6-C1 cf3 C = C- (2-OH) Ph H 46 6-C1 cf3 C = C_ (3_OH) Ph H 47 6-C1 cf3 C = C- (4-OH) Ph H 48 6-C1 cf3 C = C- (2-OMe) Ph H 49 6-C1 cf3 C = C- (3-OMe) Ph H 50 6-C1 cf3 C = C- (4-OMe) Ph H 51 6_C1 cf3 C = C- (2-CN) Ph H 52 6-C1 cf3 C = C- (3-CN) Ph H 53 6-C1 cf3 〇C- (4-CN) Ph H (Please read the back Please note this page to write this page) _.61 This paper size applies to China National Standard (CNS) A4 Grid (2lOX 297 mm) 587078 A7 B7 V. invention is described in (59) Ministry of Economic Affairs Bureau of Standards employees consumer cooperatives printed ____k
54 6-C1 cf3 C=C-(2-N02)Ph H 55 6-C1 cf3 C=C-(3-N02)Ph H 56 6-C1 cf3 C=C_(4_N02)Ph H 57 6-C1 cf3 C=C-(2-NH2)Ph H 58 6_C1 cf3 C=C-(3-NH2)Ph H 59 6-C1 cf3 C=C-(4-NH2)Ph H 60 6_C1 cf3 C=C-(2-NMe2)Ph H 61 6_C1 cf3 C=C-(3-NMe2)Ph H 62 6-C1 cf3 C=C-(4-NMe2)Ph H 63 6-C1 cf3 C=C-3-吡啶基 H 64 6_C1 cf3 OC-4-吡啶基 H 65 6-C1 cf3 C=C-2-呋喃基 H 66 6_C1 cf3 〇C-3-呋喃基 H 67 6-C1 cf3 C=C-2-嘍吩基 H 68 6-C1 cf3 C=C-3-p塞吩基 H 69 6-C1 cf3 C=C-2-呤唑基 H 70 6_C1 cf3 C=C-2^塞唑基 H 71 6-C1 cf3 C=C-4·異哼唑基 H 72 6-C1 cf3 C=C-2-咪唑基 H 73 6_C1 cf3 CH2CH2-cycPr H 74 6_C1 cf3 CH2CH2CH2CH2OH H 75 6-C1 cf3 CH2CH2-CH(OH)Me H 76 6-C1 cf3 CH2CH2-Ph H 77 6-C1 cf3 CH2CH2-(2-Cl)Ph H 78 6-C1 cf3 CH2CH2-(3-Cl)Ph H 79 6-C1 cf3 CH2CH2-(4-Cl)Ph H 80 6-C1 cf3 CH2CHr(2-F)Ph H 81 6_C1 cf3 CH2CH2-(3-F)Ph H 82 6-C1 cf3 CH2CH2-(4-F)Ph H 83 6-C1 cf3 CH2CHr(2-OH)Ph H -62- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X 297公釐) (請先閱讀背面之注意事項再填寫本頁) 訂 587078 經濟部中央標準局員工消費合作社印製 A7 B7 _ 一 五、發明説明() 84 6-C1 cf3 CH2CH2-(3-〇H)Ph H 85 6-C1 cf3 CH2CHr(4-OH)Ph H 86 6-C1 cf3 CH2CHr(2-OMe)Ph H 87 6-C1 cf3 CH2CH2_(3-OMe)Ph H 88 6_C1 cf3 CH2CH2-(4-OMe)Ph H 89 6-C1 cf3 CH2CHr(2-CN)Ph H 90 6-C1 cf3 CH2CHr(3_CN)Ph H 91 6-C1 cf3 CH2CH2-(4-CN)Ph H 92 6_C1 cf3 CH2CH2-(2-N02)Ph H 93 6-C1 cf3 CH2CH2-(3-N02)Ph H 94 6-C1 cf3 CH2CHr(4_N02)Ph H 95 6-C1 cf3 CH2CH2-(2-NH2)Ph H 96 6-C1 cf3 CH2CH2-(3-NH2)Ph H 97 6-C1 cf3 CH2CH2-(4-NH2)Ph H 98 6-C1 cf3 CH2CH2-(2-NMe2)Ph H 99 6-C1 cf3 CH2CHr(3-NMe2)Ph H 100 6-C1 cf3 CH2CH2-(4-NMe2)Ph H 101 6-C1 cf3 CH2CH2-2-吡啶基 H 102 6-C1 cf3 CH2CHr3-吡啶基 H 103 6-C1 cf3 CH2CH2-4-吡啶基 H 104 6-C1 cf3 CH2CHr2-呋喃基 H 105 6_C1 cf3 CH2CH2-3·呋喃基 H 106 6-C1 cf3 CH2CH2-4-呋喃基 H 107 6·α cf3 CH2CH2-3·嘧吩基 H 108 6-C1 cf3 CH2CHr2-噚唑基 H 109 6-C1 cf3 CH2CH2-2-嘍唑基 H 110 6-C1 cf3 CH2CH2-4·異哼唑基 H 111 6-C1 cf3 CH2CHr2-咪唑基 H 112 6-C1 cf3 C = C-cycPr ch3 113 6-C1 cf3 C^C-Ph ch3 -63 - 本紙張尺度適用中國國家標準(CNS ) A4規格(210 X 297公釐) 587078 A7 B7 五、發明説明(61 ) 經濟部中夬標隼局員工消費合作社印製 __I__—k 114 6_C1 cf3 CeC_2-吡啶基 ch3 115 6-C1 cf3 C Ξ C-3-口比淀基 ch3 116 6-C1 cf3 C = C-4-p比淀基 ch3 117 6-C1 cf3 C Ξ C-2·咬喃基 ch3 118 6-C1 cf3 C^C_3-呋喃基 ch3 119 6-C1 cf3 C Ξ C-2-ρ塞吩基 ch3 120 6-C1 cf3 C Ξ C-3-p塞吩基 ch3 121 6-C1 cf3 C=C-cycPr ch3 122 6-C1 cf3 C=C-Ph ch3 123 6-C1 cf3 C=C-2-吡啶基 ch3 124 6-C1 cf3 比咬基 ch3 125 6-C1 cf3 C=C-4-p比淀基 ch3 126 6-C1 cf3 C=C-2-呋喃基 ch3 127 6-C1 cf3 C=C-3-咬喃基 ch3 128 6-C1 cf3 C=C-2-嘧吩基 ch3 129 6-C1 cf3 C=C_3-4 吩基 ch3 130 6-C1 cf3 CH2CH2-cycPr ch3 131 6_C1 cf3 CH2CH2-Ph ch3 132 6_C1 cf3 CH2CH2-2-p 比啶基 ch3 133 6-C1 cf3 CH2CH2-3-吡啶基 ch3 134 6_C1 cf3 CH2CH2-4-吡啶基 ch3 135 6-C1 cf3 CH2CHr2_呋喃基 ch3 136 6-C1 cf3 CH2CH2-3·呋喃基 ch3 137 6-C1 cf3 CH2CHr2-嘧吩基 ch3 138 6_C1 cf3 CH2CH2-3-嘍吩基 ch3 139 6-C1 cf3 C = C-cycPr ch2ch3 140 6-C1 cf3 C^C-Ph CH2CH3 141 6-C1 cf3 CeC-2-吡啶基 ch2ch3 142 6-C1 cf3 CeC_3-口比淀基 CH2CH3 143 6-C1 cf3 C三C-4-口比淀基 ch2ch3 -64- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) (請先閱讀背面之注意事項再填寫本頁) 587078 A7 B7 經濟部中央標準局員工消費合作社印製 五、發明説明(62 ) 1 1 I 144 6-C1 cf3 C Ξ C-2-咬喃基 CH2CH3 1 1 1 145 6-C1 cf3 C = C-3_吱喃基 CH2CH3 1 1 146 6_C1 cf3 C^C-2-嘍吩基 CH2CH3 〆^v 1 請 147 6-C1 cf3 C = C-3-嘍吩基 CH2CH3 先 1 閱 1 148 6-C1 cf3 C=C-cycPr CH2CH3 讀 背-1 jr · 149 6-C1 cf3 C=C-Ph CH2CH3 面 之 150 6·α cf3 比淀基 ch2ch3 1 % ~ 1 151 6-C1 cf3 C=C-3-吡啶基 ch2ch3 事 1 項I 1 152 6·α cf3 C=C-4-p比淀基 ch2ch3 再 1 填-J 寫霞 本7 頁1 N^I 153 6-C1 cf3 C=C-2-呋喃基 CH2CH3 154 6-C1 cf3 C=C_3-呋喃基 CH2CH3 155 6-C1 cf3 C=C-2-嘍吩基 CH2CH3 1 156 6-C1 cf3 C=C-3-p塞吩基 CH2CH3 1 I 157 6-C1 cf3 CH2CH2-cycPr CH2CH3 1 | 158 6-C1 cf3 CH2CH2-Ph CH2CH3 訂 159 6-C1 cf3 CH2CH2-2-吡啶基 CH2CH3 1 160 6-C1 cf3 CH2CH2-3-吡啶基 CH2CH3 1 I 161 6-C1 cf3 CH2CHr4_吡啶基 CH2CH3 1 1 162 6-C1 cf3 CH2CH2_2-呋喃基 CH2CH3 1 163 6-C1 cf3 CH2CH2-3_呋喃基 CH2CH3 1 if .1 164 6-C1 cf3 CH2CHr2-嘍吩基 ch2ch3 165 6-C1 cf3 CH2CHr3-嘧吩基 ch2ch3 166 6-MeO cf3 C = CCH2CH2OH H 167 6-MeO cf3 C = C-CH(OH)Me H 1 168 6-MeO cf3 C^C-(2-Cl)Ph H 1 1 169 6-MeO cf3 C^C-(3-Cl)Ph H 170 6-MeO cf3 C^C-(4-Cl)Ph H 1 1 171 6-MeO cf3 C = C-(2-F)Ph H 1 172 6-MeO cf3 C = C-(3-F)Ph H 1 1 173 6-MeO cf3 C^C-(4-F)Ph -65- H 1 1 1 1 1 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 587078 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明(63 )54 6-C1 cf3 C = C- (2-N02) Ph H 55 6-C1 cf3 C = C- (3-N02) Ph H 56 6-C1 cf3 C = C_ (4_N02) Ph H 57 6-C1 cf3 C = C- (2-NH2) Ph H 58 6_C1 cf3 C = C- (3-NH2) Ph H 59 6-C1 cf3 C = C- (4-NH2) Ph H 60 6_C1 cf3 C = C- (2 -NMe2) Ph H 61 6_C1 cf3 C = C- (3-NMe2) Ph H 62 6-C1 cf3 C = C- (4-NMe2) Ph H 63 6-C1 cf3 C = C-3-pyridyl H 64 6_C1 cf3 OC-4-pyridyl H 65 6-C1 cf3 C = C-2-furanyl H 66 6_C1 cf3 〇C-3-furanyl H 67 6-C1 cf3 C = C-2-fluorenyl H 68 6-C1 cf3 C = C-3-p sedenyl H 69 6-C1 cf3 C = C-2-pyrazolyl H 70 6_C1 cf3 C = C-2 ^ sedazolyl H 71 6-C1 cf3 C = C-4. Isoxazolyl H 72 6-C1 cf3 C = C-2-imidazolyl H 73 6_C1 cf3 CH2CH2-cycPr H 74 6_C1 cf3 CH2CH2CH2CH2OH H 75 6-C1 cf3 CH2CH2-CH (OH) Me H 76 6 -C1 cf3 CH2CH2-Ph H 77 6-C1 cf3 CH2CH2- (2-Cl) Ph H 78 6-C1 cf3 CH2CH2- (3-Cl) Ph H 79 6-C1 cf3 CH2CH2- (4-Cl) Ph H 80 6-C1 cf3 CH2CHr (2-F) Ph H 81 6_C1 cf3 CH2CH2- (3-F) Ph H 82 6-C1 cf3 CH2CH2- (4-F) Ph H 83 6-C1 cf3 CH2CHr (2-OH) Ph H -62- This paper size applies to China National Standard (CNS) A4 (210X 297mm) (Please read first Please fill in this page before filling in this page) Order 587078 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 _15. Invention Description () 84 6-C1 cf3 CH2CH2- (3-〇H) Ph H 85 6-C1 cf3 CH2CHr (4-OH) Ph H 86 6-C1 cf3 CH2CHr (2-OMe) Ph H 87 6-C1 cf3 CH2CH2_ (3-OMe) Ph H 88 6_C1 cf3 CH2CH2- (4-OMe) Ph H 89 6- C1 cf3 CH2CHr (2-CN) Ph H 90 6-C1 cf3 CH2CHr (3_CN) Ph H 91 6-C1 cf3 CH2CH2- (4-CN) Ph H 92 6_C1 cf3 CH2CH2- (2-N02) Ph H 93 6- C1 cf3 CH2CH2- (3-N02) Ph H 94 6-C1 cf3 CH2CHr (4_N02) Ph H 95 6-C1 cf3 CH2CH2- (2-NH2) Ph H 96 6-C1 cf3 CH2CH2- (3-NH2) Ph H 97 6-C1 cf3 CH2CH2- (4-NH2) Ph H 98 6-C1 cf3 CH2CH2- (2-NMe2) Ph H 99 6-C1 cf3 CH2CHr (3-NMe2) Ph H 100 6-C1 cf3 CH2CH2- (4 -NMe2) Ph H 101 6-C1 cf3 CH2CH2-2-pyridyl H 102 6-C1 cf3 CH2CHr3-pyridyl H 103 6-C1 cf3 CH2CH2-4-pyridyl H 104 6-C1 cf3 CH2CHr2-furyl H 105 6_C1 cf3 CH2CH2-3 · furanyl H 106 6-C1 cf3 CH2CH2-4 · furanyl H 107 6 · α cf3 CH2CH2-3 · pyriminyl H 108 6-C1 cf3 CH2CHr2-oxazolyl H 109 6-C1 cf3 CH2CH2-2-oxazolyl H 110 6-C1 cf3 CH2CH2-4 · Isoniazolyl H 111 6-C1 cf3 CH2CHr2-imidazolyl H 112 6-C1 cf3 C = C-cycPr ch3 113 6-C1 cf3 C ^ C-Ph ch3 -63-This paper is for China National Standard (CNS) A4 specification (210 X 297 mm) 587078 A7 B7 V. Description of invention (61) Printed by the Consumers' Cooperative of the China Standards Bureau of the Ministry of Economic Affairs __I __- k 114 6_C1 cf3 CeC_2-pyridyl ch3 115 6 -C1 cf3 C Ξ C-3-Hydro-based ch3 116 6-C1 cf3 C = C-4-p than Yodo-based ch3 117 6-C1 cf3 C Ξ C-2 · Branyl ch3 118 6-C1 cf3 C ^ C_3-furyl ch3 119 6-C1 cf3 C Ξ C-2-ρ sedenyl ch3 120 6-C1 cf3 C Ξ C-3-p sedenyl ch3 121 6-C1 cf3 C = C-cycPr ch3 122 6-C1 cf3 C = C-Ph ch3 123 6-C1 cf3 C = C-2-pyridyl ch3 124 6-C1 cf3 specific group ch3 125 6-C1 cf3 C = C-4-p ratio yodo group ch3 126 6-C1 cf3 C = C-2-furyl ch3 127 6-C1 cf3 C = C-3-pyranyl ch3 128 6-C1 cf3 C = C-2-pyrimyl ch3 129 6-C1 cf3 C = C_3-4 phenyl ch3 130 6-C1 cf3 CH2CH2-cycPr ch3 131 6_C1 cf3 CH2CH2-Ph ch3 132 6_C1 cf3 CH2CH2-2-p than pyridyl ch3 133 6-C1 cf3 CH2CH2-3-pyridyl ch3 134 6_C1 cf3 CH2C H2-4-pyridyl ch3 135 6-C1 cf3 CH2CHr2-furyl ch3 136 6-C1 cf3 CH2CH2-3 · furyl ch3 137 6-C1 cf3 CH2CHr2-pyrimyl ch3 138 6_C1 cf3 CH2CH2-3-fluorenyl ch3 139 6-C1 cf3 C = C-cycPr ch2ch3 140 6-C1 cf3 C ^ C-Ph CH2CH3 141 6-C1 cf3 CeC-2-pyridyl ch2ch3 142 6-C1 cf3 CeC_3-Cyclopyridyl CH2CH3 143 6- C1 cf3 C three C-4-port ratio lake base ch2ch3 -64- This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) (Please read the precautions on the back before filling this page) 587078 A7 B7 Economy Printed by the Consumer Cooperatives of the Ministry of Standards of the People's Republic of China V. Invention Description (62) 1 1 I 144 6-C1 cf3 C Ξ C-2-Branyl CH2CH3 1 1 1 145 6-C1 cf3 C = C-3_ Base CH2CH3 1 1 146 6_C1 cf3 C ^ C-2-fluorenyl CH2CH3 〆 ^ v 1 please 147 6-C1 cf3 C = C-3-fluorenyl CH2CH3 first 1 read 1 148 6-C1 cf3 C = C- cycPr CH2CH3 read back-1 jr · 149 6-C1 cf3 C = C-Ph CH2CH3 150 on the surface 6 · α cf3 1% ~ 1 151 6-C1 cf3 C = C-3-pyridyl ch2ch3 thing 1 The term I 1 152 6 · α cf3 C = C-4-p is more than Yodo base ch2ch3 and then 1 -J write Xia 7 pages 1 N ^ I 153 6-C1 cf3 C = C-2-furyl CH2CH3 154 6-C1 cf3 C = C_3-furyl CH2CH3 155 6-C1 cf3 C = C-2-fluorenyl CH2CH3 1 156 6 -C1 cf3 C = C-3-p sephenyl CH2CH3 1 I 157 6-C1 cf3 CH2CH2-cycPr CH2CH3 1 | 158 6-C1 cf3 CH2CH2-Ph CH2CH3 159 6-C1 cf3 CH2CH2-2-pyridyl CH2CH3 1 160 6-C1 cf3 CH2CH2-3-pyridyl CH2CH3 1 I 161 6-C1 cf3 CH2CHr4-pyridyl CH2CH3 1 1 162 6-C1 cf3 CH2CH2_2-furyl CH2CH3 1 163 6-C1 cf3 CH2CH2-3_furylCH2CH3 1 if .1 164 6-C1 cf3 CH2CHr2-fluorenyl ch2ch3 165 6-C1 cf3 CH2CHr3-pyriminyl ch2ch3 166 6-MeO cf3 C = CCH2CH2OH H 167 6-MeO cf3 C = C-CH (OH) Me H 1 168 6-MeO cf3 C ^ C- (2-Cl) Ph H 1 1 169 6-MeO cf3 C ^ C- (3-Cl) Ph H 170 6-MeO cf3 C ^ C- (4-Cl) Ph H 1 1 171 6-MeO cf3 C = C- (2-F) Ph H 1 172 6-MeO cf3 C = C- (3-F) Ph H 1 1 173 6-MeO cf3 C ^ C- (4-F ) Ph-65- H 1 1 1 1 1 This paper size is applicable to the Chinese National Standard (CNS) A4 (210X297 mm) 587078 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Invention Description (63)
174 6-MeO cf3 C^C-(2-OH)Ph H 175 6_MeO cf3 C^C-(3-OH)Ph H 176 6-MeO cf3 C«4-OH)Ph H 177 6-MeO cf3 C^C-(2-OMe)Ph H 178 6-MeO cf3 C^C-(3-OMe)Ph H 179 6-MeO cf3 C«4-OMe)Ph H 180 6-MeO cf3 C^C-(2-CN)Ph H 181 6-MeO cf3 C^C-(3-CN)Ph H 182 6_MeO cf3 CEC_(4-CN)Ph H 183 6-MeO cf3 C^C-(2-N02)Ph H 184 6-MeO cf3 C 三 C-(3-N02)Ph H 185 6-MeO cf3 C^C-(4-N02)Ph H 186 6-MeO cf3 C 三 C-(2-NH2)Ph H 187 6-MeO cf3 C = C-(3-NH2)Ph H 188 6-MeO cf3 C^C-(4-NH2)Ph H 189 6-MeO cf3 C^C-(2-NMe2)Ph H 190 6-MeO cf3 C^C-(3-NMe2)Ph H 191 6-MeO cf3 C = C-(4-NMe2)Ph H 192 6_MeO cf3 C = C-3-吡啶基 H 193 6-MeO cf3 CeC-4-p比淀基 H 194 6-MeO cf3 C Ξ C-2-咬喃基 H 195 6-MeO CFa C三C-3-吱喃基 H 196 6_MeO cf3 C Ξ C_2-p塞吩基 H 197 6-MeO cf3 C = C-3-嘧吩基 H 198 6-MeO cf3 C = C-2-嘮唑基 H 199 6-MeO cf3 C^C-2-嘧唑基 H 200 6-MeO cf3 C^C-4-異嘮唑基 H 201 6-MeO cf3 C = C-2-咪唑基 H 202 6-MeO cf3 C=CCH2CH2OH H 203 6_MeO cf3 C=C-CH(OH)Me H (請先閱讀背面之注意r項再4-寫本頁)174 6-MeO cf3 C ^ C- (2-OH) Ph H 175 6_MeO cf3 C ^ C- (3-OH) Ph H 176 6-MeO cf3 C «4-OH) Ph H 177 6-MeO cf3 C ^ C- (2-OMe) Ph H 178 6-MeO cf3 C ^ C- (3-OMe) Ph H 179 6-MeO cf3 C «4-OMe) Ph H 180 6-MeO cf3 C ^ C- (2- CN) Ph H 181 6-MeO cf3 C ^ C- (3-CN) Ph H 182 6_MeO cf3 CEC_ (4-CN) Ph H 183 6-MeO cf3 C ^ C- (2-N02) Ph H 184 6- MeO cf3 C tri-C- (3-N02) Ph H 185 6-MeO cf3 C ^ C- (4-N02) Ph H 186 6-MeO cf3 C tri-C- (2-NH2) Ph H 187 6-MeO cf3 C = C- (3-NH2) Ph H 188 6-MeO cf3 C ^ C- (4-NH2) Ph H 189 6-MeO cf3 C ^ C- (2-NMe2) Ph H 190 6-MeO cf3 C ^ C- (3-NMe2) Ph H 191 6-MeO cf3 C = C- (4-NMe2) Ph H 192 6_MeO cf3 C = C-3-pyridylH 193 6-MeO cf3 CeC-4-p H 194 6-MeO cf3 C Ξ C-2-octanoyl H 195 6-MeO CFa C tri-C-3-ananyl H 196 6_MeO cf3 C Ξ C_2-p sephenyl H 197 6-MeO cf3 C = C-3-pyrimylyl H 198 6-MeO cf3 C = C-2-oxazolyl H 199 6-MeO cf3 C ^ C-2-pyrimidyl H 200 6-MeO cf3 C ^ C-4-iso Oxazolyl H 201 6-MeO cf3 C = C-2-imidazolyl H 202 6-MeO cf3 C = CCH2CH2OH H 203 6_MeO cf3 C = C-CH (OH) Me H (Please read the note on the back first r item 4- then write this page)
、1T -66 - 本紙張尺度適用中國國家標準(CNS ) A4規格(210X 297公釐) 587078 經濟部中央標準局員工消費合作社印製 A7 B7 64 五、發明説明() 204 6-MeO cf3 C=C-(2-Cl)Ph Η 205 6_MeO cf3 C=C-(3-Cl)Ph Η 206 6-MeO cf3 C=C_(4-Cl)Ph Η 207 6-MeO cf3 C=C-(2-F)Ph Η 208 6-MeO cf3 C=C-(3-F)Ph Η 209 6-MeO cf3 C=C-(4_F)Ph Η 210 6-MeO cf3 C=C-(2-OH)Ph Η 211 6-MeO cf3 C=C-(3_OH)Ph Η 212 6-MeO cf3 C=C-(4_OH)Ph Η 213 6-MeO cf3 C=C-(2-OMe)Ph Η 214 6-MeO cf3 C=C-(3-OMe)Ph Η 215 6-MeO cf3 OC_(4-OMe)Ph Η 216 6-MeO cf3 C=C-(2-CN)Ph Η 217 6-MeO cf3 C=C-(3-CN)Ph Η 218 6-MeO cf3 C=C-(4-CN)Ph Η 219 6-MeO cf3 C=C-(2_N02)Ph Η 220 6-MeO cf3 C=C-(3-N02)Ph Η 221 6-MeO cf3 C=C-(4-N02)Ph Η 222 6-MeO cf3 C=C-(2-NH2)Ph Η 223 6-MeO cf3 C=C-(3-NH2)Ph Η 224 6-MeO cf3 C=C-(4-NH2)Ph Η 225 6_MeO cf3 C=C-(2-NMe2)Ph Η 226 6-MeO cf3 C=C-(3-NMe2)Ph Η 227 6-MeO cf3 C=C-(4-NMe2)Ph Η 228 6-MeO cf3 C=C-3-'^比淀基 Η 229 6-MeO cf3 C=C-4-p比淀基 Η 230 6-MeO cf3 C=C-2-咬喃基 Η 231 6-MeO cf3 0=C-3-咬喃基 Η 232 6_MeO cf3 C=C-2-p塞吩基 Η 233 6-MeO cf3 C=C-3-嘧吩基 Η -67- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 587078 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明(65 )、 1T -66-This paper size is applicable to Chinese National Standard (CNS) A4 (210X 297mm) 587078 Printed by A7 B7 64, Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention () 204 6-MeO cf3 C = C- (2-Cl) Ph Η 205 6_MeO cf3 C = C- (3-Cl) Ph Η 206 6-MeO cf3 C = C_ (4-Cl) Ph Η 207 6-MeO cf3 C = C- (2- F) Ph 208 208 6-MeO cf3 C = C- (3-F) Ph Η 209 6-MeO cf3 C = C- (4_F) Ph Η 210 6-MeO cf3 C = C- (2-OH) Ph Η 211 6-MeO cf3 C = C- (3_OH) Ph Η 212 6-MeO cf3 C = C- (4_OH) Ph Η 213 6-MeO cf3 C = C- (2-OMe) Ph Η 214 6-MeO cf3 C = C- (3-OMe) Ph Η 215 6-MeO cf3 OC_ (4-OMe) Ph Η 216 6-MeO cf3 C = C- (2-CN) Ph Η 217 6-MeO cf3 C = C- (3 -CN) Ph Η 218 6-MeO cf3 C = C- (4-CN) Ph Η 219 6-MeO cf3 C = C- (2_N02) Ph Η 220 6-MeO cf3 C = C- (3-N02) Ph Η 221 6-MeO cf3 C = C- (4-N02) Ph 222 222 6-MeO cf3 C = C- (2-NH2) Ph Η 223 6-MeO cf3 C = C- (3-NH2) Ph Η 224 6-MeO cf3 C = C- (4-NH2) Ph Η 225 6_MeO cf3 C = C- (2-NMe2) Ph Η 226 6-MeO cf3 C = C- (3-NMe2) Ph Η 227 6-MeO cf3 C = C- (4-NMe2) Ph Η 228 6-MeO cf3 C = C-3-'^ 比 淀 基 Η 229 6-MeO cf3 C = C-4-p 比比Base Η 230 6-MeO cf3 C = C-2-pyranyl Η 231 6-MeO cf3 0 = C-3- 咬 thioyl Η 232 6_MeO cf3 C = C-2-p sephenylΗ 233 6-MeO cf3 C = C-3-pyrimidinyl hydrazone -67- This paper size is applicable to China National Standard (CNS) A4 (210X297 mm) 587078 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Invention Description (65 )
234 6-MeO cf3 C=C-2-哼唑基 H 235 6-MeO cf3 C=C-2_嘍唑基 H 236 6-MeO cf3 C=C-4-異哼唑基 H 237 6-MeO cf3 C=C-2-咪唑基 H 238 6-MeO cf3 CH2CH2-cycPr H 239 6-MeO cf3 CH2CH2CH2CH2〇H H 240 6-MeO cf3 CH2CH2-CH(OH)Me H 241 6-MeO cf3 CH2CH2-Ph H 242 6-MeO cf3 CH2CH2-(2-Cl)Ph H 243 6-MeO cf3 CH2CH2-(3-Cl)Ph H 244 6-MeO cf3 CH2CH2-(4-Cl)Ph H 245 6-MeO cf3 CH2CH2-(2-F)Ph H 246 6-MeO cf3 CH2CH2-(3-F)Ph H 247 6-MeO cf3 CH2CH2-(4-F)Ph H 248 6-MeO cf3 CH2CHr(2-OH)Ph H 249 6-MeO cf3 CH2CH2-(3-〇H)Ph H 250 6-MeO cf3 CH2CH2-(4-OH)Ph H 251 6-MeO cf3 CH2CH2-(2-OMe)Ph H 252 6_MeO cf3 CH2CH2-(3-OMe)Ph H 253 6-MeO cf3 CH2CH2-(4-OMe)Ph H 254 6_MeO cf3 CH2CH2-(2-CN)Ph H 255 6-MeO cf3 CH2CH2-(3-CN)Ph H 256 6-MeO cf3 CH2CHr(4-CN)Ph H 257 6-MeO cf3 CH2CHr(2_N02)Ph H 258 6-MeO cf3 CH2CH2-(3-N02)Ph H 259 6-MeO cf3 CH2CH2-(4-N02)Ph H 260 6-MeO cf3 CH2CH2-(2-NH2)Ph H 261 6-MeO cf3 CH2CH2-(3-NH2)Ph H 262 6_MeO cf3 CH2CH2-(4-NH2)Ph H 263 6-MeO cf3 CH2CHr(2_NMe2)Ph H ----:-----參------1T-------I; (請先閱讀背面之注意r項再4-寫本頁) -68- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 587078 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明(66 ) 264 6-MeO cf3 CH2CH2-(3-NMe2)Ph H 265 6-MeO cf3 CH2CH2-(4-NMe2)Ph H 266 6-MeO cf3 CH2CH2-2-吡啶基 H 267 6_MeO cf3 CH2CH2-3-吡啶基 H 268 6-MeO cf3 CH2CH2-4^比啶基 H 269 6-MeO cf3 CH2CHr2-呋喃基 H 270 6-MeO cf3 CH2CH2-3-呋喃基 H 271 6-MeO cf3 CH2CH2_4-呋喃基 H 272 6-MeO cf3 CH2CHr3-嘍吩基 H 273 6_MeO cf3 CH2CH2-2-噚唑基 H 274 6-MeO cf3 CH2CHr2-嘧唑基 H 275 6_MeO cf3 CH2CH2-4-異嘮唑基 H 276 6-MeO cf3 CH2CH2-2-咪唑基 H 277 6-MeO cf3 C = C-cycPr ch3 278 6_MeO cf3 C^C-Ph ch3 279 6-MeO cf3 C Ξ C-2-p比淀基 ch3 280 6-MeO cf3 OC-3-吡啶基 ch3 281 6-MeO cf3 吡啶基 ch3 282 6-MeO cf3 C = C_2-呋喃基 ch3 283 6_MeO cf3 C Ξ C-3-咬喃基 ch3 284 6-MeO cf3 C = C-2-噻吩基 ch3 285 6_MeO cf3 C = C-3-ρ塞吩基 ch3 286 6-MeO cf3 C=C_cycPr ch3 287 6-MeO cf3 C=C-Ph ch3 288 6-MeO cf3 C=C-2-p比淀基 ch3 289 6-MeO cf3 C=C-3·吡啶基 ch3 290 6_MeO cf3 C=C-4-p比淀基 ch3 291 6-MeO cf3 C=C-2-咬喃基 ch3 292 6_MeO cf3 〇C_3-呋喃基 ch3 293 6-MeO cf3 C=C-2-p塞吩基 ch3 -69- (請先閱讀背面之注意r項再參寫本頁) 4234 6-MeO cf3 C = C-2-humidazolyl H 235 6-MeO cf3 C = C-2_oxazolyl H 236 6-MeO cf3 C = C-4-isohumazolyl H 237 6-MeO cf3 C = C-2-imidazolyl H 238 6-MeO cf3 CH2CH2-cycPr H 239 6-MeO cf3 CH2CH2CH2CH2〇HH 240 6-MeO cf3 CH2CH2-CH (OH) Me H 241 6-MeO cf3 CH2CH2-Ph H 242 6-MeO cf3 CH2CH2- (2-Cl) Ph H 243 6-MeO cf3 CH2CH2- (3-Cl) Ph H 244 6-MeO cf3 CH2CH2- (4-Cl) Ph H 245 6-MeO cf3 CH2CH2- (2 -F) Ph H 246 6-MeO cf3 CH2CH2- (3-F) Ph H 247 6-MeO cf3 CH2CH2- (4-F) Ph H 248 6-MeO cf3 CH2CHr (2-OH) Ph H 249 6-MeO cf3 CH2CH2- (3-〇H) Ph H 250 6-MeO cf3 CH2CH2- (4-OH) Ph H 251 6-MeO cf3 CH2CH2- (2-OMe) Ph H 252 6_MeO cf3 CH2CH2- (3-OMe) Ph H 253 6-MeO cf3 CH2CH2- (4-OMe) Ph H 254 6_MeO cf3 CH2CH2- (2-CN) Ph H 255 6-MeO cf3 CH2CH2- (3-CN) Ph H 256 6-MeO cf3 CH2CHr (4- CN) Ph H 257 6-MeO cf3 CH2CHr (2_N02) Ph H 258 6-MeO cf3 CH2CH2- (3-N02) Ph H 259 6-MeO cf3 CH2CH2- (4-N02) Ph H 260 6-MeO cf3 CH2CH2- (2-NH2) Ph H 261 6-MeO cf3 CH2CH2- (3-NH2) Ph H 262 6_MeO cf3 CH2CH2- (4-NH2) Ph H 263 6-MeO cf3 CH2CHr (2_NMe2) Ph H ----:- - --Refer to ------- 1T ------- I; (Please read the note r on the back before writing 4-page) -68- This paper size applies to China National Standard (CNS) A4 (210X297 mm) 587078 Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Invention Description (66) 264 6-MeO cf3 CH2CH2- (3-NMe2) Ph H 265 6-MeO cf3 CH2CH2- (4-NMe2 ) Ph H 266 6-MeO cf3 CH2CH2-2-pyridyl H 267 6_MeO cf3 CH2CH2-3-pyridyl H 268 6-MeO cf3 CH2CH2-4 ^ pyridyl H 269 6-MeO cf3 CH2CHr2-furyl H 270 6 -MeO cf3 CH2CH2-3-furanyl H 271 6-MeO cf3 CH2CH2_4-furyl H 272 6-MeO cf3 CH2CHr3-fluorenyl H 273 6_MeO cf3 CH2CH2-2-oxazolyl H 274 6-MeO cf3 CH2CHr2-pyrimidine Azolyl H 275 6_MeO cf3 CH2CH2-4-isoxazolyl H 276 6-MeO cf3 CH2CH2-2-imidazolyl H 277 6-MeO cf3 C = C-cycPr ch3 278 6_MeO cf3 C ^ C-Ph ch3 279 6- MeO cf3 C Ξ C-2-p than Yodoyl ch3 280 6-MeO cf3 OC-3-pyridyl ch3 281 6-MeO cf3 pyridyl ch3 282 6-MeO cf3 C = C_2-furyl ch3 283 6_MeO cf3 C Ξ C-3-branyl ch3 284 6-MeO cf3 C = C-2-thienyl ch3 285 6_MeO cf3 C = C- 3-ρ sephenyl ch3 286 6-MeO cf3 C = C_cycPr ch3 287 6-MeO cf3 C = C-Ph ch3 288 6-MeO cf3 C = C-2-p than yodoyl ch3 289 6-MeO cf3 C = C-3 · pyridyl ch3 290 6_MeO cf3 C = C-4-p ratio than yl ch3 291 6-MeO cf3 C = C-2-pyranyl ch3 292 6_MeO cf3 〇C_3-furyl ch3 293 6-MeO cf3 C = C-2-p sephenyl ch3 -69- (Please read the note of r on the back before writing this page) 4
、1T 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 587078 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明(67 ) 294 6_MeO cf3 C=C-3-嘧吩基 ch3 295 6_MeO cf3 CH2CH2-cycPr ch3 296 6-MeO cf3 CH2CHrPh ch3 297 6-MeO cf3 CH2CH2-2-毗啶基 ch3 298 6-MeO cf3 CH2CH2_3-吡啶基 ch3 299 6-MeO cf3 CH2CH2-4-吡啶基 ch3 300 6_MeO cf3 CH2CH2-2-呋喃基 ch3 301 6-MeO cf3 CH2CH2-3-呋喃基 ch3 302 6_MeO cf3 CH2CH2-2_嘧吩基 ch3 303 6-MeO cf3 CH2CH2-3·嘧吩基 ch3 304 6_MeO cf3 C = C-cycPr ch2ch3 305 6-MeO cf3 C^C-Ph CH2CH3 306 6-MeO cf3 C Ξ C_2-p比淀基 CH2CH3 307 6-MeO cf3 C Ξ 03-峨淀基 CH2CH3 308 6-MeO cf3 C e C-4w比淀基 CH2CH3 309 6-MeO cf3 C = C_2-呋喃基 CH2CH3 310 6-MeO cf3 C = C-3-吱喃基 ch2ch3 311 6-MeO cf3 CeC-2-嘧吩基 CH2CH3 312 6-MeO cf3 C Ξ C_3_p塞吩基 CH2CH3 313 6-MeO cf3 C=C-cycPr CH2CH3 314 6-MeO cf3 C=C-Ph CH2CH3 315 6-MeO cf3 C=C-2-吡啶基 ch2ch3 316 6-MeO cf3 C=C-3-吡啶基 CH2CH3 317 6-MeO cf3 C=C-4-吡啶基 CH2CH3 318 6-MeO cf3 C=C-2-呋喃基 ch2ch3 319 6-MeO cf3 C=C_3-呋喃基 CH2CH3 320 6-MeO cf3 C=C-2-嘍吩基 ch2ch3 321 6-MeO cf3 C=C-3-嘧吩基 CH2CH3 322 6-MeO cf3 CH2CH2-cycPr ch2ch3 323 6-MeO cf3 CH2CH2-Ph CH2CH3 (請先閱讀背面之注意r項再4-寫本頁) -70- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 587078 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明(68 ) 324 6-MeO cf3 CH2CHr2-吡啶基 CH2CH3 1 325 6-MeO cf3 CH2CH2-3-吡啶基 CH2CH3 1 326 6-MeO cf3 CH2CHr4-吡啶基 CH2CH3 請 先1 閱 1 讀 背Ί 面 | 之 塋1 r丨 2 1 再 1 填-J 寫 本7 百 327 6-MeO cf3 CH2CH2-2-呋喃基 CH2CH3 328 6-MeO cf3 CH2CH2-3-呋喃基 ch2ch3 329 6-MeO cf3 CH2CH2-2-嚙吩基 ch2ch3 330 6-MeO cf3 CH2CH2-3-嘍吩基 CH2CH3 331 5,6_diF cf3 C = C-(2-Cl)Ph H 332 5,6-diF cf3 C = C-(3_Cl)Ph H 333 5,6-diF cf3 C«4-Cl)Ph H 334 5,6-diF cf3 C = C-(2-F)Ph H Xs 1 -^ I 335 5,6-diF cf3 C^C-(3-F)Ph H 1 I 336 5,6-diF cf3 C = C-(4-F)Ph H 1 I 337 5,6-diF cf3 C = C-(2-OH)Ph H 1 1 338 5,6-diF cf3 C^C-(3-OH)Ph H 訂 339 5,6-diF cf3 C = C-(4-OH)Ph H 1 I 340 5,6-diF cf3 C^C-(2-OMe)Ph H 1 I 341 5,6-diF cf3 C^C-(3-OMe)Ph H 1 1 342 5,6-diF cf3 C^C-(4-OMe)Ph H 1 I 343 5,6-diF cf3 CEC-(2-CN)Ph H 1 4 344 5,6-diF cf3 C = C-(3-CN)Ph H 345 5,6-diF cf3 C^C-(4-CN)Ph H j 346 5,6-diF cf3 C^C-(2-N02)Ph H I 347 5,6-diF cf3 C^C-(3-N02)Ph H 1 348 5,6-diF cf3 CEC_(4-N02)Ph H 1 1 349 5,6-diF cf3 C^C-(2-NH2)Ph H 350 5,6-diF cf3 C^C-(3-NH2)Ph H 1 I 351 5,6-diF cf3 C^C-(4-NH2)Ph H I 352 5,6-diF cf3 C^C-(2-NMe2)Ph H 1 353 5,6-diF cf3 CEC-(3-NMe2)Ph H 1 -71 - 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 587078 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明(69 )、 1T This paper size applies to Chinese National Standard (CNS) A4 specification (210X297 mm) 587078 Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs A7 B7 V. Description of the invention (67) 294 6_MeO cf3 C = C-3-pyrimidine Ch3 295 6_MeO cf3 CH2CH2-cycPr ch3 296 6-MeO cf3 CH2CHrPh ch3 297 6-MeO cf3 CH2CH2-2-pyridyl ch3 298 6-MeO cf3 CH2CH2_3-pyridyl ch3 299 6-MeO cf3 CH2CH2-4-pyridyl ch3 300 6_MeO cf3 CH2CH2-2-furyl ch3 301 6-MeO cf3 CH2CH2-3-furyl ch3 302 6_MeO cf3 CH2CH2-2_pyrimyl ch3 303 6-MeO cf3 CH2CH2-3 · pyrimyl ch3 304 6_MeO cf3 C = C-cycPr ch2ch3 305 6-MeO cf3 C ^ C-Ph CH2CH3 306 6-MeO cf3 C Ξ C_2-p than Yodo CH2CH3 307 6-MeO cf3 C Ξ 03-EYODO CH2CH3 308 6-MeO cf3 C e C-4w ratio Yodo CH2CH3 309 6-MeO cf3 C = C_2-furanyl CH2CH3 310 6-MeO cf3 C = C-3-creanyl ch2ch3 311 6-MeO cf3 CeC-2-pyridinyl CH2CH3 312 6 -MeO cf3 C Ξ C_3_p sephenyl CH2CH3 313 6-MeO cf3 C = C-cycPr CH2CH3 314 6-MeO cf3 C = C-Ph CH2CH3 315 6-MeO cf3 C = C-2-pyridyl ch2ch3 316 6-MeO cf3 C = C-3- Pyridyl CH2CH3 317 6-MeO cf3 C = C-4-pyridyl CH2CH3 318 6-MeO cf3 C = C-2-furyl ch2ch3 319 6-MeO cf3 C = C_3-furyl CH2CH3 320 6-MeO cf3 C = C-2-fluorenyl ch2ch3 321 6-MeO cf3 C = C-3-pyridinyl CH2CH3 322 6-MeO cf3 CH2CH2-cycPr ch2ch3 323 6-MeO cf3 CH2CH2-Ph CH2CH3 (Please read the note on the back first (Further, write this page) -70- This paper size is in accordance with Chinese National Standard (CNS) A4 (210X297 mm) 587078 Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs A7 B7 V. Invention Description (68) 324 6- MeO cf3 CH2CHr2-pyridyl CH2CH3 1 325 6-MeO cf3 CH2CH2-3-pyridyl CH2CH3 1 326 6-MeO cf3 CH2CHr4-pyridyl CH2CH3 Please read 1 first 1 read back | tomb 1 r 丨 2 1 again 1 Fill-J book 7 hundred 327 6-MeO cf3 CH2CH2-2-furyl CH2CH3 328 6-MeO cf3 CH2CH2-3-furyl ch2ch3 329 6-MeO cf3 CH2CH2-2-pyridyl ch2ch3 330 6-MeO cf3 CH2CH2- 3-fluorenyl CH2CH3 331 5,6_diF cf3 C = C- (2-Cl) Ph H 332 5,6-diF cf3 C = C- (3_Cl) Ph H 333 5,6-diF cf3 C «4-Cl ) Ph H 334 5,6-diF cf3 C = C- (2-F) Ph H Xs 1-^ I 335 5,6-diF cf3 C ^ C- (3-F) Ph H 1 I 336 5,6-diF cf3 C = C- (4-F) Ph H 1 I 337 5,6-diF cf3 C = C- (2-OH) Ph H 1 1 338 5,6-diF cf3 C ^ C- (3-OH) Ph H 339 5,6-diF cf3 C = C- (4-OH) Ph H 1 I 340 5 , 6-diF cf3 C ^ C- (2-OMe) Ph H 1 I 341 5,6-diF cf3 C ^ C- (3-OMe) Ph H 1 1 342 5,6-diF cf3 C ^ C- ( 4-OMe) Ph H 1 I 343 5,6-diF cf3 CEC- (2-CN) Ph H 1 4 344 5,6-diF cf3 C = C- (3-CN) Ph H 345 5,6-diF cf3 C ^ C- (4-CN) Ph H j 346 5,6-diF cf3 C ^ C- (2-N02) Ph HI 347 5,6-diF cf3 C ^ C- (3-N02) Ph H 1 348 5,6-diF cf3 CEC_ (4-N02) Ph H 1 1 349 5,6-diF cf3 C ^ C- (2-NH2) Ph H 350 5,6-diF cf3 C ^ C- (3-NH2 ) Ph H 1 I 351 5,6-diF cf3 C ^ C- (4-NH2) Ph HI 352 5,6-diF cf3 C ^ C- (2-NMe2) Ph H 1 353 5,6-diF cf3 CEC -(3-NMe2) Ph H 1 -71-This paper size applies to Chinese National Standard (CNS) A4 (210X297 mm) 587078 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Invention Description (69)
354 5,6-diF cf3 C^C-(4-NMe2)Ph H 355 5,6_diF cf3 C = 〇3-吡啶基 H 356 5,6-diF cf3 CeC-4-峨淀基 H 357 5,6-diF cf3 C = 02-吱喃基 H 358 5,6-diF cf3 C Ξ C-3-咬喃基 H 359 5,6-diF cf3 C = C-2-嘧吩基 H 360 5,6-diF cf3 C Ξ C-3-p塞吩基 H 361 5,6-diF cf3 CeC-2-崎唑基 H 362 5,6-diF cf3 C = C-2-嘧唑基 H 363 5,6-diF cf3 C^C-4-異嘮唑基 H 364 5,6-diF cf3 C = C-2-咪唑基 H 365 5,6-diF cf3 C=C-(2-Cl)Ph H 366 5,6-diF cf3 C=C-(3-Cl)Ph H 367 5,6-diF cf3 C=C-(4-Cl)Ph H 368 5,6-diF cf3 C=C-(2-F)Ph H 369 5,6-diF cf3 C=C-(3-F)Ph H 370 5,6-diF cf3 C=C-(4-F)Ph H 371 5,6-diF cf3 C=C_(2-OH)Ph H 372 5,6-diF cf3 C=C-(3-OH)Ph H 373 5,6-diF cf3 C=C-(4-OH)Ph H 374 5,6-diF cf3 C=C-(2-OMe)Ph H 375 5,6-diF cf3 C=C-(3-OMe)Ph H 376 5,6-diF cf3 C=C-(4-OMe)Ph H 377 5,6-diF cf3 C=C-(2-CN)Ph H 378 5,6-diF cf3 C=C-(3-CN)Ph H 379 5,6-diF cf3 C=C_(4-CN)Ph H 380 5,6-diF cf3 C=C-(2-N02)Ph H 381 5,6-diF cf3 C=C-(3-N02)Ph H 382 5,6-diF cf3 C=C-(4-N02)Ph H 383 5,6-diF cf3 C=C-(2-NH2)Ph H -72- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 587078 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明(% )354 5,6-diF cf3 C ^ C- (4-NMe2) Ph H 355 5,6_diF cf3 C = 〇3-pyridylH 356 5,6-diF cf3 CeC-4-Eodoyl H 357 5,6 -diF cf3 C = 02-creanyl H 358 5,6-diF cf3 C Ξ C-3-octanoyl H 359 5,6-diF cf3 C = C-2-pyridinyl H 360 5,6- diF cf3 C Ξ C-3-p sedenyl H 361 5,6-diF cf3 CeC-2-azazolyl H 362 5,6-diF cf3 C = C-2-pyrazolyl H 363 5,6- diF cf3 C ^ C-4-isoxazolyl H 364 5,6-diF cf3 C = C-2-imidazolyl H 365 5,6-diF cf3 C = C- (2-Cl) Ph H 366 5, 6-diF cf3 C = C- (3-Cl) Ph H 367 5,6-diF cf3 C = C- (4-Cl) Ph H 368 5,6-diF cf3 C = C- (2-F) Ph H 369 5,6-diF cf3 C = C- (3-F) Ph H 370 5,6-diF cf3 C = C- (4-F) Ph H 371 5,6-diF cf3 C = C_ (2- OH) Ph H 372 5,6-diF cf3 C = C- (3-OH) Ph H 373 5,6-diF cf3 C = C- (4-OH) Ph H 374 5,6-diF cf3 C = C -(2-OMe) Ph H 375 5,6-diF cf3 C = C- (3-OMe) Ph H 376 5,6-diF cf3 C = C- (4-OMe) Ph H 377 5,6-diF cf3 C = C- (2-CN) Ph H 378 5,6-diF cf3 C = C- (3-CN) Ph H 379 5,6-diF cf3 C = C_ (4-CN) Ph H 380 5, 6-diF cf3 C = C- (2-N02) Ph H 381 5,6-diF cf3 C = C- (3-N02) Ph H 382 5,6-diF cf3 C = C- (4-N02) Ph H 383 5,6-diF cf3 C = C- (2-NH2) Ph H -72- This paper size is applicable to China National Standard (CNS) A4 (210X297 mm) 587078 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention (%)
384 5,6-diF cf3 C=C-(3-NH2)Ph H 385 5,6-diF cf3 C=C-(4-NH2)Ph H 386 5,6-diF cf3 C=C-(2-NMe2)Ph H 387 5,6-diF cf3 C=C-(3-NMe2)Ph H 388 5,6-diF cf3 C=C-(4-NMe2)Ph H 389 5,6-diF cf3 C=C-3-峨淀基 H 390 5,6-diF cf3 比淀基 H 391 5,6-diF cf3 C=C-2-咬喃基 H 392 5,6-diF cf3 C=C-3_呋喃基 H 393 5,6-diF cf3 OC-2-嘧吩基 H 394 5,6-diF cf3 C=C-3-p塞吩基 H 395 5,6-diF cf3 C=C-2-崎哇基 H 396 5,6-diF cf3 C=C-2-嘧唑基 H 397 5,6-diF cf3 OC-4-異嘮唑基 H 398 5,6-diF cf3 C=C-2-咪唑基 H 399 5,6-diF cf3 CH2CH2-cycPr H 400 5,6-diF cf3 CH2CH2CH2CH2OH H 401 5,6-diF cf3 CH2CH2-CH(OH)Me H 402 5,6-diF cf3 CH2CH2-Ph H 403 5,6-diF cf3 CH2CH2-(2-Cl)Ph H 404 5,6-diF cf3 CH2CH2-(3-Cl)Ph H 405 5,6-diF cf3 CH2CH2-(4-Cl)Ph H 406 5,6-diF cf3 CH2CH2-(2-F)Ph H 407 5,6-diF cf3 CH2CH2-(3-F)Ph H 408 5,6-diF cf3 CH2CH2-(4-F)Ph H 409 5,6-diF cf3 CH2CH2-(2-OH)Ph H 440 5,6-diF cf3 CH2CH2-(3.〇H)Ph H 411 5,6-diF cf3 CH2CH2-(4-OH)Ph H 412 5,6-diF cf3 CH2CH2-(2-OMe)Ph H 413 5,6-diF cf3 CH2CH2-(3-〇Me)Ph H -73- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 587078 經濟部中央標準局員工消費合作社印製 Μ Β7 71 — 五、發明説明() 414 5,6-diF cf3 CH2CH2-(4-OMe)Ph H 415 5,6_diF cf3 CH2CH2-(2-CN)Ph H 416 5,6-diF cf3 CH2CH2-(3-CN)Ph H 417 5,6-diF cf3 CH2CH2-(4-CN)Ph H 418 5,6-diF cf3 CH2CH2-(2-N02)Ph H 419 5,6-diF cf3 CH2CHr(3-N02)Ph H 420 5,6-diF cf3 CH2CH2-(4-N02)Ph H 421 5,6-diF cf3 CH2CH2-(2-NH2)Ph H 422 5,6-diF cf3 CH2CH2-(3-NH2)Ph H 423 5,6-diF cf3 CH2CHr(4_NH2)Ph H 424 5,6-diF cf3 CH2CH2_(2-NMe2)Ph H 425 5,6-diF cf3 CH2CH2-(3-NMe2)Ph H 426 5,6-diF cf3 CH2CHr(4-NMe2)Ph H 427 5,6-diF cf3 CH2CHr2·吡啶基 H 428 5,6-diF cf3 CH2CHr3-吡啶基 H 429 5,6-diF cf3 CH2CH2-4-吡啶基 H 430 5,6-diF cf3 CH2CHr2-呋喃基 H 431 5,6-diF cf3 CH2CHr3-呋喃基 H 432 5,6-diF cf3 CH2CH2-2-嘧吩基 H 433 5,6-diF cf3 CH2CH2-3^塞吩基 H 434 5,6-diF cf3 CH2CH2_2-嘮唑基 H 435 5,6-diF cf3 CH2CH2-2-嘍唑基 H 436 5,6-diF cf3 CH2CH2_4-異嘮唑基 H 437 5,6-diF cf3 CH2CH2_2_咪唑基 H 438 5,6-diF cf3 C = C-cycPr ch3 439 5,6-diF cf3 CeC-2-吡啶基 ch3 440 5,6-diF cf3 CeC_3·吡啶基 ch3 441 5,6-diF cf3 CeC_4-说淀基 ch3 442 5,6-diF cf3 C Ξ C-2-咬喃基 ch3 443 5,6-diF cf3 C Ξ C-3-咬喃基 ch3 -74- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 587078 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明(72 ) 444 5,6-diF cf3 C = C-2-ρ塞吩基 ch3 445 5,6-diF cf3 C = C-3-p塞吩基 ch3 446 5,6-diF cf3 C=C-cycPr ch3 ,^v 請 閱 讀 背 面 意 事- 項 再 填- 寫 本 百 447 5,6-diF cf3 C=C-2-p比淀基 ch3 448 5,6-diF cf3 C=C-3-吡啶基 ch3 449 5,6-diF cf3 C=C-4-p比淀基 ch3 450 5,6-diF cf3 C=C-2-咬喃基 ch3 451 5,6-diF cf3 C=C-3-咬喃基 ch3 452 5,6-diF CFs C=C-2-嘧吩基 ch3 453 5,6-diF cf3 C=C-3-嘍吩基 ch3 454 5,6-diF cf3 CH2CH2-cycPr ch3 月 455 5,6-diF cf3 CH2CH2-Ph ch3 456 5,6-diF cf3 CH2CH2-2·吡啶基 ch3 457 5,6-diF cf3 CH2CH2-3-吡啶基 ch3 458 5,6-diF cf3 CH2CH2-4-吡啶基 ch3 459 5,6-diF cf3 CH2CHr2-呋喃基 ch3 460 5,6-diF cf3 CH2CH2-3-呋喃基 ch3 461 5,6-diF cf3 CH2CHr2-嘍吩基 ch3 462 5,6-diF cf3 CH2CH2_3_嘍吩基 ch3 463 5,6-diF cf3 C^C-cycPr . CH2CH3 464 5,6-diF cf3 C^C-Ph CH2CH3 465 5,6-diF cf3 C Ξ C-2-p比途基 CH2CH3 466 5,6-diF cf3 Ce〇3-吡啶基 CH2CH3 467 5,6-diF cf3 c=c斗吡啶基 CH2CH3 468 5,6-diF cf3 C Ξ C-2-咬喃基 CH2CH3 469 5,6-diF cf3 C Ξ C-3-咬喃基 ch2ch3 470 5,6-diF cf3 C Ξ C-2-遠吩基 CH2CH3 471 5,6-diF cf3 C Ξ C-3-p塞吩基 CH2CH3 472 5,6-diF cf3 C=C-cycPr CH2CH3 473 5,6-diF cf3 C=C-Ph CH2CH3 -75- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 587078 經濟部中央標準局員工消費合作社印裂 A7 B7 五、發明説明(73 )384 5,6-diF cf3 C = C- (3-NH2) Ph H 385 5,6-diF cf3 C = C- (4-NH2) Ph H 386 5,6-diF cf3 C = C- (2- NMe2) Ph H 387 5,6-diF cf3 C = C- (3-NMe2) Ph H 388 5,6-diF cf3 C = C- (4-NMe2) Ph H 389 5,6-diF cf3 C = C -3-Edoyl H 390 5,6-diF cf3 than Yodo H 391 5,6-diF cf3 C = C-2-octanoyl H 392 5,6-diF cf3 C = C-3_furanyl H 393 5,6-diF cf3 OC-2-pyridinyl H 394 5,6-diF cf3 C = C-3-p cephenyl H 395 5,6-diF cf3 C = C-2-zawalyl H 396 5,6-diF cf3 C = C-2-pyrazolyl H 397 5,6-diF cf3 OC-4-isoxazolyl H 398 5,6-diF cf3 C = C-2-imidazolyl H 399 5,6-diF cf3 CH2CH2-cycPr H 400 5,6-diF cf3 CH2CH2CH2CH2OH H 401 5,6-diF cf3 CH2CH2-CH (OH) Me H 402 5,6-diF cf3 CH2CH2-Ph H 403 5,6 -diF cf3 CH2CH2- (2-Cl) Ph H 404 5,6-diF cf3 CH2CH2- (3-Cl) Ph H 405 5,6-diF cf3 CH2CH2- (4-Cl) Ph H 406 5,6-diF cf3 CH2CH2- (2-F) Ph H 407 5,6-diF cf3 CH2CH2- (3-F) Ph H 408 5,6-diF cf3 CH2CH2- (4-F) Ph H 409 5,6-diF cf3 CH2CH2 -(2-OH) Ph H 440 5,6-diF cf3 CH2CH2- (3.〇H) Ph H 411 5,6-diF cf3 CH2CH2- (4-OH) Ph H 412 5,6-diF cf3 CH2CH2- (2-OMe) Ph H 413 5, 6-diF cf3 CH2CH2- (3-〇Me) Ph H -73- This paper size applies to China National Standard (CNS) A4 (210X297 mm) 587078 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs Β7 71 — 5 Description of the invention () 414 5,6-diF cf3 CH2CH2- (4-OMe) Ph H 415 5,6_diF cf3 CH2CH2- (2-CN) Ph H 416 5,6-diF cf3 CH2CH2- (3-CN) Ph H 417 5,6-diF cf3 CH2CH2- (4-CN) Ph H 418 5,6-diF cf3 CH2CH2- (2-N02) Ph H 419 5,6-diF cf3 CH2CHr (3-N02) Ph H 420 5 , 6-diF cf3 CH2CH2- (4-N02) Ph H 421 5,6-diF cf3 CH2CH2- (2-NH2) Ph H 422 5,6-diF cf3 CH2CH2- (3-NH2) Ph H 423 5,6 -diF cf3 CH2CHr (4_NH2) Ph H 424 5,6-diF cf3 CH2CH2_ (2-NMe2) Ph H 425 5,6-diF cf3 CH2CH2- (3-NMe2) Ph H 426 5,6-diF cf3 CH2CHr (4 -NMe2) Ph H 427 5,6-diF cf3 CH2CHr2-pyridyl H 428 5,6-diF cf3 CH2CHr3-pyridyl H 429 5,6-diF cf3 CH2CH2-4-pyridyl H 430 5,6-diF cf3 CH2CHr2-furanyl H 431 5,6-diF cf3 CH2CHr3-furanyl H 432 5,6-diF cf3 CH2CH2-2-pyridinyl H 433 5,6-diF cf3 CH2CH2-3 ^ sedenyl H 434 5, 6-diF cf3 CH2CH2_2-oxazolyl H 435 5,6-diF cf3 CH2CH2-2 -Oxazolyl H 436 5,6-diF cf3 CH2CH2_4-isoxazolyl H 437 5,6-diF cf3 CH2CH2_2_imidazolyl H 438 5,6-diF cf3 C = C-cycPr ch3 439 5,6-diF cf3 CeC-2-pyridyl ch3 440 5,6-diF cf3 CeC_3 · pyridyl ch3 441 5,6-diF cf3 CeC_4-saidyl ch3 442 5,6-diF cf3 C Ξ C-2-pyranyl ch3 443 5,6-diF cf3 C Ξ C-3-branyl ch3 -74- This paper size is applicable to China National Standard (CNS) A4 (210X297 mm) 587078 Printed by A7, Consumer Cooperative of the Central Standards Bureau, Ministry of Economic Affairs V. Description of the invention (72) 444 5,6-diF cf3 C = C-2-ρ sephenyl ch3 445 5,6-diF cf3 C = C-3-p sephenyl ch3 446 5,6-diF cf3 C = C-cycPr ch3, ^ v Please read the notice on the back-fill in the entries-write a hundred hundred 447 5,6-diF cf3 C = C-2-p than Yodo ch3 448 5,6-diF cf3 C = C- 3-pyridyl ch3 449 5,6-diF cf3 C = C-4-p than yodoyl ch3 450 5,6-diF cf3 C = C-2-ylanyl ch3 451 5,6-diF cf3 C = C -3-Oranyl ch3 452 5,6-diF CFs C = C-2-pyridinyl ch3 453 5,6-diF cf3 C = C-3-fluorenyl ch3 454 5,6-diF cf3 CH2CH2- cycPr ch3 May 455 5,6-diF cf3 CH2CH2-Ph ch3 456 5, 6-diF cf3 CH2CH2-2 · pyridyl ch3 457 5,6-diF cf3 CH2CH2-3-pyridyl ch3 458 5,6-diF cf3 CH2CH2-4-pyridyl ch3 459 5,6-diF cf3 CH2CHr2-furyl ch3 460 5,6-diF cf3 CH2CH2-3-furyl ch3 461 5,6-diF cf3 CH2CHr2-fluorenyl ch3 462 5,6-diF cf3 CH2CH2_3_fluorenyl ch3 463 5,6-diF cf3 C ^ C-cycPr. CH2CH3 464 5,6-diF cf3 C ^ C-Ph CH2CH3 465 5,6-diF cf3 C Ξ C-2-p than the base CH2CH3 466 5,6-diF cf3 Ce〇3-pyridyl CH2CH3 467 5,6-diF cf3 c = c-pyridyl group CH2CH3 468 5,6-diF cf3 C Ξ C-2-ylpyranyl CH2CH3 469 5,6-diF cf3 C Ξ C-3-pyranyl ch2ch3 470 5 , 6-diF cf3 C Ξ C-2-distenyl CH2CH3 471 5,6-diF cf3 C Ξ C-3-p sephenyl CH2CH3 472 5,6-diF cf3 C = C-cycPr CH2CH3 473 5,6 -diF cf3 C = C-Ph CH2CH3 -75- This paper size applies to Chinese National Standard (CNS) A4 (210X297 mm) 587078 Employees' Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs printed A7 B7 V. Description of the invention (73)
474 5,6-diF cf3 C=C-2-p比淀基 CH2CH3 475 5,6_diF cf3 C=C-3-吡啶基 CH2CH3 476 5,6-diF cf3 C=C-4-p比淀基 CH2CH3 -V 請 477 5,6-diF cf3 C=C_2-呋喃基 CH2CH3 先 閱 478 5,6-diF cf3 C=C-3·呋喃基 CH2CH3 讀 背 479 5,6-diF cf3 C=C-2-p塞吩基 CH2CH3 面 之 480 5,6-diF cf3 C=C-3-p塞吩基 ch2ch3 >王 意 481 5,6-diF cf3 CH2CH2-cycPr ch2ch3 爭 項 482 5,6-diF cf3 CH2CH2-Ph CH2CH3 丹 填- 483 5,6-diF cf3 CH2CH2-2-吡啶基 CH2CH3 本 百 484 5,6-diF cf3 CH2CH2-3-吡啶基 CH2CH3 貝 485 5,6-diF cf3 CH2CH2_4-吡啶基 ch2ch3 486 5,6-diF cf3 CH2CH2-2-呋喃基 CH2CH3 487 5,6-diF cf3 CH2CHr3-呋喃基 CH2CH3 488 5,6-diF cf3 CH2CH2-2-嘧吩基 ch2ch3 489 5,6-diF cf3 CH2CH2-3-嘧吩基 CH2CH3 490 5,6-diCl cf3 C^C-(2-Cl)Ph H 491 5,6-diCl cf3 C^C-(3-Cl)Ph H 492 5,6-diCl cf3 C^C-(4-Cl)Ph H 493 5,6-diCl cf3 C^C-(2-F)Ph H 494 5,6-diCl cf3 C^C-(3-F)Ph H 495 5,6-diCl cf3 C^C-(4-F)Ph H 496 5,6-diCl cf3 CeC-(2-OH)Ph H 497 5,6-diCl cf3 C^C-(3-OH)Ph H 498 5,6-diCl cf3 C^C-(4-OH)Ph H 499 5,6-diCl cf3 C^C-(2-OMe)Ph H 500 5,6-diCl cf3 C^C-(3-OMe)Ph H 501 5,6-diCl cf3 〇C-(4-OMe)Ph H 502 5,6-diCl cf3 C^C-(2-CN)Ph H 503 5,6-diCl cf3 C^C-(3-CN)Ph H -76- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 587078 經濟部中央標準局員工消費合作社印製 kl B7 74 五、發明説明() 504 5,6-diCl cf3 C^C-(4-CN)Ph H 讎 1 505 5,6-diCl cf3 C^C-(2-N02)Ph H 1 506 5,6-diCl cf3 C^C-(3-N02)Ph H I 請 507 5,6-diCl cf3 C«4_N02)Ph H I 閱 1 508 5,6-diCl cf3 C^C-(2-NH2)Ph H 讀 背Ί 509 5,6-diCl cf3 C^C-(3-NH2)Ph H 面 1 510 5,6-diCl cf3 C = C-(4-NH2)Ph H t、 古- 1 511 5,6-diCl cf3 C^C-(2-NMe2)Ph H 事 i 2 1 512 5,6-diCl cf3 C 三 C_(3-NMe2)Ph H 513 5,6-diCl cf3 C^C-(4-NMe2)Ph H 514 5,6-diCl cf3 Ce〇3-吡啶基 H 頁 1 515 5,6-diCl cf3 C Ξ C_4-外匕淀基 H 1 1 516 5,6-diCl cf3 C = C-2-咬喃基 H 1 I 517 5,6-diCl cf3 C = C-3-咬喃基 H 1 I 518 5,6-diCl cf3 C^C-2-嘍吩基 H 1 訂 519 5,6-diCl cf3 C = C-3-噻吩基 H 1 520 5,6-diCl cf3 C = C-2-嘮唑基 H 1 I 521 5,6-diCl cf3 C^C-2-嘍唑基 H 1 | 522 5,6-diCl cf3 OC-4-異嘮唑基 H 1 523 5,6-diCl cf3 C = C-2-咪唑基 H 1 524 5,6-diCl cf3 C=C - (2-Cl)Ph H 1 525 5,6-diCl cf3 C=C-(3-Cl)Ph H 1 526 5,6-diCl cf3 C=C-(4-Cl)Ph H Ί 527 5,6-diCl cf3 C=C-(2-F)Ph H 1 528 5,6-diCl cf3 C=C-(3-F)Ph H _l 1 529 5,6-diCl cf3 C=C-(4-F)Ph H 530 5,6-diCl cf3 C=C-(2-OH)Ph H 1 I 531 5,6-diCl cf3 C=C-(3-OH)Ph H I 532 5,6-diCl cf3 C=C-(4-OH)Ph H 1 1 533 5,6-diCl cf3 C=C-(2-OMe)Ph H 1 -77- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X 297公釐) 587078 經濟部中央標準局員工消費合作社印製 Μ Β7 五、發明説明(75 )474 5,6-diF cf3 C = C-2-p ratio Yodo CH2CH3 475 5,6_diF cf3 C = C-3-pyridyl CH2CH3 476 5,6-diF cf3 C = C-4-p ratio Yodo CH2CH3 -V Please read 477 5,6-diF cf3 C = C_2-furyl CH2CH3 First read 478 5,6-diF cf3 C = C-3 · furyl CH2CH3 Read back 479 5,6-diF cf3 C = C-2- p-Cyphenyl CH2CH3 480 5,6-diF cf3 C = C-3-p-Cyphenyl ch2ch3 > Wang Yi 481 5,6-diF cf3 CH2CH2-cycPr ch2ch3 contention 482 5,6-diF cf3 CH2CH2 -Ph CH2CH3 Danfill- 483 5,6-diF cf3 CH2CH2-2-pyridylCH2CH3 Benzene 484 5,6-diF cf3 CH2CH2-3-pyridyl CH2CH3 485 5,6-diF cf3 CH2CH2_4-pyridyl ch2ch3 486 5,6-diF cf3 CH2CH2-2-furyl CH2CH3 487 5,6-diF cf3 CH2CHr3-furyl CH2CH3 488 5,6-diF cf3 CH2CH2-2-pyrimyl ch2ch3 489 5,6-diF cf3 CH2CH2-3 -Pyrimidinyl CH2CH3 490 5,6-diCl cf3 C ^ C- (2-Cl) Ph H 491 5,6-diCl cf3 C ^ C- (3-Cl) Ph H 492 5,6-diCl cf3 C ^ C- (4-Cl) Ph H 493 5,6-diCl cf3 C ^ C- (2-F) Ph H 494 5,6-diCl cf3 C ^ C- (3-F) Ph H 495 5,6- diCl cf3 C ^ C- (4-F) Ph H 496 5,6-diCl cf3 CeC- (2-OH) Ph H 497 5,6-diCl cf3 C ^ C- (3-OH) Ph H 498 5,6-diCl cf3 C ^ C- (4-OH) Ph H 499 5,6-diCl cf3 C ^ C- (2-OMe) Ph H 500 5,6-diCl cf3 C ^ C- (3 -OMe) Ph H 501 5,6-diCl cf3 〇C- (4-OMe) Ph H 502 5,6-diCl cf3 C ^ C- (2-CN) Ph H 503 5,6-diCl cf3 C ^ C -(3-CN) Ph H -76- This paper size applies to Chinese National Standard (CNS) A4 (210X297 mm) 587078 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs kl B7 74 V. Description of Invention () 504 5 , 6-diCl cf3 C ^ C- (4-CN) Ph H 雠 1 505 5,6-diCl cf3 C ^ C- (2-N02) Ph H 1 506 5,6-diCl cf3 C ^ C- (3 -N02) Ph HI Please 507 5,6-diCl cf3 C «4_N02) Ph HI Read 1 508 5,6-diCl cf3 C ^ C- (2-NH2) Ph H Read back 509 5,6-diCl cf3 C ^ C- (3-NH2) Ph H surface 1 510 5,6-diCl cf3 C = C- (4-NH2) Ph H t, ancient-1 511 5,6-diCl cf3 C ^ C- (2-NMe2 ) Ph H matter 2 1 512 5,6-diCl cf3 C tri-C_ (3-NMe2) Ph H 513 5,6-diCl cf3 C ^ C- (4-NMe2) Ph H 514 5,6-diCl cf3 Ce 〇3-PyridylH Page 1 515 5,6-diCl cf3 C Ξ C_4-Exopyridyl H 1 1 516 5,6-diCl cf3 C = C-2-Branyl H 1 I 517 5,6- diCl cf3 C = C-3-branyl H 1 I 518 5,6-diCl cf3 C ^ C-2-fluorenyl H 1 order 519 5,6-diCl cf3 C = C-3-thienyl H 1 520 5,6-diCl cf3 C = C-2-oxazolyl H 1 I 521 5,6-diCl cf3 C ^ C-2 -Oxazolyl H 1 | 522 5,6-diCl cf3 OC-4-isooxazolyl H 1 523 5,6-diCl cf3 C = C-2-imidazolyl H 1 524 5,6-diCl cf3 C = C-(2-Cl) Ph H 1 525 5,6-diCl cf3 C = C- (3-Cl) Ph H 1 526 5,6-diCl cf3 C = C- (4-Cl) Ph H Ί 527 5 , 6-diCl cf3 C = C- (2-F) Ph H 1 528 5,6-diCl cf3 C = C- (3-F) Ph H _l 1 529 5,6-diCl cf3 C = C- (4 -F) Ph H 530 5,6-diCl cf3 C = C- (2-OH) Ph H 1 I 531 5,6-diCl cf3 C = C- (3-OH) Ph HI 532 5,6-diCl cf3 C = C- (4-OH) Ph H 1 1 533 5,6-diCl cf3 C = C- (2-OMe) Ph H 1 -77- This paper size applies Chinese National Standard (CNS) A4 specification (210X 297 (Mm) 587078 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs Β7. Invention Description (75)
534 5,6-diCl cf3 OC_(3-OMe)Ph H 535 5,6-diCl cf3 C=C-(4-OMe)Ph H 536 5,6-diCl cf3 C=C-(2-CN)Ph H 537 5,6_diCl cf3 C=C-(3-CN)Ph H 538 5,6-diCl cf3 C=C-(4-CN)Ph H 539 5,6-diCl cf3 C=C-(2-N02)Ph H 540 5,6-diCl cf3 C=C-(3-N02)Ph H 541 5,6-diCl cf3 C=C-(4-NO:j)Ph H 542 5,6-diCl cf3 C=C-(2-NH2)Ph H 543 5,6-diCl cf3 C=C-(3-NH2)Ph H 544 5,6-diCl cf3 C=C-(4-NH2)Ph H 545 5,6-diCl cf3 C=C-(2-NMe2)Ph H 546 5,6-diCl cf3 C=C-(3-NMe2)Ph H 547 5,6-diCl cf3 OC_(4_NMe2)Ph H 548 5,6-diCl cf3 C=C-3-p比淀基 H 549 5,6-diCl cf3 C=C-4-#b 淀基 H 550 5,6-diCl cf3 C=C-2-咬喃基 H 551 5,6-diCl cf3 C=C-3-咬喃基 H 552 5,6-diCl cf3 C=C-2-^ 吩基 H 553 5,6-diCl cf3 C=C-3-p塞吩基 H 554 5,6-diCl cf3 亏哇基 H 555 5,6-diCl cf3 C=C-2-嘧唑基 H 556 5,6-diCl cf3 C=C-4-異嘮唑基 H 557 5,6-diCl cf3 C=C-2-咪唑基 H 558 5,6-diCl cf3 CH2CH2-cycPr H 559 5,6-diCl cf3 CH2CH2CH2CH2OH H 560 5,6-diCl cf3 CH2CH2-CH(OH)Me H 561 5,6-diCl cf3 CH2CH2-Ph H 562 5,6-diCl cf3 CH2CH2-(2-Cl)Ph H 563 5,6-diCl cf3 CH2CHr(3-Cl)Ph H (請先閱讀背面之注意事項再4-寫本頁) "口 -73- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X 297公釐) 587078 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明(76 )534 5,6-diCl cf3 OC_ (3-OMe) Ph H 535 5,6-diCl cf3 C = C- (4-OMe) Ph H 536 5,6-diCl cf3 C = C- (2-CN) Ph H 537 5,6_diCl cf3 C = C- (3-CN) Ph H 538 5,6-diCl cf3 C = C- (4-CN) Ph H 539 5,6-diCl cf3 C = C- (2-N02 ) Ph H 540 5,6-diCl cf3 C = C- (3-N02) Ph H 541 5,6-diCl cf3 C = C- (4-NO: j) Ph H 542 5,6-diCl cf3 C = C- (2-NH2) Ph H 543 5,6-diCl cf3 C = C- (3-NH2) Ph H 544 5,6-diCl cf3 C = C- (4-NH2) Ph H 545 5,6- diCl cf3 C = C- (2-NMe2) Ph H 546 5,6-diCl cf3 C = C- (3-NMe2) Ph H 547 5,6-diCl cf3 OC_ (4_NMe2) Ph H 548 5,6-diCl cf3 C = C-3-p ratio Yodo H 549 5,6-diCl cf3 C = C-4- # b Yodo H 550 5,6-diCl cf3 C = C-2-Oranyl H 551 5, 6-diCl cf3 C = C-3-octanoyl H 552 5,6-diCl cf3 C = C-2- ^ phenyl H 553 5,6-diCl cf3 C = C-3-p cephenyl H 554 5,6-diCl cf3 owayl H 555 5,6-diCl cf3 C = C-2-pyrazolyl H 556 5,6-diCl cf3 C = C-4-isooxazolyl H 557 5,6- diCl cf3 C = C-2-imidazolyl H 558 5,6-diCl cf3 CH2CH2-cycPr H 559 5,6-diCl cf3 CH2CH2CH2CH2OH H 560 5,6-diCl cf3 CH2CH2-CH (OH) Me H 561 5,6 -diCl cf3 CH2CH2-Ph H 562 5,6-diCl cf3 CH2CH2- (2-Cl) P h H 563 5,6-diCl cf3 CH2CHr (3-Cl) Ph H (Please read the precautions on the back before 4-writing this page) " 口 -73- This paper size applies to China National Standard (CNS) A4 specifications (210X 297 mm) 587078 A7 B7 printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs 5. Description of the invention (76)
564 5,6-diCl cf3 CH2CH2-(4-Cl)Ph H 565 5,6-diCl cf3 CH2CH2-(2-F)Ph H 566 5,6-diCl cf3 CH2CHr(3-F)Ph H 567 5,6-diCl cf3 CH2CH2-(4-F)Ph H 568 5,6-diCl cf3 CH2CH2-(2-OH)Ph H 569 5,6-diCl cf3 CH2CH2-(3-〇H)Ph H 570 5,6-diCl cf3 CH2CH2-(4-OH)Ph H 571 5,6-diCl cf3 CH2CH2-(2-OMe)Ph H 572 5,6-diCl cf3 CH2CH2-(3-OMe)Ph H 573 5,6-diCl cf3 CH2CH2-(4-OMe)Ph H 574 5,6-diCl cf3 CH2CH2-(2-CN)Ph H 575 5,6-diCl cf3 CH2CH2-(3-CN)Ph H 576 5,6-diCl cf3 CH2CH2-(4-CN)Ph H 577 5,6-diCl cf3 CH2CH2_(2-N02)Ph H 578 5,6-diCl cf3 CH2CH2-(3-N02)Ph H 579 5,6-diCl cf3 CH2CH2-(4-N02)Ph H 580 5,6-diCl cf3 CH2CH2-(2-NH2)Ph H 581 5,6-diCl cf3 CH2CH2-(3-NH2)Ph H 582 5,6-diCl cf3 CH2CH2-(4-NH2)Ph H 583 5,6-diCl cf3 CH2CH2-(2-NMe2)Ph H 584 5,6-diCl cf3 CH2CH2-(3-NMe2)Ph . H 585 5,6-diCl cf3 CH2CH2-(4-NMe2)Ph H 586 5,6-diCl cf3 CH2CHr2-吡啶基 H 587 5,6-diCl cf3 CH2CHr3-吡啶基 H 588 5,6-diCl cf3 CH2CH2-4-此啶基 H 589 5,6-diCl cf3 CH2CH2-2-呋喃基 H 590 5,6-diCl cf3 CH2CHr3-呋喃基 H 591 5,6-diCl cf3 CH2CH2-2-噻吩基 H 592 5,6-diCl cf3 CH2CHr3-嘧吩基 H 593 5,6-diCl cf3 CH2CHr2-嘮唑基 H -79- (請先閱讀背面之注意•事項再4-寫本頁)564 5,6-diCl cf3 CH2CH2- (4-Cl) Ph H 565 5,6-diCl cf3 CH2CH2- (2-F) Ph H 566 5,6-diCl cf3 CH2CHr (3-F) Ph H 567 5, 6-diCl cf3 CH2CH2- (4-F) Ph H 568 5,6-diCl cf3 CH2CH2- (2-OH) Ph H 569 5,6-diCl cf3 CH2CH2- (3-〇H) Ph H 570 5,6 -diCl cf3 CH2CH2- (4-OH) Ph H 571 5,6-diCl cf3 CH2CH2- (2-OMe) Ph H 572 5,6-diCl cf3 CH2CH2- (3-OMe) Ph H 573 5,6-diCl cf3 CH2CH2- (4-OMe) Ph H 574 5,6-diCl cf3 CH2CH2- (2-CN) Ph H 575 5,6-diCl cf3 CH2CH2- (3-CN) Ph H 576 5,6-diCl cf3 CH2CH2 -(4-CN) Ph H 577 5,6-diCl cf3 CH2CH2_ (2-N02) Ph H 578 5,6-diCl cf3 CH2CH2- (3-N02) Ph H 579 5,6-diCl cf3 CH2CH2- (4 -N02) Ph H 580 5,6-diCl cf3 CH2CH2- (2-NH2) Ph H 581 5,6-diCl cf3 CH2CH2- (3-NH2) Ph H 582 5,6-diCl cf3 CH2CH2- (4-NH2 ) Ph H 583 5,6-diCl cf3 CH2CH2- (2-NMe2) Ph H 584 5,6-diCl cf3 CH2CH2- (3-NMe2) Ph. H 585 5,6-diCl cf3 CH2CH2- (4-NMe2) Ph H 586 5,6-diCl cf3 CH2CHr2-pyridyl H 587 5,6-diCl cf3 CH2CHr3-pyridyl H 588 5,6-diCl cf3 CH2CH2-4-this pyridyl H 589 5,6-diCl cf3 CH2CH2- 2-furyl H 590 5,6-diCl cf3 CH2CHr3-furyl H 5 91 5,6-diCl cf3 CH2CH2-2-thienyl H 592 5,6-diCl cf3 CH2CHr3-pyrimyl H 593 5,6-diCl cf3 CH2CHr2-oxazolyl H -79- (Please read the note on the back first • Matters again 4- write this page)
、1T 本紙張尺度適用中國國家標準(CNS ) A4規格(210X 297公釐) 587078 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明(77 ) 594 5,6-diCl cf3 CH2CHr2-嘧唑基 H 595 5,6-diCl cf3 CH2CH2-4-異嘮唑基 H 596 5,6-diCl cf3 CH2CHr2-咪唑基 H 請 597 5,6-diCl cf3 C = C-cycPr ch3 先 閱 士 598 5,6_diCl cf3 C Ξ C-2-p比淀基 ch3 項 背 599 5,6-diCl cf3 C e C_3-p比淀基 ch3 面 之 600 5,6-diCl cf3 CeC-4_吡啶基 ch3 注 意 古 601 5,6-diCl cf3 C Ξ C-2-咬喃基 ch3 事 項 602 5,6-diCl cf3 C Ξ C-3·咬喃基 ch3 再 填 603 5,6-diCl cf3 C Ξ C-2-p塞吩基 ch3 本 百 604 5,6-diCl cf3 C Ξ C-3-p塞吩基 ch3 貝 605 5,6-diCl cf3 C=C-cycPr ch3 606 5,6-diCl cf3 C=C-2-吡啶基 ch3 607 5,6-diCl cf3 C=C-3 比淀基 ch3 608 5,6-diCl cf3 比淀基 ch3 609 5,6-diCl cf3 C=C-2-咬喃基 ch3 610 5,6-diCl cf3 C=C-3-咬喃基 ch3 611 5,6-diCl cf3 C=C-2-p塞吩基 ch3 612 5,6-diCl cf3 C=C-3-p塞吩基 ch3 613 5,6-diCl cf3 CH2CH2-cycPr ch3 614 5,6-diCl cf3 CH2CH2-Ph ch3 615 5,6-diCl cf3 CH2CHr2-吡啶基 ch3 616 5,6-diCl cf3 • CH2CHr3-吡啶基 ch3 617 5,6-diCl cf3 CH2CH2-4-吡啶基 ch3 618 5,6-diCl cf3 CH2CH2-2·呋喃基 ch3 619 5,6-diCl cf3 CH2CH2-3·呋喃基 ch3 620 5,6-diCl cf3 CH2CH2-2-嘍吩基 ch3 621 5,6-diCl cf3 CH2CH2-3_嘍吩基 ch3 622 5,6-diCl cf3 C = C-cycPr ch2ch3 623 5,6-diCl cf3 C^C-Ph ch2ch3 -80- 本紙張尺度適用中國國家標準(CNS ) A4規格(210 X 297公釐) 587078 經濟部中央標準局員工消費合作社印製 Μ Β7 78 五、發明説明()、 1T This paper size is applicable to Chinese National Standard (CNS) A4 specification (210X 297 mm) 587078 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention (77) 594 5,6-diCl cf3 CH2CHr2-pyrimide Azolyl H 595 5,6-diCl cf3 CH2CH2-4-isoxazolyl H 596 5,6-diCl cf3 CH2CHr2-imidazolyl H Please 597 5,6-diCl cf3 C = C-cycPr ch3 Read 598 5 , 6_diCl cf3 C Ξ C-2-p is more than the base ch3 term 599 5,6-diCl cf3 C e C_3-p is 600 than the surface of the base ch3 5,6-diCl cf3 CeC-4_pyridyl ch3 Note the ancient 601 5,6-diCl cf3 C Ξ C-2-Oranyl ch3 602 5,6-diCl cf3 C Ξ C-3 · Orano ch3 Refill 603 5,6-diCl cf3 C Ξ C-2- p-Cephenyl ch3 Benzene 604 5,6-diCl cf3 C Ξ C-3-p-Cephenyl ch3 Bay 605 5,6-diCl cf3 C = C-cycPr ch3 606 5,6-diCl cf3 C = C- 2-pyridyl ch3 607 5,6-diCl cf3 C = C-3 than yl ch3 608 5,6-diCl cf3 than yl ch3 609 5,6-diCl cf3 C = C-2-pyranyl ch3 610 5,6-diCl cf3 C = C-3-octanoyl ch3 611 5,6-diCl cf3 C = C-2-p-sedenyl ch3 612 5,6-diCl cf3 C = C-3-p-sedyl Ch3 613 5,6-di Cl cf3 CH2CH2-cycPr ch3 614 5,6-diCl cf3 CH2CH2-Ph ch3 615 5,6-diCl cf3 CH2CHr2-pyridyl ch3 616 5,6-diCl cf3 • CH2CHr3-pyridyl ch3 617 5,6-diCl cf3 CH2CH2 -4-pyridyl ch3 618 5,6-diCl cf3 CH2CH2-2 · furyl ch3 619 5,6-diCl cf3 CH2CH2-3 · furyl ch3 620 5,6-diCl cf3 CH2CH2-2-fluorenyl ch3 621 5,6-diCl cf3 CH2CH2-3_fluorenyl ch3 622 5,6-diCl cf3 C = C-cycPr ch2ch3 623 5,6-diCl cf3 C ^ C-Ph ch2ch3 -80- This paper size applies to Chinese national standards (CNS) A4 specification (210 X 297 mm) 587078 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs Β7 78 V. Description of the invention ()
624 5,6-diCl cf3 C = C-2-吡啶基 CH2CH3 625 5,6-diCl cf3 CeC-3_p比皮基 CH2CH3 626 5,6-diCl cf3 C Ξ C-4-p比淀基 ch2ch3 627 5,6-diCl cf3 C^C-2-呋喃基 CH2CH3 628 5,6-diCl cf3 C = C-3-吱喃基 CH2CH3 629 5,6-diCl cf3 C = C-2-噻吩基 CH2CH3 630 5,6-diCl cf3 C^C-3-嘍吩基 CH2CH3 631 5,6-diCl cf3 C=C-cycPr CH2CH3 632 5,6-diCl cf3 C=C-Ph ch2ch3 633 5,6-diCl cf3 C=C-2-吡啶基 ch2ch3 634 5,6-diCl cf3 C=C-3_p比淀基 CH2CH3 635 5,6-diCl cf3 C=C_4_峨淀基 ch2ch3 636 5,6-diCl cf3 C=C-2_呋喃基 ch2ch3 637 5,6-diCl cf3 C=C-3-咬喃基 ch2ch3 638 5,6-diCl cf3 C=C-2-p塞吩基 CH2CH3 639 5,6-diCl cf3 C=C-3-p塞吩基 ch2ch3 640 5,6-diCl cf3 CH2CH2-cycPr CH2CH3 641 5,6-diCl cf3 CH2CHrPh CH2CH3 642 5,6-diCl cf3 CH2CHr2-吡啶基 ch2ch3 643 5,6-diCl cf3 CH2CH2-3-吡啶基 CH2CH3 644 5,6-diCl cf3 CH2CHr4-吡啶基 CH2CH3 645 5,6-diCl cf3 CH2CH2_2_呋喃基 ch2ch3 646 5,6-diCl cf3 CH2CHr3-呋喃基 CH2CH3 647 5,6-diCl cf3 CH2CH2-2-p塞吩基 CH2CH3 648 5,6-diCl cf3 CH2CH2-3-嘍吩基 CH2CH3 649 6-F cf3 C^CCH2CH2OH H 650 6_F cf3 OC-CH(OH)Me H 651 6-F cf3 C^C-(2-Cl)Ph H 652 6-F cf3 C = C-(3-Cl)Ph H 653 6-F cf3 C^C-(4-Cl)Ph H (請先閱讀背面之注意•事項再填寫本頁) 、1Τ -81 - 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 587078 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明(79 ) 654 6_F cf3 C = C-(2-F)Ph Η 655 6-F cf3 C^C-(3-F)Ph Η 656 6-F cf3 C^C-(4-F)Ph Η 657 6-F cf3 C = C-(2_OH)Ph Η 658 6-F cf3 C^C-(3-OH)Ph Η 659 6-F cf3 C^C-(4-OH)Ph Η 660 6-F cf3 C^C-(2-OMe)Ph Η 661 6-F cf3 C«3_OMe)Ph Η 662 6-F cf3 C = C-(4-OMe)Ph Η 663 6-F cf3 C^C-(2-CN)Ph Η 664 6-F cf3 C^C-(3-CN)Ph Η 665 6-F cf3 C^C-(4-CN)Ph Η 666 6-F cf3 CEC-(2-N02)Ph Η 667 6-F cf3 C^C-(3-N02)Ph Η 668 6-F cf3 C^C-(4-N02)Ph Η 669 6-F cf3 C 三 C-(2-NH2)Ph Η 670 6-F cf3 C^C-(3-NH2)Ph Η 671 6-F cf3 C 三 C-(4-NH2)Ph Η 672 6-F cf3 C^C-(2-NMe2)Ph Η 673 6-F cf3 C^C-(3-NMe2)Ph Η 674 6-F cf3 C^C-(4-NMe2)Ph Η 675 6-F cf3 CeC-3-p比淀基 Η 676 6-F cf3 C三C-4-口比喝:基 Η 677 6-F cf3 C^C-2-吱喃基 Η 678 6_F cf3 C Ξ C-3-咬喃基 Η 679 6-F cf3 C^C-2-嘧吩基 Η 680 6-F cf3 C Ξ C-3-遠吩基 Η 681 6-F cf3 Ce〇2-嘮唑基 Η 682 6-F cf3 C = C-2-嘧唑基 Η 683 6-F cf3 C^C-4-異哼唑基 Η -82- (請先閲讀背面之注意r項再填寫本頁) 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 587078 A7 B7 五、發明説明(8Q ) 經濟部中央標準局員工消費合作社印製 684 6-F cf3 C = C-2-咪峻基 H 1 1 685 6-F cf3 C=CCH2CH2OH H 1 I 686 6-F cf3 C=C-CH(OH)Me H 1 請 先1 閱 1 讀 背-1 面 I 之 1 · r 1 項 1 fd 687 6-F cf3 C=C-(2-Cl)Ph H 688 6-F cf3 C=C_(3_Cl)Ph H 689 6-F cf3 C=C-(4-Cl)Ph H 690 6-F cf3 C=C-(2-F)Ph H 691 6-F cf3 C=C-(3-F)Ph H 692 6-F cf3 C=C-(4-F)Ph H 693 6-F cf3 C=C-(2-OH)Ph H 本^ 百 694 6-F cf3 C=C-(3-OH)Ph H 月 1 ν^ I 695 6-F cf3 C=C-(4-OH)Ph H 1 696 6_F cf3 C=C-(2-OMe)Ph H 1 I 697 6-F cf3 C=C-(3-OMe)Ph H 1 I 698 6-F cf3 C=C-(4-OMe)Ph H 訂 699 6-F cf3 C=C-(2-CN)Ph H 1 I 700 6-F cf3 C=C-(3-CN)Ph H 1 I 701 6-F cf3 C=C-(4-CN)Ph H 1 1 702 6-F cf3 C=C-(2-N02)Ph H 1 I 703 6-F cf3 C=C-(3-N02)Ph H 1 704 6-F cf3 C=C-(4-N02)Ph H 705 6-F cf3 C=C-(2-NH2)Ph H J 706 6-F cf3 C=C-(3-NH2)Ph H 707 6-F cf3 OC-(4-NH2)Ph H 1 708 6-F cf3 C=C-(2-NMe2)Ph H 1 1 709 6-F cf3 OC-(3_NMe2)Ph H 710 6-F cf3 C=C-(4-NMe2)Ph H 1 1 711 6-F cf3 0=0-3-0比淀基 H I 712 6-F cf3 C=C-4-吡啶基 H 1 1 713 6-F cf3 C=C-2-咬喃基 -83 - H 1 1 1 1 1 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 587078 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明(81 ) 714 6_F cf3 C=C-3-咬喃基 H 1 715 6-F cf3 C=C-2-嘧吩基 H 1 716 6-F cf3 C=C-3-遠吩基 H 1 請 717 6_F cf3 C=C-2-噚唑基 H 先 1 閱 1 -i 士 1 718 6-F cf3 C=C-2-嘍唑基 H 背-1 亡 · 719 6-F cf3 C=C_4-異嘮唑基 H 面 之 ^' I 720 6-F cf3 C=C-2-咪唑基 H * - 721 6-F cf3 CH2CH2-cycPr H 爭 1 項I 五 1 722 6-F cf3 CH2CH2CH2CH2OH H % 723 6-F cf3 CH2CH2-CH(OH)Me H 本^ 百 724 6-F cf3 CH2CHr(2-Cl)Ph H Μ 1 1 725 6-F cf3 CH2CH2_(3-Cl)Ph H 1 726 6-F cf3 CH2CH2-(4-Cl)Ph H 1 I 727 6-F cf3 CH2CH2-(2-F)Ph H 1 1 728 6-F cf3 CH2CH2-(3-F)Ph H 訂 729 6-F cf3 CH2CH2-(4-F)Ph H 1 I 730 6-F cf3 CH2CH2_(2-OH)Ph H 1 I 731 6-F cf3 CH2CH2-(3-OH)Ph H 1 1 732 6-F cf3 CH2CH2-(4-〇H)Ph H 1 733 6-F cf3 CH2CH2-(2-OMe)Ph H 1 if 734 6-F cf3 CH2CH2-(3-OMe)Ph H 735 6-F cf3 CH2CH2-(4-OMe)Ph H 1 736 6-F cf3 CH2CHr(2-CN)Ph H Ί 737 6-F cf3 CH2CH2-(3-CN)Ph H 1 738 6-F cf3 CH2CH2_(4_CN)Ph H 1 1 739 6-F cf3 CH2CH2-(2-N02)Ph H 740 6-F cf3 CH2CH2-(3-N02)Ph H 1 I 741 6-F cf3 CH2CH2-(4-N02)Ph H I 742 6-F cf3 CH2CH2-(2-NH2)Ph H 1 1 743 6-F CF3 CH2CH2-(3-NH2)Ph H 1 -84- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 587078 經濟部中央標準局員工消費合作社印製 Μ Β7 82 五、發明説明() 744 6-F cf3 CH2CH2-(4-NH2)Ph H 745 6-F cf3 CH2CH2-(2-NMe2)Ph H 746 6_F cf3 CH2CH2-(3-NMe2)Ph H 747 6-F cf3 CH2CH2-(4-NMe2)Ph H 748 6-F cf3 CH2CH2-3-吡啶基 H 749 6-F cf3 CH2CHr4-吡啶基 H 750 6-F cf3 CH2CH2-2-呋喃基 H 751 6-F cf3 CH2CH2-3-呋喃基 H 752 6-F cf3 CH2CHr2_嘍吩基 H 753 6-F cf3 CH2CHr3-噇吩基 H 754 6-F cf3 CH2CHr2_嘮唑基 H 755 6-F cf3 CH2CHr2_嘍唑基 H 756 6-F cf3 CH2CH2-4-異嘮唑基 H 757 6-F cf3 CH2CH2-2-咪唑基 H 758 6-F cf3 C = C-cycPr ch3 759 6-F cf3 C = C-iPr ch3 760 6-F cf3 C^C-Pr ch3 761 6-F cf3 C^C-Bu ch3 762 6-F cf3 C = C-iBu ch3 763 6-F cf3 C = C-tBu ch3 764 6-F cf3 C^C-Et ch3 765 6-F cf3 C^C-Me ch3 766 6-F cf3 C^C-Ph ch3 767 6_F cf3 〇C-2-吡啶基 ch3 768 6-F cf3 CeC-3-^:咬基 ch3 769 6-F cf3 C Ξ C-4_p比淀基 ch3 770 6-F cf3 C Ξ C_2-咬喃基 ch3 771 6-F cf3 C Ξ C-3-咬喃基 ch3 772 6-F cf3 C = C-2-遠吩基 ch3 773 6-F cf3 C = C-3_^吩基 ch3 -85- (請先閱讀背面之注意Ϋ"項再4-寫本頁)624 5,6-diCl cf3 C = C-2-pyridyl CH2CH3 625 5,6-diCl cf3 CeC-3_p Bicyl CH2CH3 626 5,6-diCl cf3 C Ξ C-4-p Bidyl ch2ch3 627 5 , 6-diCl cf3 C ^ C-2-furyl CH2CH3 628 5,6-diCl cf3 C = C-3-creanyl CH2CH3 629 5,6-diCl cf3 C = C-2-thienyl CH2CH3 630 5, 6-diCl cf3 C ^ C-3-fluorenyl CH2CH3 631 5,6-diCl cf3 C = C-cycPr CH2CH3 632 5,6-diCl cf3 C = C-Ph ch2ch3 633 5,6-diCl cf3 C = C -2-pyridyl ch2ch3 634 5,6-diCl cf3 C = C-3_p than Yodo CH2CH3 635 5,6-diCl cf3 C = C_4_Edianji ch2ch3 636 5,6-diCl cf3 C = C-2_ Furyl ch2ch3 637 5,6-diCl cf3 C = C-3-Branyl ch2ch3 638 5,6-diCl cf3 C = C-2-p Cephenyl CH2CH3 639 5,6-diCl cf3 C = C-3 -p sephenyl ch2ch3 640 5,6-diCl cf3 CH2CH2-cycPr CH2CH3 641 5,6-diCl cf3 CH2CHrPh CH2CH3 642 5,6-diCl cf3 CH2CHr2-pyridyl ch2ch3 643 5,6-diCl cf3 CH2CH2-3-pyridine CH2CH3 644 5,6-diCl cf3 CH2CHr4-pyridyl CH2CH3 645 5,6-diCl cf3 CH2CH2_2_furyl ch2ch3 646 5,6-diCl cf3 CH2CHr3-furyl CH2CH3 647 5,6-diCl cf3 CH2CH2-2-p Cephenyl CH2CH3 648 5,6-diC l cf3 CH2CH2-3-fluorenylCH2CH3 649 6-F cf3 C ^ CCH2CH2OH H 650 6_F cf3 OC-CH (OH) Me H 651 6-F cf3 C ^ C- (2-Cl) Ph H 652 6-F cf3 C = C- (3-Cl) Ph H 653 6-F cf3 C ^ C- (4-Cl) Ph H (Please read the precautions and notes on the back before filling out this page), 1Τ -81-Standard of this paper Applicable to China National Standard (CNS) A4 specification (210X297 mm) 587078 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention (79) 654 6_F cf3 C = C- (2-F) Ph Η 655 6 -F cf3 C ^ C- (3-F) Ph Η 656 6-F cf3 C ^ C- (4-F) Ph Η 657 6-F cf3 C = C- (2_OH) Ph Η 658 6-F cf3 C ^ C- (3-OH) Ph Η 659 6-F cf3 C ^ C- (4-OH) Ph Η 660 6-F cf3 C ^ C- (2-OMe) Ph Η 661 6-F cf3 C «3_OMe ) Ph Η 662 6-F cf3 C = C- (4-OMe) Ph Η 663 6-F cf3 C ^ C- (2-CN) Ph Η 664 6-F cf3 C ^ C- (3-CN) Ph Η 665 6-F cf3 C ^ C- (4-CN) Ph Η 666 6-F cf3 CEC- (2-N02) Ph Η 667 6-F cf3 C ^ C- (3-N02) Ph Η 668 6- F cf3 C ^ C- (4-N02) Ph 669 669 6-F cf3 C tri-C- (2-NH2) Ph Η 670 6-F cf3 C ^ C- (3-NH2) Ph Η 671 6-F cf3 C three C- (4-NH2) Ph Η 672 6-F cf3 C ^ C- (2-NMe2) Ph Η 673 6-F cf3 C ^ C- (3-NMe2 ) Ph Η 674 6-F cf3 C ^ C- (4-NMe2) Ph Η 675 6-F cf3 CeC-3-p ratio Yodo base Η 676 6-F cf3 C three C-4- mouth specific drink: Η 677 6-F cf3 C ^ C-2-creanyl Η 678 6_F cf3 C Ξ C-3-pyranyl Η 679 6-F cf3 C ^ C-2-pyrimyl Η 680 6-F cf3 C Ξ C-3-distenylpyrene 681 6-F cf3 Ce〇2-oxazolylΗ 682 6-F cf3 C = C-2-pyrazolylΗ 683 6-F cf3 C ^ C-4-isohumidazole Base Η -82- (Please read the note r on the back before filling this page) This paper size applies to Chinese National Standard (CNS) A4 (210X297 mm) 587078 A7 B7 V. Description of Invention (8Q) Central Standard of the Ministry of Economic Affairs Printed by the Bureau's Consumer Cooperatives 684 6-F cf3 C = C-2-Mi Junji H 1 1 685 6-F cf3 C = CCH2CH2OH H 1 I 686 6-F cf3 C = C-CH (OH) Me H 1 Please read 1 first, read 1 back, 1 of I, r 1 item 1 fd 687 6-F cf3 C = C- (2-Cl) Ph H 688 6-F cf3 C = C_ (3_Cl) Ph H 689 6 -F cf3 C = C- (4-Cl) Ph H 690 6-F cf3 C = C- (2-F) Ph H 691 6-F cf3 C = C- (3-F) Ph H 692 6-F cf3 C = C- (4-F) Ph H 693 6-F cf3 C = C- (2-OH) Ph H this ^ 694 hundred 6-F cf3 C = C- (3-OH) Ph H month 1 ν ^ I 695 6-F cf3 C = C- (4-OH) Ph H 1 696 6_F cf3 C = C- (2-OMe) Ph H 1 I 697 6-F cf3 C = C- (3-OMe) Ph H 1 I 698 6-F cf3 C = C- (4-OMe) Ph H Order 699 6 -F cf3 C = C- (2-CN) Ph H 1 I 700 6-F cf3 C = C- (3-CN) Ph H 1 I 701 6-F cf3 C = C- (4-CN) Ph H 1 1 702 6-F cf3 C = C- (2-N02) Ph H 1 I 703 6-F cf3 C = C- (3-N02) Ph H 1 704 6-F cf3 C = C- (4-N02 ) Ph H 705 6-F cf3 C = C- (2-NH2) Ph HJ 706 6-F cf3 C = C- (3-NH2) Ph H 707 6-F cf3 OC- (4-NH2) Ph H 1 708 6-F cf3 C = C- (2-NMe2) Ph H 1 1 709 6-F cf3 OC- (3_NMe2) Ph H 710 6-F cf3 C = C- (4-NMe2) Ph H 1 1 711 6 -F cf3 0 = 0-3-0 than Yodo HI 712 6-F cf3 C = C-4-pyridyl H 1 1 713 6-F cf3 C = C-2-pyranyl-83-H 1 1 1 1 1 This paper size applies to Chinese National Standard (CNS) A4 (210X297 mm) 587078 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention (81) 714 6_F cf3 C = C-3-bit Uranyl H 1 715 6-F cf3 C = C-2-pyridinyl H 1 716 6-F cf3 C = C-3-telephenyl H 1 Please 717 6_F cf3 C = C-2-oxazolyl H First read 1 -i person 1 718 6-F cf3 C = C-2-oxazolyl H back-1 death 719 6-F cf3 C = C_4-isooxazolyl H face ^ 'I 720 6 -F cf3 C = C-2-imidazolyl H *-721 6-F cf3 CH2CH2-cycPr H contention 1 item I 5 1 722 6-F cf3 CH2CH2CH2CH2OH H% 723 6-F cf3 CH2CH2-CH (OH) Me H Ben ^ 724 6-F cf3 CH2CHr (2-Cl) Ph H Μ 1 1 725 6-F cf3 CH2CH2_ (3-Cl) Ph H 1 726 6-F cf3 CH2CH2- (4-Cl) Ph H 1 I 727 6-F cf3 CH2CH2- (2-F) Ph H 1 1 728 6-F cf3 CH2CH2- (3-F) Ph H Order 729 6-F cf3 CH2CH2- (4-F) Ph H 1 I 730 6-F cf3 CH2CH2_ (2-OH) Ph H 1 I 731 6-F cf3 CH2CH2- (3-OH) Ph H 1 1 732 6-F cf3 CH2CH2- (4-〇H) Ph H 1 733 6-F cf3 CH2CH2- (2-OMe) Ph H 1 if 734 6-F cf3 CH2CH2- (3-OMe) Ph H 735 6-F cf3 CH2CH2- (4-OMe) Ph H 1 736 6-F cf3 CH2CHr (2-CN) Ph H Ί 737 6-F cf3 CH2CH2- (3-CN) Ph H 1 738 6-F cf3 CH2CH2_ (4_CN) Ph H 1 1 739 6-F cf3 CH2CH2- (2-N02) Ph H 740 6-F cf3 CH2CH2 -(3-N02) Ph H 1 I 741 6-F cf3 CH2CH2- (4-N02) Ph HI 742 6-F cf3 CH2CH2- (2-NH2) Ph H 1 1 743 6-F CF3 CH2CH2- (3- NH2) Ph H 1 -84- This paper size is applicable to Chinese National Standard (CNS) A4 (210X297 mm) 587078 Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs Β7 82 V. Invention Ming () 744 6-F cf3 CH2CH2- (4-NH2) Ph H 745 6-F cf3 CH2CH2- (2-NMe2) Ph H 746 6_F cf3 CH2CH2- (3-NMe2) Ph H 747 6-F cf3 CH2CH2- (4-NMe2) Ph H 748 6-F cf3 CH2CH2-3-pyridyl H 749 6-F cf3 CH2CHr4-pyridyl H 750 6-F cf3 CH2CH2-2-furyl H 751 6-F cf3 CH2CH2-3- Furyl H 752 6-F cf3 CH2CHr2_fluorenyl H 753 6-F cf3 CH2CHr3-fluorenyl H 754 6-F cf3 CH2CHr2_oxazolyl H 755 6-F cf3 CH2CHr2_oxazolyl H 756 6- F cf3 CH2CH2-4-isoxazolyl H 757 6-F cf3 CH2CH2-2-imidazolyl H 758 6-F cf3 C = C-cycPr ch3 759 6-F cf3 C = C-iPr ch3 760 6-F cf3 C ^ C-Pr ch3 761 6-F cf3 C ^ C-Bu ch3 762 6-F cf3 C = C-iBu ch3 763 6-F cf3 C = C-tBu ch3 764 6-F cf3 C ^ C-Et ch3 765 6-F cf3 C ^ C-Me ch3 766 6-F cf3 C ^ C-Ph ch3 767 6_F cf3 〇C-2-pyridyl ch3 768 6-F cf3 CeC-3- ^: bityl ch3 769 6- F cf3 C Ξ C-4_p than Yodo ch3 770 6-F cf3 C Ξ C_2-pyranyl ch3 771 6-F cf3 C Ξ C-3-pyranyl ch3 772 6-F cf3 C = C-2- Far-phenyl ch3 773 6-F cf3 C = C-3_ ^ phenyl ch3 -85- (Please read the note on the back first " 4- Write this page)
、1T 本紙張尺度適用中國國家標準(CNS ) A4規格(210X 297公釐) 587078 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明(83 ) 774 6-F cf3 C=C-cycPr ch3 775 6-F cf3 C=C-iPr ch3 776 6-F cf3 C=C-Pr ch3 777 6-F cf3 OC-Bu ch3 778 6-F cf3 C=C-iBu ch3 779 6-F cf3 C=C-tBu ch3 780 6-F cf3 C=C-Et ch3 781 6-F cf3 C=C_Me ch3 782 6-F cf3 C=C-Ph ch3 783 6-F cf3 C=C-2-吡啶基 ch3 784 6-F cf3 C=C-3-吡啶基 ch3 785 6-F cf3 C=C-4-p比淀基 ch3 786 6-F cf3 C=C-2-呋喃基 ch3 787 6-F cf3 C=C-3-咬喃基 ch3 788 6-F cf3 C=C-2·嘍吩基 ch3 789 6-F cf3 C=C-3-p塞吩基 ch3 790 6-F cf3 CH2CH2-cycPr ch3 791 6-F cf3 CH2CH2-Ph ch3 792 6-F cf3 CH2CHr2-吡啶基 ch3 793 6_F cf3 CH2CH2-3-吡啶基 ch3 794 6-F cf3 CH2CH2-4-吡啶基 ch3 795 6-F cf3 CH2CHr2-呋喃基 ch3 796 6-F cf3 CH2CHr3-呋喃基 ch3 797 6-F cf3 CH2CHr2-嘧吩基 ch3 798 6-F cf3 CH2CH2-3-嚙吩基 ch3 799 6-F cf3 C = C-cycPr ch3 800 6-F cf3 C^C-Ph CH2CH3 801 6-F cf3 CeC_2-吡啶基 CH2CH3 802 6_F cf3 CeC-3-峨淀基 CH2CH3 803 6-F cf3 CeC-4-吡啶基 ch2ch3 -86- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 587078 A7 B7 五、發明説明( 84 經濟部中央標準局員工消費合作社印製、 1T This paper size is applicable to Chinese National Standard (CNS) A4 specification (210X 297 mm) 587078 Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Description of Invention (83) 774 6-F cf3 C = C-cycPr ch3 775 6-F cf3 C = C-iPr ch3 776 6-F cf3 C = C-Pr ch3 777 6-F cf3 OC-Bu ch3 778 6-F cf3 C = C-iBu ch3 779 6-F cf3 C = C-tBu ch3 780 6-F cf3 C = C-Et ch3 781 6-F cf3 C = C_Me ch3 782 6-F cf3 C = C-Ph ch3 783 6-F cf3 C = C-2-pyridyl ch3 784 6-F cf3 C = C-3-pyridyl ch3 785 6-F cf3 C = C-4-p than Yodo ch3 786 6-F cf3 C = C-2-furyl ch3 787 6-F cf3 C = C-3-branyl ch3 788 6-F cf3 C = C-2 · fluorenyl ch3 789 6-F cf3 C = C-3-p sedenyl ch3 790 6-F cf3 CH2CH2-cycPr ch3 791 6 -F cf3 CH2CH2-Ph ch3 792 6-F cf3 CH2CHr2-pyridyl ch3 793 6_F cf3 CH2CH2-3-pyridyl ch3 794 6-F cf3 CH2CH2-4-pyridyl ch3 795 6-F cf3 CH2CHr2-furyl ch3 796 6-F cf3 CH2CHr3-furyl ch3 797 6-F cf3 CH2CHr2-pyrimyl ch3 798 6-F cf3 CH2CH2-3-pyridinyl ch3 799 6-F cf3 C = C-cycPr ch3 800 6-F cf3 C ^ C-Ph CH2CH3 801 6-F cf 3 CeC_2-pyridyl CH2CH3 802 6_F cf3 CeC-3-Edianyl CH2CH3 803 6-F cf3 CeC-4-pyridyl ch2ch3 -86- This paper size applies to China National Standard (CNS) A4 specification (210X297 mm) 587078 A7 B7 V. Description of Invention (84 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs
804 6-F cf3 C = C-2-吱喃基 CH2CH3 805 6-F cf3 C Ξ C-3-咬喃基 ch2ch3 806 6_F cf3 C Ξ C-2-ρ塞吩基 ch2ch3 807 6-F cf3 C e C-3-遠吩基 CH2CH3 808 6-F cf3 C=C-cycPr CH2CH3 809 6-F cf3 C=C_Ph CH2CH3 810 6-F cf3 C=C-2-p比淀基 CH2CH3 811 6-F cf3 C=C-3-p比1基 CH2CH3 812 6-F cf3 C=C-4-#b淀基 CH2CH3 813 6-F cf3 C=C-2-呋喃基 ch2ch3 814 6-F cf3 C=C_3-呋喃基 CH2CH3 815 6-F cf3 C=C_2-嘧吩基 ch2ch3 816 6-F cf3 C=C-3-p塞吩基 CH2CH3 817 6-F cf3 CH2CH2-cycPr CH2CH3 818 6-F cf3 CH2CH2-Ph ch2ch3 819 6-F cf3 CH2CH2-2-吡啶基 CH2CH3 820 6-F cf3 CH2CH2-3-吡啶基 CH2CH3 821 6-F cf3 CH2CHr4-吡啶基 CH2CH3 822 6-F cf3 CH2CH2-2-呋喃基 ch2ch3 823 6-F cf3 CH2CH2-3-呋喃基 CH2CH3 824 6-F cf3 CH2CHr2-嘍吩基 CH2CH3 825 6-F cf3 CH2CH2-3-嘍吩基 ch2ch3 826 5-C1 cf3 C = C-cycPr H 827 5-C1 cf3 C^CCH2CH2OH H 828 5-C1 cf3 C^C-CH(OH)Me H 829 5-C1 cf3 C = C-Ph H 830 5-C1 cf3 C = C-(2-Cl)Ph H 831 5-C1 cf3 C^C-(3-Cl)Ph H 832 5-C1 cf3 C«4_Cl)Ph H 833 5-C1 cf3 C^C-(2-F)Ph H -87· 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 請 先 閱 讀 背 面 Ϊ Ψ 項 再 填· 寫 本 頁 訂 587078 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明(85 )804 6-F cf3 C = C-2-creanyl CH2CH3 805 6-F cf3 C Ξ C-3- sulfanyl ch2ch3 806 6_F cf3 C Ξ C-2-ρ sephenyl ch2ch3 807 6-F cf3 C e C-3-Farphenyl CH2CH3 808 6-F cf3 C = C-cycPr CH2CH3 809 6-F cf3 C = C_Ph CH2CH3 810 6-F cf3 C = C-2-p than Yodo CH2CH3 811 6-F cf3 C = C-3-p ratio 1 group CH2CH3 812 6-F cf3 C = C-4- # bb 基 CH2CH3 813 6-F cf3 C = C-2-furyl ch2ch3 814 6-F cf3 C = C_3- Furyl CH2CH3 815 6-F cf3 C = C_2-pyriminyl ch2ch3 816 6-F cf3 C = C-3-p sedenyl CH2CH3 817 6-F cf3 CH2CH2-cycPr CH2CH3 818 6-F cf3 CH2CH2-Ph ch2ch3 819 6-F cf3 CH2CH2-2-pyridyl CH2CH3 820 6-F cf3 CH2CH2-3-pyridyl CH2CH3 821 6-F cf3 CH2CHr4-pyridyl CH2CH3 822 6-F cf3 CH2CH2-2-furyl ch2ch3 823 6-F cf3 CH2CH2-3-furylCH2CH3 824 6-F cf3 CH2CHr2-fluorenyl CH2CH3 825 6-F cf3 CH2CH2-3-fluorenyl ch2ch3 826 5-C1 cf3 C = C-cycPr H 827 5-C1 cf3 C ^ CCH2CH2OH H 828 5-C1 cf3 C ^ C-CH (OH) Me H 829 5-C1 cf3 C = C-Ph H 830 5-C1 cf3 C = C- (2-Cl) Ph H 831 5-C1 cf3 C ^ C- (3-Cl) Ph H 832 5-C1 cf3 C «4_Cl) Ph H 833 5-C1 cf3 C ^ C- (2-F) Ph H -87 · This paper size is applicable to Chinese National Standard (CNS) A4 (210X297 mm) Please read the Ϊ item on the back side and fill in the page. · Write this page to order 587078 Printed by the Consumer Standards Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs A7 B7 V. Invention Description
834 5-C1 cf3 C = C-(3-F)Ph H 835 5-C1 cf3 C^C-(4-F)Ph H 836 5-C1 cf3 C^C-(2-OH)Ph H 837 5-C1 cf3 C^C-(3-OH)Ph H 838 5-C1 cf3 C^C-(4-OH)Ph H 839 5-C1 cf3 C^C-(2-OMe)Ph H 840 5-C1 cf3 C^C-(3-0Me)Ph H 841 5-C1 cf3 C«4-OMe)Ph H 842 5-C1 cf3 C^C-(2-CN)Ph H 843 5-C1 cf3 C^C-(3-CN)Ph H 844 5-C1 cf3 C^C-(4-CN)Ph H 845 5-C1 cf3 C^C-(2-N02)Ph H 846 5-C1 cf3 CEC-(3_N02)Ph H 847 5-C1 cf3 CEC-(4_N02)Ph H 848 5-C1 cf3 C^C-(2-NH2)Ph H 849 5-C1 cf3 C^C-(3-NH2)Ph H 850 5-C1 cf3 C^C-(4-NH2)Ph H 851 5-C1 cf3 C^C-(2-NMe2)Ph H 852 5-C1 cf3 C = C-(3-NMe2)Ph H 853 5-C1 cf3 C^C-(4-NMe2)Ph H 854 5-C1 cf3 CeC-2-吡啶基 H 855 5-C1 cf3 C Ξ C-2-p比淀基 H 856 5-C1 cf3 C Ξ C-3-峨淀基 H 857 5-C1 cf3 C e C-4-p比淀基 H 858 5-C1 cf3 C Ξ C-2-咬喃基 H 859 5-C1 cf3 C Ξ C-3-咬喃基 H 860 5-C1 cf3 〇C-2-嘍吩基 H 861 5-C1 cf3 C ξ C-3-遠吩基 H 862 5-C1 cf3 〇C-2_崎唑基 H 863 5-C1 cf3 C^C-2_嘧哇基 H -88- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X 297公釐) 587078 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明(86 )834 5-C1 cf3 C = C- (3-F) Ph H 835 5-C1 cf3 C ^ C- (4-F) Ph H 836 5-C1 cf3 C ^ C- (2-OH) Ph H 837 5 -C1 cf3 C ^ C- (3-OH) Ph H 838 5-C1 cf3 C ^ C- (4-OH) Ph H 839 5-C1 cf3 C ^ C- (2-OMe) Ph H 840 5-C1 cf3 C ^ C- (3-0Me) Ph H 841 5-C1 cf3 C «4-OMe) Ph H 842 5-C1 cf3 C ^ C- (2-CN) Ph H 843 5-C1 cf3 C ^ C- (3-CN) Ph H 844 5-C1 cf3 C ^ C- (4-CN) Ph H 845 5-C1 cf3 C ^ C- (2-N02) Ph H 846 5-C1 cf3 CEC- (3_N02) Ph H 847 5-C1 cf3 CEC- (4_N02) Ph H 848 5-C1 cf3 C ^ C- (2-NH2) Ph H 849 5-C1 cf3 C ^ C- (3-NH2) Ph H 850 5-C1 cf3 C ^ C- (4-NH2) Ph H 851 5-C1 cf3 C ^ C- (2-NMe2) Ph H 852 5-C1 cf3 C = C- (3-NMe2) Ph H 853 5-C1 cf3 C ^ C- (4-NMe2) Ph H 854 5-C1 cf3 CeC-2-pyridyl H 855 5-C1 cf3 C Ξ C-2-p than Yodoyl H 856 5-C1 cf3 C Ξ C-3-Edian H 857 5-C1 cf3 C e C-4-p than Yodo H 858 5-C1 cf3 C Ξ C-2-pyranyl H 859 5-C1 cf3 C Ξ C-3-pyranyl H 860 5 -C1 cf3 〇C-2-fluorenyl H 861 5-C1 cf3 C ξ C-3-distenyl H 862 5-C1 cf3 〇C-2_azazolyl H 863 5-C1 cf3 C ^ C- 2_ pyrimidyl H -88- This paper size applies to China National Standard (CNS) A4 specifications (2 10X 297 mm) 587078 Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs A7 B7 V. Description of Invention (86)
864 5-C1 cf3 C = C-4-異嘮唑基 H 865 5-C1 cf3 C = C-2-咪唑基 H 866 5-C1 cf3 C=C-cycPr H 867 5-C1 cf3 C=CCH2CH2OH H 868 5-C1 cf3 C=C-CH(OH)Me H 869 5-C1 cf3 C=C-Ph H 870 5-C1 cf3 C=C-(2-Cl)Ph H 871 5-C1 cf3 C=C-(3-Cl)Ph H 872 5-C1 cf3 C=C_(4-Cl)Ph H 873 5-C1 cf3 C=C-(2-F)Ph H 874 5-C1 cf3 C=C-(3-F)Ph H 875 5-C1 cf3 C=C-(4-F)Ph H 876 5-C1 cf3 C=C-(2-OH)Ph H 877 5-C1 cf3 C=C-(3-OH)Ph H 878 5-C1 cf3 C=C-(4-OH)Ph H 879 5-C1 cf3 C=C-(2-OMe)Ph H 880 5-C1 cf3 C=C-(3-OMe)Ph H 881 5-C1 cf3 C=C-(4-OMe)Ph H 882 5-C1 cf3 C=C-(2-CN)Ph H 883 5-C1 cf3 C=C-(3-CN)Ph H 884 5-C1 cf3 C=C-(4-CN)Ph H 885 5-C1 cf3 C=C_(2-N02)Ph H 886 5-C1 cf3 C=C-(3-N02)Ph H 887 5-C1 cf3 C=C-(4-N02)Ph H 888 5-C1 cf3 C=C-(2-NH2)Ph H 889 5-C1 cf3 C=C-(3-NH2)Ph H 890 5-C1 cf3 C=C-(4-NH2)Ph H 891 5-C1 cf3 C=C-(2-NMe2)Ph H 892 5-C1 cf3 C=C-(3-NMe2)Ph H 893 5-C1 cf3 C=C-(4-NMe2)Ph H (請先閲讀背面之注意事項再填寫本頁) d 訂 -89 - 本紙張尺度適用中國國家標準(CNS ) A4規格(210X 297公釐) 587078 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明(87 )864 5-C1 cf3 C = C-4-isoxazolyl H 865 5-C1 cf3 C = C-2-imidazolyl H 866 5-C1 cf3 C = C-cycPr H 867 5-C1 cf3 C = CCH2CH2OH H 868 5-C1 cf3 C = C-CH (OH) Me H 869 5-C1 cf3 C = C-Ph H 870 5-C1 cf3 C = C- (2-Cl) Ph H 871 5-C1 cf3 C = C -(3-Cl) Ph H 872 5-C1 cf3 C = C_ (4-Cl) Ph H 873 5-C1 cf3 C = C- (2-F) Ph H 874 5-C1 cf3 C = C- (3 -F) Ph H 875 5-C1 cf3 C = C- (4-F) Ph H 876 5-C1 cf3 C = C- (2-OH) Ph H 877 5-C1 cf3 C = C- (3-OH ) Ph H 878 5-C1 cf3 C = C- (4-OH) Ph H 879 5-C1 cf3 C = C- (2-OMe) Ph H 880 5-C1 cf3 C = C- (3-OMe) Ph H 881 5-C1 cf3 C = C- (4-OMe) Ph H 882 5-C1 cf3 C = C- (2-CN) Ph H 883 5-C1 cf3 C = C- (3-CN) Ph H 884 5-C1 cf3 C = C- (4-CN) Ph H 885 5-C1 cf3 C = C_ (2-N02) Ph H 886 5-C1 cf3 C = C- (3-N02) Ph H 887 5-C1 cf3 C = C- (4-N02) Ph H 888 5-C1 cf3 C = C- (2-NH2) Ph H 889 5-C1 cf3 C = C- (3-NH2) Ph H 890 5-C1 cf3 C = C- (4-NH2) Ph H 891 5-C1 cf3 C = C- (2-NMe2) Ph H 892 5-C1 cf3 C = C- (3-NMe2) Ph H 893 5-C1 cf3 C = C -(4-NMe2) Ph H (Please read the notes on the back before filling in this page) d Order-89-This paper size applies to China National Standard (CNS) A4 regulations Grid (210X 297 mm) 587078 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Invention Description (87)
894 5-C1 cf3 C=C-2-p 比 基 H 895 5-C1 cf3 C=C-2-吡啶基 H 896 5-C1 cf3 C=C-3-吡啶基 H 897 5-C1 cf3 C=C-4-p比淀基 H 898 5-C1 cf3 C=C_2-呋喃基 H 899 5-C1 cf3 C=C-3-咬喃基 H 900 5-C1 cf3 OC-2-嘍吩基 H 901 5-C1 cf3 C=C-3-嘍吩基 H 902 5-C1 cf3 C=C-2-呤唑基 H 903 5-C1 cf3 C=C-2-^ 唑基 H 904 5-C1 cf3 〇C-4-異嘮唑基 H 905 5-C1 cf3 C=C-2-咪唑基 H 906 5-C1 cf3 CH2CH2-cycPr H 907 5-C1 cf3 CH2CH2CH2CH2OH H 908 5-C1 cf3 CH2CH2-CH(OH)Me H 909 5-C1 cf3 CH2CH2-Ph H 910 5-C1 cf3 CH2CHr(2-Cl)Ph H 911 5-C1 cf3 CH2CH2-(3-Cl)Ph H 912 5-C1 cf3 CH2CH2-(4-Cl)Ph H 913 5-C1 cf3 CH2CH2-(2-F)Ph H 914 5-C1 cf3 CH2CH2-(3-F)Ph H 915 5-C1 cf3 CH2CH2-(4-F)Ph H 916 5-C1 cf3 CH2CH2-(2-OH)Ph H 917 5-C1 cf3 CH2CHr(3-OH)Ph H 918 5-C1 cf3 CH2CH2-(4-OH)Ph H 919 5-C1 cf3 CH2CHr(2-OMe)Ph H 920 5-C1 cf3 CH2CH2-(3-OMe)Ph H 921 5-C1 cf3 CH2CH2-(4-OMe)Ph H 922 5-C1 cf3 CH2CHr(2-CN)Ph H 923 5-C1 cf3 CH2CHr(3-CN)Ph H -90 - (請先閱讀背面之注意事項再填寫本頁) 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 587078 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明(88 ) 924 5-C1 cf3 CH2CH2-(4-CN)Ph Η 925 5-C1 cf3 CH2CH2-(2-N02)Ph Η 926 5-C1 cf3 CH2CH2-(3-N02)Ph Η 927 5-C1 cf3 CH2CH2-(4-N02)Ph Η 928 5-C1 cf3 CH2CH2-(2-NH2)Ph Η 929 5-C1 cf3 CH2CHr(3-NH2)Ph Η 930 5-C1 cf3 CH2CH2-(4-NH2)Ph Η 931 5-C1 cf3 CH2CH2-(2-NMe2)Ph Η 932 5-C1 cf3 CH2CH2-(3-NMe2)Ph Η 933 5-C1 CFs CH2CH2-(4-NMe2)Ph Η 934 5-C1 cf3 CH2CH2-2-吡啶基 Η 935 5-C1 cf3 CH2CH2-3·吡啶基 Η 936 5-C1 cf3 CH2CH2-4-吡啶基 Η 937 5-C1 cf3 CH2CHr2-呋喃基 Η 938 5-C1 cf3 CH2CH2-3_呋喃基 Η 939 5-C1 cf3 CH2CHr2·嘧吩基 Η 940 5-C1 cf3 CH2CH2-3-嘧吩基 Η 941 5-C1 cf3 CH2CH2-2-嘮唑基 Η 942 5-C1 cf3 CH2CH2-2-嘍唑基 Η 943 5·α cf3 CH2CH2-4-異嘮唑基 Η 944 5-Cl cf3 CH2CH2-2-咪唑基 Η 945 5-C1 cf3 C = C-cycPr ch3 946 5·α cf3 C^C-Ph ch3 947 5-C1 cf3 C = C-2-p比咬基 ch3 948 5-α cf3 Ce〇3-吡啶基 ch3 949 5-C1 cf3 C Ξ C_4-口比淀基 ch3 950 5-C1 cf3 C Ξ C_2·咬喃基 ch3 951 5-α cf3 C = C-3-咬喃基 ch3 952 5·α CFs C = C-2-遠吩基 ch3 953 5-C1 cf3 C Ξ C-3-ρ塞吩基 ch3 (請先閱讀背面之注意事項再填寫本頁) -91 - 本紙張尺度適用中國國家標準(CNS ) A4規格(210X 297公釐) 587078 經濟部中央標準局員工消費合作社印製 Μ Β7 五、發明説明(89 ) 954 5-C1 cf3 C=C-cycPr ch3 955 5-C1 cf3 C=C-Ph ch3 956 5-C1 cf3 ¢=02-0比淀基 ch3 957 5-C1 cf3 C=C-3-吡啶基 ch3 958 5-C1 cf3 C=C-4-吡啶基 ch3 959 5-C1 cf3 C=C-2-咬喃基 ch3 960 5-C1 cf3 C=C-3-呋喃基 ch3 961 5-C1 cf3 C=C-2-嘍吩基 ch3 962 5-C1 cf3 C=C-3-p塞吩基 ch3 963 5-C1 cf3 CH2CH2-cycPr ch3 964 5-C1 cf3 CH2CH2-Ph ch3 965 5-C1 cf3 CH2CHr2-吡啶基 ch3 966 5-C1 cf3 CH2CHr3-吡啶基 ch3 967 5-C1 cf3 CH2CHr4·吡啶基 ch3 968 5-C1 cf3 CH2CH2-2-呋喃基 ch3 969 5-C1 cf3 CH2CH2-3-呋喃基 ch3 970 5-C1 cf3 CH2CH2-2-嘍吩基 ch3 971 5-C1 cf3 CH2CHr3-嘧吩基 ch3 972 5-C1 cf3 C = C-cycPr ch2ch3 973 5-C1 cf3 C^C-Ph ch2ch3 974 5-C1 cf3 CeC-2-吡啶基 CH2CH3 975 5·α cf3 CeC-3-p比淀基 ch2ch3 976 5-C1 cf3 CeC-4-吡啶基 CH2CH3 977 5-C1 cf3 C = C-2-呋喃基 CH2CH3 978 5-C1 cf3 C Ξ C-3-咬喃基 ch2ch3 979 5-C1 cf3 C Ξ C-2-p塞吩基 ch2ch3 980 5-C1 cf3 C = C-3-嘍吩基 ch2ch3 981 5-C1 cf3 C=C-cycPr CH2CH3 982 5-C1 cf3 C=C-Ph ch2ch3 983 5-C1 cf3 C=C-2-吡啶基 CH2CH3 (請先閱讀背面之注意W項再4-寫本頁) -92 - 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 587078 經濟部中央標準局員工消費合作社印製 A7 B7 - 五、發明説明() 984 5-C1 cf3 OC-3-吡啶基 CH2CH3 1 1 985 5-C1 cf3 OC-4-吡啶基 CH2CH3 1 986 5-C1 cf3 C=C-2-呋喃基 CH2CH3 1 請 987 5-C1 cf3 C=C_3_呋喃基 CH2CH3 龙1 閱 988 5-C1 cf3 C=C-2-嘧吩基 CH2CH3 讀 背1 989 5-C1 cf3 C=C-3·嘧吩基 CH2CH3 面 | 之 '' I 990 5-C1 cf3 CH2CH2-cycPr CH2CH3 t - 991 5-C1 cf3 CH2CH2-Ph ch2ch3 爭 1 項 I 992 5-C1 cf3 CH2CHr2-吡啶基 CH2CH3 再 1 填,j 993 5-C1 cf3 CH2CH2-3-吡啶基 CH2CH3 本7 994 5-C1 cf3 CH2CHr4-吡啶基 CH2CH3 頁 1 995 5-C1 cf3 CH2CH2-2-呋喃基 CH2CH3 1 996 5-C1 cf3 CH2CH2-3-呋喃基 CH2CH3 1 1 997 5-C1 cf3 CH2CHr2-噹吩基 CH2CH3 1 I 998 5-C1 cf3 CH2CHr3-嘍吩基 CH2CH3 1 訂 999 5-F cf3 C = C-cycPr H 1 I 1000 5-F cf3 C = CCH2CH2OH H 1 I 1001 5-F cf3 C^C-CH(OH)Me H 1 I 1002 5-F cf3 C = C-Ph H 1 1003 5-F cf3 C = C-(2-Cl)Ph H 1 1004 5-F cf3 C^C-(3-Cl)Ph H # 1005 5-F cf3 C^C-(4-Cl)Ph H 1 1 1006 5-F cf3 C^C-(2-F)Ph H Ί 1007 5-F cf3 C^C-(3-F)Ph H 1 1008 5-F cf3 C^C-(4-F)Ph H 1 I 1009 5-F cf3 C«2_OH)Ph H _ 1 1010 5-F cf3 〇C_(3_OH)Ph H 1 I 1011 5-F cf3 C^C-(4-OH)Ph H I 1012 5-F cf3 C^C-(2-OMe)Ph H 1 1 1013 5-F cf3 C^C-(3-OMe)Ph H 1 -93 - 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 587078 Μ Β7 五、發明説明( 91 經濟部中央標準局員工消費合作社印製894 5-C1 cf3 C = C-2-p specific group H 895 5-C1 cf3 C = C-2-pyridyl H 896 5-C1 cf3 C = C-3-pyridyl H 897 5-C1 cf3 C = C-4-p than Yodo H 898 5-C1 cf3 C = C_2-furyl H 899 5-C1 cf3 C = C-3-pyranyl H 900 5-C1 cf3 OC-2-fluorenyl H 901 5-C1 cf3 C = C-3-fluorenyl H 902 5-C1 cf3 C = C-2-pyrazolyl H 903 5-C1 cf3 C = C-2- ^ oxazolyl H 904 5-C1 cf3. C-4-Isoxazolyl H 905 5-C1 cf3 C = C-2-imidazolyl H 906 5-C1 cf3 CH2CH2-cycPr H 907 5-C1 cf3 CH2CH2CH2CH2OH H 908 5-C1 cf3 CH2CH2-CH (OH) Me H 909 5-C1 cf3 CH2CH2-Ph H 910 5-C1 cf3 CH2CHr (2-Cl) Ph H 911 5-C1 cf3 CH2CH2- (3-Cl) Ph H 912 5-C1 cf3 CH2CH2- (4-Cl) Ph H 913 5-C1 cf3 CH2CH2- (2-F) Ph H 914 5-C1 cf3 CH2CH2- (3-F) Ph H 915 5-C1 cf3 CH2CH2- (4-F) Ph H 916 5-C1 cf3 CH2CH2 -(2-OH) Ph H 917 5-C1 cf3 CH2CHr (3-OH) Ph H 918 5-C1 cf3 CH2CH2- (4-OH) Ph H 919 5-C1 cf3 CH2CHr (2-OMe) Ph H 920 5 -C1 cf3 CH2CH2- (3-OMe) Ph H 921 5-C1 cf3 CH2CH2- (4-OMe) Ph H 922 5-C1 cf3 CH2CHr (2-CN) Ph H 923 5-C1 cf3 CH2CHr (3-CN) Ph H -90-(Please read the notes on the back before filling in this ) This paper size applies to Chinese National Standard (CNS) A4 specification (210X297 mm) 587078 Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs A7 B7 5. Invention Description (88) 924 5-C1 cf3 CH2CH2- (4-CN) Ph Η 925 5-C1 cf3 CH2CH2- (2-N02) Ph Η 926 5-C1 cf3 CH2CH2- (3-N02) Ph Η 927 5-C1 cf3 CH2CH2- (4-N02) Ph Η 928 5-C1 cf3 CH2CH2 -(2-NH2) Ph Η 929 5-C1 cf3 CH2CHr (3-NH2) Ph 930 930 5-C1 cf3 CH2CH2- (4-NH2) Ph Η 931 5-C1 cf3 CH2CH2- (2-NMe2) Ph Η 932 5-C1 cf3 CH2CH2- (3-NMe2) Ph Η 933 5-C1 CFs CH2CH2- (4-NMe2) Ph Η 934 5-C1 cf3 CH2CH2-2-pyridylΗ 935 5-C1 cf3 CH2CH2-3 · pyridyl Η 936 5-C1 cf3 CH2CH2-4-pyridylΗ 937 5-C1 cf3 CH2CHr2-furylΗ 938 5-C1 cf3 CH2CH2-3_furanylΗ 939 5-C1 cf3 CH2CHr2 · pyrimylΗ 940 5-C1 cf3 CH2CH2-3-pyrimidinyl Η 941 5-C1 cf3 CH2CH2-2-oxazolyl Η 942 5-C1 cf3 CH2CH2-2-oxazolyl Η 943 5.α cf3 CH2CH2-4-isooxazolyl Η 944 5-Cl cf3 CH2CH2-2-imidazolylΗ 945 5-C1 cf3 C = C-cycPr ch3 946 5.α cf3 C ^ C-Ph ch3 947 5-C1 cf3 C = C-2-p ch3 948 5-α cf3 Ce〇3-pyridyl ch3 949 5-C1 cf3 C Ξ C_4-O-pyridyl ch3 950 5-C1 cf3 C Ξ C_2 · Branyl ch3 951 5-α cf3 C = C-3 -Chrysanyl ch3 952 5 · α CFs C = C-2-distenyl ch3 953 5-C1 cf3 C Ξ C-3-ρ sephenyl ch3 (Please read the precautions on the back before filling this page)- 91-This paper size applies to Chinese National Standard (CNS) A4 (210X 297 mm) 587078 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs Β7 V. Description of the Invention (89) 954 5-C1 cf3 C = C-cycPr ch3 955 5-C1 cf3 C = C-Ph ch3 956 5-C1 cf3 ¢ = 02-0 than Yodo ch3 957 5-C1 cf3 C = C-3-pyridyl ch3 958 5-C1 cf3 C = C-4 -Pyridyl ch3 959 5-C1 cf3 C = C-2-octyl ch3 960 5-C1 cf3 C = C-3-furyl ch3 961 5-C1 cf3 C = C-2-fluorenyl ch3 962 5 -C1 cf3 C = C-3-p sephenyl ch3 963 5-C1 cf3 CH2CH2-cycPr ch3 964 5-C1 cf3 CH2CH2-Ph ch3 965 5-C1 cf3 CH2CHr2-pyridyl ch3 966 5-C1 cf3 CH2CHr3-pyridine Ch3 967 5-C1 cf3 CH2CHr4pyridyl ch3 968 5-C1 cf3 CH2CH2-2-furyl ch3 969 5-C1 cf3 CH2CH2-3-furyl ch3 970 5-C1 c f3 CH2CH2-2-fluorenyl ch3 971 5-C1 cf3 CH2CHr3-pyriminyl ch3 972 5-C1 cf3 C = C-cycPr ch2ch3 973 5-C1 cf3 C ^ C-Ph ch2ch3 974 5-C1 cf3 CeC-2 -Pyridyl CH2CH3 975 5.α cf3 CeC-3-p than ytyl ch2ch3 976 5-C1 cf3 CeC-4-pyridyl CH2CH3 977 5-C1 cf3 C = C-2-furyl CH2CH3 978 5-C1 cf3 C Ξ C-3-pyranyl ch2ch3 979 5-C1 cf3 C Ξ C-2-p sedenyl ch2ch3 980 5-C1 cf3 C = C-3-fluorenyl ch2ch3 981 5-C1 cf3 C = C-cycPr CH2CH3 982 5-C1 cf3 C = C-Ph ch2ch3 983 5-C1 cf3 C = C-2-pyridyl CH2CH3 (Please read the note on the back first and then 4-write this page) -92-This paper size applies to China National Standard (CNS) A4 specification (210X297 mm) 587078 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economy A7 B7-V. Description of the invention () 984 5-C1 cf3 OC-3-pyridyl CH2CH3 1 1 985 5-C1 cf3 OC-4-pyridyl CH2CH3 1 986 5-C1 cf3 C = C-2-furanyl CH2CH3 1 Please 987 5-C1 cf3 C = C_3_furanyl CH2CH3 Dragon 1 See 988 5-C1 cf3 C = C-2 -Pyridinyl CH2CH3 Read back 1 989 5-C1 cf3 C = C-3 · Pyridinyl CH2CH3 face | of I 990 5-C1 cf3 CH2CH2-c ycPr CH2CH3 t-991 5-C1 cf3 CH2CH2-Ph ch2ch3 Compete for one item I 992 5-C1 cf3 CH2CHr2-pyridyl CH2CH3 One more, j 993 5-C1 cf3 CH2CH2-3-pyridyl CH2CH3 Ben 7 994 5-C1 cf3 CH2CHr4-pyridylCH2CH3 Page 1 995 5-C1 cf3 CH2CH2-2-furyl CH2CH3 1 996 5-C1 cf3 CH2CH2-3-furanyl CH2CH3 1 1 997 5-C1 cf3 CH2CHr2-Angyl CH2CH3 1 I 998 5 -C1 cf3 CH2CHr3-fluorenylCH2CH3 1 Order 999 5-F cf3 C = C-cycPr H 1 I 1000 5-F cf3 C = CCH2CH2OH H 1 I 1001 5-F cf3 C ^ C-CH (OH) Me H 1 I 1002 5-F cf3 C = C-Ph H 1 1003 5-F cf3 C = C- (2-Cl) Ph H 1 1004 5-F cf3 C ^ C- (3-Cl) Ph H # 1005 5 -F cf3 C ^ C- (4-Cl) Ph H 1 1 1006 5-F cf3 C ^ C- (2-F) Ph H Ί 1007 5-F cf3 C ^ C- (3-F) Ph H 1 1008 5-F cf3 C ^ C- (4-F) Ph H 1 I 1009 5-F cf3 C «2_OH) Ph H _ 1 1010 5-F cf3 〇C_ (3_OH) Ph H 1 I 1011 5-F cf3 C ^ C- (4-OH) Ph HI 1012 5-F cf3 C ^ C- (2-OMe) Ph H 1 1 1013 5-F cf3 C ^ C- (3-OMe) Ph H 1 -93-book Paper size applies Chinese National Standard (CNS) A4 (210X297 mm) 587078 Μ B7 V. Description of invention (91 Central Bureau of Standards, Ministry of Economic Affairs Workers Co-op print
1014 5-F cf3 C = C-(4-OMe)Ph H 1015 5-F cf3 C = C-(2-CN)Ph H 1016 5-F cf3 C^C-(3-CN)Ph H 1017 5-F cf3 C^C-(4-CN)Ph H 1018 5-F cf3 C 三 C-(2_N02)Ph H 1019 5-F cf3 C 三 C_(3-N02)Ph H 1020 5_F cf3 C = C-(4-N02)Ph H 1021 5-F cf3 C^C-(2-NH2)Ph H 1022 5-F cf3 C^C-(3-NH2)Ph H 1023 5-F cf3 C^C-(4-NH2)Ph H 1024 5-F cf3 C^C-(2-NMe2)Ph H 1025 5-F cf3 C = C-(3-NMe2)Ph H 1026 5-F cf3 C^C-(4-NMe2)Ph H 1027 5-F cf3 C Ξ C_2-口比淀基 H 1028 5-F cf3 C Ξ C-2-p比淀基 H 1029 5-F cf3 CeC-3-p比淀基 H 1030 5-F cf3 C = H 1031 5-F cf3 C Ξ C-2-咬喃基 H 1032 5-F cf3 〇C_3-呋喃基 H 1033 5-F cf3 〇C-2-嘍吩基 H 1034 5-F cf3 C Ξ C-3-p塞吩基 H 1035 5-F cf3 〇 02-嘮唑基 H 1036 5-F cf3 OC-2-嘧唑基 H 1037 5-F cf3 C = C-4-異嘮唑基 H 1038 5-F cf3 C^C-2-咪唑基 H 1039 5-F cf3 C=C-cycPr H 1040 5-F cf3 C=CCH2CH2OH H 1041 5-F cf3 C=C-CH(0H)Me H 1042 5-F cf3 C=C-Ph H 1043 5-F cf3 C=C-(2-Cl)Ph H -94- 本紙張尺度適用中國國家標準(CNS ) Α4規格(210 Χ 297公釐) 請 閱 讀 背 ιέ 意 事· 項 再 填_ 寫 本 頁 訂 587078 經濟部中央標準局員工消費合作社印製 kl B7 92 五、發明説明() 1044 5-F cf3 C=C-(3-Cl)Ph Η 1045 5-F cf3 C=C-(4-Cl)Ph Η 1046 5-F cf3 C=C-(2-F)Ph Η 1047 5-F cf3 C=C-(3-F)Ph Η 1048 5-F cf3 C=C_(4_F)Ph Η 1049 5-F cf3 C=C-(2-OH)Ph Η 1050 5-F cf3 〇C-(3_OH)Ph Η 1051 5-F cf3 C=C-(4_OH)Ph Η 1052 5-F cf3 C=C-(2_OMe)Ph Η 1053 5-F cf3 C=C-(3-OMe)Ph Η 1054 5-F cf3 OC-(4-OMe)Ph Η 1055 5-F cf3 C=C-(2-CN)Ph Η 1056 5-F cf3 C=C-(3_CN)Ph Η 1057 5-F cf3 C=C_(4-CN)Ph Η 1058 5-F cf3 C=C-(2-N02)Ph Η 1059 5-F cf3 C=C-(3-N02)Ph Η 1060 5-F cf3 C=C-(4-N02)Ph Η 1061 5-F cf3 C=C-(2-NH:>)Ph Η 1062 5-F cf3 C=C-(3-NH2)Ph Η 1063 5-F cf3 C=C-(4-NH2)Ph Η 1064 5-F CFb C=C-(2-NMe2)Ph Η 1065 5-F cf3 C=C-(3-NMe2)Ph Η 1066 5-F cf3 C=C-(4-NMe2)Ph Η 1067 5-F cf3 C=C-2-吡啶基 Η 1068 5-F cf3 C=C-2-p比淀基 Η 1069 5-F cf3 C=C_3-吡啶基 Η 1070 5-F cf3 C=C_4_吡啶基 Η 1071 5-F cf3 C=C-2-呋喃基 Η 1072 5_F cf3 C=C-3-咬喃基 Η 1073 5-F cf3 C=C-2-p塞吩基 Η -95- (請先閱讀背面之注意事項再填寫本頁) "口 本紙張尺度適用中國國家標準(CNS ) A4規格(210X 297公釐) 587078 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明(93 )1014 5-F cf3 C = C- (4-OMe) Ph H 1015 5-F cf3 C = C- (2-CN) Ph H 1016 5-F cf3 C ^ C- (3-CN) Ph H 1017 5 -F cf3 C ^ C- (4-CN) Ph H 1018 5-F cf3 C three C- (2_N02) Ph H 1019 5-F cf3 C three C_ (3-N02) Ph H 1020 5_F cf3 C = C- (4-N02) Ph H 1021 5-F cf3 C ^ C- (2-NH2) Ph H 1022 5-F cf3 C ^ C- (3-NH2) Ph H 1023 5-F cf3 C ^ C- (4 -NH2) Ph H 1024 5-F cf3 C ^ C- (2-NMe2) Ph H 1025 5-F cf3 C = C- (3-NMe2) Ph H 1026 5-F cf3 C ^ C- (4-NMe2 ) Ph H 1027 5-F cf3 C Ξ C_2-Hydro-based H 1028 5-F cf3 C Ξ C-2-p Hydro-based H 1029 5-F cf3 CeC-3-p Hydro-based H 1030 5- F cf3 C = H 1031 5-F cf3 C Ξ C-2-octanoyl H 1032 5-F cf3 〇C_3-furyl H 1033 5-F cf3 〇C-2-fluorenyl H 1034 5-F cf3 C Ξ C-3-p sephenyl H 1035 5-F cf3 〇02-oxazolyl H 1036 5-F cf3 OC-2-pyrazolyl H 1037 5-F cf3 C = C-4-isoxazole H 1038 5-F cf3 C ^ C-2-imidazolyl H 1039 5-F cf3 C = C-cycPr H 1040 5-F cf3 C = CCH2CH2OH H 1041 5-F cf3 C = C-CH (0H) Me H 1042 5-F cf3 C = C-Ph H 1043 5-F cf3 C = C- (2-Cl) Ph H -94- This paper size applies to China National Standard (CNS) Α4 specifications 210 χ 297 mm) Please read the intent and refill the item _ write this page to order 587078 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs kl B7 92 V. Description of the invention () 1044 5-F cf3 C = C- (3-Cl) Ph Η 1045 5-F cf3 C = C- (4-Cl) Ph Η 1046 5-F cf3 C = C- (2-F) Ph Η 1047 5-F cf3 C = C- (3 -F) Ph Η 1048 5-F cf3 C = C_ (4_F) Ph Η 1049 5-F cf3 C = C- (2-OH) Ph Η 1050 5-F cf3 〇C- (3_OH) Ph Η 1051 5- F cf3 C = C- (4_OH) Ph Η 1052 5-F cf3 C = C- (2_OMe) Ph Η 1053 5-F cf3 C = C- (3-OMe) Ph Η 1054 5-F cf3 OC- (4 -OMe) Ph Η 1055 5-F cf3 C = C- (2-CN) Ph Η 1056 5-F cf3 C = C- (3_CN) Ph Η 1057 5-F cf3 C = C_ (4-CN) Ph Η 1058 5-F cf3 C = C- (2-N02) Ph Η 1059 5-F cf3 C = C- (3-N02) Ph Η 1060 5-F cf3 C = C- (4-N02) Ph Η 1061 5 -F cf3 C = C- (2-NH: >) Ph Η 1062 5-F cf3 C = C- (3-NH2) Ph Η 1063 5-F cf3 C = C- (4-NH2) Ph Η 1064 5-F CFb C = C- (2-NMe2) Ph Η 1065 5-F cf3 C = C- (3-NMe2) Ph Η 1066 5-F cf3 C = C- (4-NMe2) Ph Η 1067 5- F cf3 C = C-2-pyridylΗ 1068 5-F cf3 C = C-2-p ratio ytyl 淀 1069 5-F cf3 C = C_3-pyridylΗ 1070 5-F cf3 C = C_ 4-pyridinyl fluorene 1071 5-F cf3 C = C-2-furyl fluorene 1072 5_F cf3 C = C-3-pyranyl fluorene 1073 5-F cf3 C = C-2-p cephenyl fluorene -95 -(Please read the notes on the back before filling out this page) " The size of the paper is applicable to the Chinese National Standard (CNS) A4 (210X 297 mm) 587078 Printed by the Consumer Standards Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 5. Description of the invention (93)
1074 5_F cf3 C=C-3-嘧吩基 H 1075 5_F cf3 C=C-2·噚唑基 H 1076 5-F cf3 C=C-2_嘧唑基 H 1077 5-F cf3 C=C-4-異崎唑基 H 1078 5_F cf3 C=C-2-咪唑基 H 1079 5-F cf3 CH2CH2-cycPr H 1080 5-F cf3 CH2CH2CH2CH2OH H 1081 5_F cf3 CH2CHrCH(OH)Me H 1082 5-F cf3 CH2CH2-Ph H 1083 5-F cf3 CH2CH2-(2-Cl)Ph H 1084 5-F cf3 CH2CH2-(3-Cl)Ph H 1085 5-F cf3 CH2CHr(4-Cl)Ph H 1086 5_F cf3 CH2CH2-(2-F)Ph H 1087 5-F cf3 CH2CH2-(3-F)Ph H 1088 5-F cf3 CH2CH2_(4-F)Ph H 1089 5-F cf3 CH2CHr(2-OH)Ph H 1090 5-F cf3 CH2CH2-(3-OH)Ph H 1091 5-F cf3 CH2CHr(4-OH)Ph H 1092 5-F cf3 CH2CH2-(2-OMe)Ph H 1093 5-F cf3 CH2CH2-(3-OMe)Ph H 1094 5-F cf3 CH2CH2-(4-OMe)Ph H 1095 5-F cf3 CH2CH2-(2-CN)Ph H 1096 5-F cf3 CH2CH2-(3-CN)Ph H 1097 5_F cf3 CH2CHr(4-CN)Ph H 1098 5-F cf3 CH2CH2-(2-N02)Ph H 1099 5-F cf3 CH2CH2-(3-N02)Ph H 1100 5-F cf3 CH2CH2-(4-N02)Ph H 1101 5-F cf3 CH2CHr(2-NH2)Ph H 1102 5-F cf3 CH2CH2-(3-NH2)Ph H 1103 5-F cf3 CH2CH2-(4-NH2)Ph H -96 - (請先閱讀背面之注意事項再填寫本頁) 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 587078 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明(94 ) 1104 5-F cf3 CH2CH2-(2-NMe2)Ph H 1105 5-F cf3 CH2CH2-(3-NMe2)Ph H 1106 5-F cf3 CH2CH2-(4-NMe2)Ph H 1107 5_F cf3 CH2CHr2-吡啶基 H 1108 5_F cf3 CH2CH2-3-吡啶基 H 1109 5-F cf3 CH2CH2-4-吡啶基 H 1110 5-F cf3 CH2CH2-2-呋喃基 H 1111 5-F cf3 CH2CH2-3-呋喃基 H 1112 5-F cf3 CH2CH2-2-嘍吩基 H 1113 5-F cf3 CH2CH2-3-嘧吩基 H 1114 5-F cf3 CH2CH2-2·崎唑基 H 1115 5-F cf3 CH2CHr2-嘍唑基 H 1116 5-F cf3 CH2CH2-4-異崎唑基 H 1117 5-F cf3 CH2CH2-2-咪唑基 H 1118 5-F cf3 C = C-cycPr ch3 1119 5-F cf3 C = C-Ph CHb 1120 5-F cf3 〇C-2-吡啶基 ch3 1121 5-F cf3 CeC-3-吡啶基 ch3 1122 5-F cf3 〇C-4-吡啶基 ch3 1123 5-F cf3 C Ξ C-2-咬喃基 ch3 1124 5-F cf3 C Ξ C-3·咬喃基 ch3 1125 5-F cf3 C Ξ C-2-遠吩基 ch3 1126 5-F cf3 C Ξ C-3-遠吩基 ch3 1127 5-F cf3 C=C-cycPr ch3 1128 5-F cf3 C=C-Ph ch3 1129 5-F cf3 C=C-2-吡啶基 ch3 1130 5-F cf3 C=C-3 比淀基 ch3 1131 5-F cf3 C=C-4-吡啶基 ch3 1132 5-F cf3 C=C-2_呋喃基 ch3 1133 5-F cf3 C=C-3-咬喃基 ch3 -97- (請先閱讀背面之注意事項再填寫本頁) 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 587078 經濟部中央標準局員工消費合作社印製 kl B7 五、發明説明(95 ) 1134 5-F cf3 C=C-2-p塞吩基 ch3 1135 5-F cf3 ch3 1136 5-F cf3 CH2CH2-cycPr ch3 請 1137 5-F cf3 CH2CH2-Ph ch3 先 閱 1138 5-F cf3 CH2CH2-2-吡啶基 ch3 讀 背 1139 5-F cf3 CH2CH2-3-吡啶基 ch3 面 1140 5-F cf3 CH2CH2-4-吡啶基 ch3 意 1141 5-F cf3 CH2CH2-2-呋喃基 ch3 Ψ 項 1142 5-F cf3 CH2CHr3-呋喃基 ch3 再 填、 1143 5-F cf3 CH2CH2-2-嘍吩基 ch3 本 1144 5-F cf3 CH2CHr3-噻吩基 ch3 頁 1145 5-F cf3 C = C-cycPr ch2ch3 1146 5-F cf3 C^C-Ph CH2CH3 1147 5-F cf3 C Ξ 淀基 ch2ch3 1148 5-F cf3 C Ξ C-3_#b^ 基 CH2CH3 1149 5-F cf3 C Ξ C-4-p比淀基 ch2ch3 1150 5-F cf3 C Ξ C-2-咬喃基 ch2ch3 1151 5-F cf3 C Ξ C-3-咬喃基 ch2ch3 1152 5-F cf3 C Ξ C-2-遠吩基 CH2CH3 1153 5-F cf3 C^C-3-嘍吩基 ch2ch3 1154 5-F cf3 C=C-cycPr ch2ch3 1155 5-F cf3 C=C-Ph CH2CH3 1156 5-F cf3 C=C-2-吡啶基 CH2CH3 1157 5_F cf3 C=C-3-p比淀基 ch2ch3 1158 5-F cf3 C=C_4w比淀基 CH2CH3 1159 5_F cf3 C=C-2-呋喃基 CH2CH3 1160 5_F cf3 〇C_3_呋喃基 ch2ch3 1161 5-F cf3 C=C-2-嘍吩基 CH2CH3 1162 5_F cf3 C=C-3-嘧吩基 CH2CH3 1163 5-F cf3 CH2CHrcycPr ch2ch3 -98- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 587078 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明(96 )1074 5_F cf3 C = C-3-pyrimidinyl H 1075 5_F cf3 C = C-2 · oxazolyl H 1076 5-F cf3 C = C-2_pyrazolyl H 1077 5-F cf3 C = C- 4-Isozazolyl H 1078 5_F cf3 C = C-2-imidazolyl H 1079 5-F cf3 CH2CH2-cycPr H 1080 5-F cf3 CH2CH2CH2CH2OH H 1081 5_F cf3 CH2CHrCH (OH) Me H 1082 5-F cf3 CH2CH2 -Ph H 1083 5-F cf3 CH2CH2- (2-Cl) Ph H 1084 5-F cf3 CH2CH2- (3-Cl) Ph H 1085 5-F cf3 CH2CHr (4-Cl) Ph H 1086 5_F cf3 CH2CH2- ( 2-F) Ph H 1087 5-F cf3 CH2CH2- (3-F) Ph H 1088 5-F cf3 CH2CH2_ (4-F) Ph H 1089 5-F cf3 CH2CHr (2-OH) Ph H 1090 5-F cf3 CH2CH2- (3-OH) Ph H 1091 5-F cf3 CH2CHr (4-OH) Ph H 1092 5-F cf3 CH2CH2- (2-OMe) Ph H 1093 5-F cf3 CH2CH2- (3-OMe) Ph H 1094 5-F cf3 CH2CH2- (4-OMe) Ph H 1095 5-F cf3 CH2CH2- (2-CN) Ph H 1096 5-F cf3 CH2CH2- (3-CN) Ph H 1097 5_F cf3 CH2CHr (4- CN) Ph H 1098 5-F cf3 CH2CH2- (2-N02) Ph H 1099 5-F cf3 CH2CH2- (3-N02) Ph H 1100 5-F cf3 CH2CH2- (4-N02) Ph H 1101 5-F cf3 CH2CHr (2-NH2) Ph H 1102 5-F cf3 CH2CH2- (3-NH2) Ph H 1103 5-F cf3 CH2CH2- (4-NH2) Ph H -96-(Please read the precautions on the back before filling (This page) This paper size is in accordance with Chinese National Standard (CNS) A4 (210X297 mm) 587078 Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs A7 B7 5. Invention Description (94) 1104 5-F cf3 CH2CH2- (2- NMe2) Ph H 1105 5-F cf3 CH2CH2- (3-NMe2) Ph H 1106 5-F cf3 CH2CH2- (4-NMe2) Ph H 1107 5_F cf3 CH2CHr2-pyridylH 1108 5_F cf3 CH2CH2-3-pyridylH 1109 5-F cf3 CH2CH2-4-pyridyl H 1110 5-F cf3 CH2CH2-2-furyl H 1111 5-F cf3 CH2CH2-3-furyl H 1112 5-F cf3 CH2CH2-2-fluorenyl H 1113 5-F cf3 CH2CH2-3-pyrimidinyl H 1114 5-F cf3 CH2CH2-2 · Zazolyl H 1115 5-F cf3 CH2CHr2-oxazolyl H 1116 5-F cf3 CH2CH2-4-Isozazolyl H 1117 5-F cf3 CH2CH2-2-imidazolyl H 1118 5-F cf3 C = C-cycPr ch3 1119 5-F cf3 C = C-Ph CHb 1120 5-F cf3 〇C-2-pyridyl ch3 1121 5- F cf3 CeC-3-pyridyl ch3 1122 5-F cf3 〇C-4-pyridyl ch3 1123 5-F cf3 C Ξ C-2-pyranyl ch3 1124 5-F cf3 C Ξ C-3 · bitan Radical ch3 1125 5-F cf3 C Ξ C-2-farphenyl ch3 1126 5-F cf3 C Ξ C-3-farphenyl ch3 1127 5-F cf3 C = C-cycPr c h3 1128 5-F cf3 C = C-Ph ch3 1129 5-F cf3 C = C-2-pyridyl ch3 1130 5-F cf3 C = C-3 than yodo ch3 1131 5-F cf3 C = C-4 -Pyridyl ch3 1132 5-F cf3 C = C-2_furanyl ch3 1133 5-F cf3 C = C-3-octanoyl ch3 -97- (Please read the precautions on the back before filling this page) This Paper size applies to Chinese National Standard (CNS) A4 (210X297 mm) 587078 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs Kl B7 V. Description of the invention (95) 1134 5-F cf3 C = C-2-p Base ch3 1135 5-F cf3 ch3 1136 5-F cf3 CH2CH2-cycPr ch3 Please 1137 5-F cf3 CH2CH2-Ph ch3 Read 1138 5-F cf3 CH2CH2-2-pyridyl ch3 Read back 1139 5-F cf3 CH2CH2- 3-pyridyl ch3 surface 1140 5-F cf3 CH2CH2-4-pyridyl ch3 meaning 1141 5-F cf3 CH2CH2-2-furyl ch3 Ψ item 1142 5-F cf3 CH2CHr3-furyl ch3 refill, 1143 5-F cf3 CH2CH2-2-fluorenyl ch3 Ben 1144 5-F cf3 CH2CHr3-thienyl ch3 Page 1145 5-F cf3 C = C-cycPr ch2ch3 1146 5-F cf3 C ^ C-Ph CH2CH3 1147 5-F cf3 C Ξ Yodo ch2ch3 1148 5-F cf3 C Ξ C-3_ # b ^ radical CH2CH3 1149 5-F cf3 C Ξ C-4-p than Yodo ch2ch3 1150 5-F cf3 C Ξ C-2-Oranyl ch2ch3 1151 5-F cf3 C Ξ C-3-Oranyl ch2ch3 1152 5-F cf3 C Ξ C-2- Farphenyl CH2CH3 1153 5-F cf3 C ^ C-3-fluorenyl ch2ch3 1154 5-F cf3 C = C-cycPr ch2ch3 1155 5-F cf3 C = C-Ph CH2CH3 1156 5-F cf3 C = C- 2-pyridyl CH2CH3 1157 5_F cf3 C = C-3-p ratio Yodo group ch2ch3 1158 5-F cf3 C = C_4w ratio Yodo group CH2CH3 1159 5_F cf3 C = C-2-furyl group CH2CH3 1160 5_F cf3 〇C_3_furan Ch2ch3 1161 5-F cf3 C = C-2-fluorenyl CH2CH3 1162 5_F cf3 C = C-3-pyrimidinyl CH2CH3 1163 5-F cf3 CH2CHrcycPr ch2ch3 -98- This paper is in accordance with the Chinese National Standard (CNS) A4 specification (210X297 mm) 587078 A7 B7 printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs 5. Description of the invention (96)
1164 5_F cf3 CH2CHrPh CH2CH3 1165 5-F cf3 CH2CH2-2-吡啶基 ch2ch3 1166 5-F cf3 CH2CH2-3-吡啶基 ch2ch3 1167 5-F cf3 CH2CHr4_吡啶基 ch2ch3 1168 5-F cf3 CH2CH2-2-呋喃基 CH2CH3 1169 5-F cf3 CH2CHr3-呋喃基 CH2CH3 1170 5-F cf3 CH2CH2-2-嘧吩基 CH2CH3 1171 5-F cf3 CH2CH2-3-嘧吩基 CH2CH3 1172 5-Cl,6-F cf3 C = C-cycPr H 1173 5-Cl,6-F cf3 C^C-Ph H 1174 5-Cl,6-F cf3 CeC-2-吡啶基 H 1175 5-Cl,6-F cf3 OC-3_吡啶基 H 1176 5_C1,6-F cf3 C Ξ CM-p比淀基 H 1177 5-Cl,6-F cf3 CeC-2-呋喃基 H 1178 5-Cl,6-F cf3 C^C-3-呋喃基 H 1179 5-Cl,6-F cf3 C Ξ C-2-p塞吩基 H 1180 5-Cl,6-F cf3 C = C-3-p塞吩基 H 1181 5-Cl,6-F cf3 C=C-cycPr H 1182 5-Cl,6-F cf3 C=C-Ph H 1183 5-Cl,6-F cf3 C=C-2-吡啶基 H 1184 5_C1,6-F cf3 C=C-3-吡啶基 H 1185 5-Cl,6-F cf3 C=C-4-p比淀基 H 1186 5-Cl,6-F cf3 C=C-2-咬喃基 H 1187 5-Cl,6-F cf3 C=C-3-呋喃基 H 1188 5-Cl,6-F cf3 C=C-2-p塞吩基 H 1189 5-Cl,6-F cf3 C=C-3-p塞吩基 H 1190 5-Cl,6-F cf3 CH2CH2-cycPr H 1191 5-Cl,6-F cf3 CH2CH2-Ph H 1192 5-Cl,6-F cf3 CH2CHr2-吡啶基 H 1193 5-Cl,6-F cf3 CH2CHr3-吡啶基 H (請先閱讀背面之注意事項再填寫本頁)1164 5_F cf3 CH2CHrPh CH2CH3 1165 5-F cf3 CH2CH2-2-pyridyl ch2ch3 1166 5-F cf3 CH2CH2-3-pyridyl ch2ch3 1167 5-F cf3 CH2CHr4_pyridyl ch2ch3 1168 5-F cf3 CH2CH2-2-furyl CH2CH3 1169 5-F cf3 CH2CHr3-furyl CH2CH3 1170 5-F cf3 CH2CH2-2-pyriminyl CH2CH3 1171 5-F cf3 CH2CH2-3-pyriminyl CH2CH3 1172 5-Cl, 6-F cf3 C = C- cycPr H 1173 5-Cl, 6-F cf3 C ^ C-Ph H 1174 5-Cl, 6-F cf3 CeC-2-pyridyl H 1175 5-Cl, 6-F cf3 OC-3_pyridyl H 1176 5_C1,6-F cf3 C Ξ CM-p than Yodo H 1177 5-Cl, 6-F cf3 CeC-2-furyl H 1178 5-Cl, 6-F cf3 C ^ C-3-furyl H 1179 5-Cl, 6-F cf3 C Ξ C-2-p selphenyl H 1180 5-Cl, 6-F cf3 C = C-3-p selphenyl H 1181 5-Cl, 6-F cf3 C = C-cycPr H 1182 5-Cl, 6-F cf3 C = C-Ph H 1183 5-Cl, 6-F cf3 C = C-2-pyridyl H 1184 5_C1, 6-F cf3 C = C-3- Pyridyl H 1185 5-Cl, 6-F cf3 C = C-4-p ratio HYdron H 1186 5-Cl, 6-F cf3 C = C-2-pyranyl H 1187 5-Cl, 6-F cf3 C = C-3-furanyl H 1188 5-Cl, 6-F cf3 C = C-2-p selphenyl H 1189 5-Cl, 6-F cf3 C = C-3-p selphenyl H 1190 5-Cl, 6-F cf3 CH2CH2-cycPr H 1191 5-Cl, 6-F cf3 CH2CH2-Ph H 1192 5-Cl, 6-F cf3 CH2CHr2-pyridyl H 1193 5-Cl, 6-F cf3 CH2CHr3-pyridyl H (Please read the back first (Notes to fill out this page)
、1T -99 - 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 587078 經濟部中央標準局員工消費合作社印製 Μ Β7 五、發明説明(97 ) 1194 5-Cl,6-F cf3 CH2CH2_4-吡啶基 H 1195 5-Cl,6-F cf3 CH2CH2-2-呋喃基 H 1196 5-Cl,6-F cf3 CH2CH2-3-呋喃基 H 1197 5-Cl,6-F cf3 CH2CH2-2·嘍吩基 H 1198 5-Cl,6-F cf3 CH2CH2-3-嘍吩基 H 1199 5-Cl,6-F cf3 C = C-cycPr ch3 1200 5-Cl,6_F cf3 C^C-Ph ch3 1201 5-Cl,6-F cf3 CeC-2-吡啶基 ch3 1202 5-Cl,6-F cf3 C = C-3-吡啶基 ch3 1203 5-Cl,6-F cf3 CeC-4-吡啶基 ch3 1204 5-Cl,6-F cf3 C Ξ C-2_咬喃基 ch3 1205 5-Cl,6-F cf3 C Ξ C-3-咬喃基 ch3 1206 5-Cl,6-F cf3 C^C-2-噻吩基 ch3 1207 5-Cl,6-F cf3 C = C-3-p塞吩基 ch3 1208 5-Cl,6-F cf3 C=C-cycPr ch3 1209 5-Cl,6-F cf3 C=C-Ph ch3 1210 5-Cl,6-F cf3 C=C-2-p比淀基 ch3 1211 5-Cl,6-F cf3 比淀基 ch3 1212 5-Cl,6-F cf3 C=C-4_p比咬基 ch3 1213 5-Cl,6-F cf3 C=C-2-呋喃基 ch3 1214 5-Cl,6-F cf3 C=C-3-咬喃基 ch3 1215 5-Cl,6-F cf3 C=C-2-p塞吩基 ch3 1216 5-Cl,6-F cf3 C=C-3-噻吩基 ch3 1217 5-Cl,6-F cf3 CH2CH2-cycPr ch3 1218 5-Cl,6-F cf3 CH2CH2-Ph ch3 1219 5-Cl,6-F cf3 CH2CHr2-吡啶基 ch3 1220 5-Cl,6-F cf3 CH2CH2-3-吡啶基 ch3 1221 5-Cl,6_F cf3 CH2CH2-4-吡啶基 ch3 1222 5-Cl,6-F cf3 CH2CH2-2·呋喃基 ch3 1223 5-Cl,6-F cf3 CH2CHr3-呋喃基 ch3 -100- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 587078 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明(98 ) 1224 5-Cl,6-F cf3 CH2CHr2·嘍吩基 ch3 1225 5-Cl,6-F cf3 CH2CH2-3·嘧吩基 ch3 1226 5-F,6-Cl cf3 C = C-cycPr H 1227 5-F,6-Cl cf3 C^C-Ph H 1228 5-F,6-Cl cf3 CeC-2-吡啶基 H 1229 5-F,6-Cl cf3 CeC-3-吡啶基 H 1230 5-F,6-Cl cf3 CeC-4-p比淀基 H 1231 5-F,6-Cl cf3 C = C-2-咬喃基 H 1232 5-F,6-Cl cf3 C Ξ C-3-咬喃基 H 1233 5-F,6-Cl cf3 C Ξ C-2-p塞吩基 H 1234 5-F,6-Cl cf3 C Ξ C-3-p塞吩基 H 1235 5-F,6-Cl cf3 C=C_cycPr H 1236 5-F,6-Cl cf3 C=C_Ph H 1237 5-F,6-Cl cf3 C=C-2-吡啶基 H 1238 5-F,6-Cl cf3 C=C-3-吡啶基 H 1239 5-F,6-Cl cf3 C=C-4-峨淀基 H 1240 5-F,6-Cl cf3 C=C-2-呋喃基 H 1241 5-F,6-Cl cf3 C=C-3-咬喃基 H 1242 5-F,6-Cl cf3 C=C_2-嘧吩基 H 1243 5-F,6-Cl cf3 C=C-3-p塞吩基 H 1244 5-F,6-Cl cf3 CH2CH2-cycPr H 1245 5-F,6-Cl cf3 CH2CH2-Ph H 1246 5-F,6-Cl cf3 CH2CHr2-吡啶基 H 1247 5-F,6-Cl cf3 CH2CH2-3-毗啶基 H 1248 5-F,6-Cl cf3 CH2CHr4-吡啶基 H 1249 5-F,6-Cl cf3 CH2CHr2-呋喃基 H 1250 5-F,6-Cl cf3 CH2CH2-3-呋喃基 H 1251 5-F,6-Cl cf3 CH2CH2_2_嘧吩基 H 1252 5-F,6-Cl cf3 CH2CHr3-嘍吩基 H 1253 5-F,6-Cl cf3 C = C-cycPr ch3 (請先閱讀背面之注意事項再填寫本頁)、 1T -99-This paper size is applicable to China National Standard (CNS) A4 (210X297mm) 587078 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs Β7 V. Description of the Invention (97) 1194 5-Cl, 6-F cf3 CH2CH2_4-pyridyl H 1195 5-Cl, 6-F cf3 CH2CH2-2-furyl H 1196 5-Cl, 6-F cf3 CH2CH2-3-furyl H 1197 5-Cl, 6-F cf3 CH2CH2-2 · Fenyl H 1198 5-Cl, 6-F cf3 CH2CH2-3-Fenyl H 1199 5-Cl, 6-F cf3 C = C-cycPr ch3 1200 5-Cl, 6_F cf3 C ^ C-Ph ch3 1201 5-Cl, 6-F cf3 CeC-2-pyridyl ch3 1202 5-Cl, 6-F cf3 C = C-3-pyridyl ch3 1203 5-Cl, 6-F cf3 CeC-4-pyridyl ch3 1204 5-Cl, 6-F cf3 C Ξ C-2_branyl group ch3 1205 5-Cl, 6-F cf3 C Ξ C-3-branyl group ch3 1206 5-Cl, 6-F cf3 C ^ C -2-thienyl ch3 1207 5-Cl, 6-F cf3 C = C-3-p selphenyl ch3 1208 5-Cl, 6-F cf3 C = C-cycPr ch3 1209 5-Cl, 6-F cf3 C = C-Ph ch3 1210 5-Cl, 6-F cf3 C = C-2-p than Yodo ch3 1211 5-Cl, 6-F cf3 than Yodo ch3 1212 5-Cl, 6-F cf3 C = C-4_p than chrysyl ch3 1213 5-Cl, 6-F cf3 C = C-2-furyl ch3 1214 5-Cl, 6-F cf3 C = C-3- cytyl ch3 1215 5-Cl, 6-F cf3 C = C-2-p sephenyl ch3 1216 5-Cl, 6-F cf3 C = C-3-thienyl ch3 1217 5-Cl, 6-F cf3 CH2CH2-cycPr ch3 1218 5-Cl, 6-F cf3 CH2CH2-Ph ch3 1219 5-Cl, 6-F cf3 CH2CHr2-pyridyl ch3 1220 5-Cl, 6-F cf3 CH2CH2-3-pyridyl ch3 1221 5-Cl, 6_F cf3 CH2CH2-4-pyridyl ch3 1222 5-Cl, 6-F cf3 CH2CH2-2 · furanyl ch3 1223 5-Cl, 6-F cf3 CH2CHr3-furanyl ch3 -100- This paper is in accordance with Chinese national standards (CNS ) A4 specification (210X297 mm) 587078 Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs A7 B7 V. Description of the invention (98) 1224 5-Cl, 6-F cf3 CH2CHr2 · fenphenyl ch3 1225 5-Cl, 6- F cf3 CH2CH2-3 · pyrimidinyl ch3 1226 5-F, 6-Cl cf3 C = C-cycPr H 1227 5-F, 6-Cl cf3 C ^ C-Ph H 1228 5-F, 6-Cl cf3 CeC -2-pyridyl H 1229 5-F, 6-Cl cf3 CeC-3-pyridyl H 1230 5-F, 6-Cl cf3 CeC-4-p than Hyl 1231 5-F, 6-Cl cf3 C = C-2-Cyranyl H 1232 5-F, 6-Cl cf3 C Ξ C-3-Cyranyl H 1233 5-F, 6-Cl cf3 C Ξ C-2-p Cephenyl H 1234 5 -F, 6-Cl cf3 C Ξ C-3-p sephenyl H 1235 5-F, 6-Cl cf3 C = C_cycPr H 1236 5-F, 6-Cl cf3 C = C_Ph H 1237 5-F, 6-Cl cf3 C = C-2-pyridyl H 1238 5-F, 6-Cl cf3 C = C-3-pyridyl H 1239 5-F, 6-Cl cf3 C = C-4-Eodoyl H 1240 5-F, 6-Cl cf3 C = C-2-furyl H 1241 5-F, 6-Cl cf3 C = C -3-octanoyl H 1242 5-F, 6-Cl cf3 C = C_2-pyriminyl H 1243 5-F, 6-Cl cf3 C = C-3-p selphenyl H 1244 5-F, 6 -Cl cf3 CH2CH2-cycPr H 1245 5-F, 6-Cl cf3 CH2CH2-Ph H 1246 5-F, 6-Cl cf3 CH2CHr2-pyridyl H 1247 5-F, 6-Cl cf3 CH2CH2-3-pyridinyl H 1248 5-F, 6-Cl cf3 CH2CHr4-pyridyl H 1249 5-F, 6-Cl cf3 CH2CHr2-furyl H 1250 5-F, 6-Cl cf3 CH2CH2-3-furyl H 1251 5-F, 6-Cl cf3 CH2CH2_2_pyriminyl H 1252 5-F, 6-Cl cf3 CH2CHr3-fluorenyl H 1253 5-F, 6-Cl cf3 C = C-cycPr ch3 (Please read the precautions on the back before filling (This page)
、1T ——. -101 - 本紙張尺度適用中國國家標準(CNS ) Α4規格(210X 297公釐) 587078 經濟部中央標準局員工消費合作社印製 Μ Β7 99 五、發明説明()、 1T ——. -101-This paper size is applicable to the Chinese National Standard (CNS) Α4 specification (210X 297 mm) 587078 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs M Β7 99 V. Description of the invention ()
1254 5-F,6-Cl cf3 C = C_Ph ch3 1255 5-F,6-Cl cf3 C Ξ C-2-p比淀基 ch3 1256 5-F,6-Cl cf3 C = C-3-吡啶基 ch3 1257 5-F,6-Cl cf3 CeC-4-吡啶基 ch3 1258 5-F,6-Cl cf3 C = C-2-呋喃基 ch3 1259 5-F,6-Cl cf3 C = C-3-呋喃基 ch3 1260 5-F,6-Cl cf3 C Ξ C-2-p塞吩基 ch3 1261 5-F,6-Cl cf3 C = C-3-嘍吩基 ch3 1262 5-F,6-Cl cf3 C=C-cycPr ch3 1263 5-F,6-Cl cf3 C=C-Ph ch3 1264 5-F,6-Cl cf3 C=C-2-吡啶基 ch3 1265 5-F,6-Cl cf3 C=C-3-吡啶基 ch3 1266 5-F,6-Cl cf3 C=C-4-吡啶基 ch3 1267 5-F,6-Cl cf3 C=C-2-咬喃基 ch3 1268 5-F,6-Cl cf3 C=C-3-咬喃基 ch3 1269 5-F,6-Cl cf3 C=C-2-^ 吩基 ch3 1270 5-F,6-Cl cf3 C=C-3-嘧吩基 ch3 1271 5-F,6-Cl cf3 CH2CH2-cycPr ch3 1272 5-F,6-Cl cf3 CH2CH2-Ph ch3 1273 5-F,6-Cl cf3 CH2CHr2-吡啶基 ch3 1274 5-F,6-Cl cf3 CH2CH2-3-吡啶基 ch3 1275 5-F,6-Cl cf3 CH2CH2-4-吡啶基 ch3 1276 5-F,6-Cl cf3 CH2CH2-2-呋喃基 ch3 1277 5-F,6-Cl cf3 CH2CH2_3-呋喃基 ch3 1278 5-F,6-Cl cf3 CH2CH2-2-嘧吩基 ch3 1279 5-F,6-Cl cf3 CH2CH2-3-嘧吩基 ch3 1280 6_C1,8-F cf3 C = C-cycPr H 1281 6-Cl,8_F cf3 C^C-Ph H 1282 6-Cl,8-F cf3 CeC_2-吡啶基 H 1283 6-Cl,8 -F cf3 C Ξ C_3_p比淀基 H (請先閱讀背面之注意事項再填寫本頁) -102- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 587078 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明(1(K)) 1284 6-Cl,8-F cf3 c三C-4·吡啶基 H 1285 6-Cl,8_F cf3 C = C-2-咬喃基 H 1286 6-Cl,8-F cf3 C Ξ C-3-咬喃基 H 1287 6_C1,8-F cf3 C^C-2-嘍吩基 H 1288 6_C1,8-F cf3 C = C-3-p塞吩基 H 1289 6-Cl,8-F cf3 C=C-cycPr H 1290 6_C1,8_F cf3 C=C-Ph H 1291 6_C1,8_F cf3 C=C_2_p比淀基 H 1292 6_C1,8-F cf3 C=C-3-吡啶基 H 1293 6-Cl,8-F cf3 C=C-4^比淀基 H 1294 6-Cl,8-F cf3 C=C-2-咬喃基 H 1295 6-Cl,8-F cf3 C=C-3-呋喃基 H 1296 6_C1,8_F cf3 C=C-2-嘍吩基 H 1297 6_C1,8_F cf3 C=C-3-嘧吩基 H 1298 6-Cl,8-F cf3 CH2CH2-cycPr H 1299 6-Cl,8_F cf3 CH2CH2-Ph H 1300 6-Cl,8-F cf3 CH2CH2-2-吡啶基 H 1301 6_C1,8-F cf3 CH2CH2-3-吡啶基 H 1302 6_C1,8-F cf3 CH2CH2-4·吡啶基 H 1303 6-Cl,8_F cf3 CH2CHr2-呋喃基 H 1304 6-Cl,8-F cf3 CH2CH2-3-呋喃基 H 1305 6-Cl,8-F cf3 CH2CH2-2-^ 吩基 H 1306 6_C1,8-F cf3 CH2CHr3-嘧吩基 H 1307 6_C1,8_F cf3 C = C-cycPr ch3 1308 6-Cl,8-F cf3 C^C-Ph ch3 1309 6-Cl,8-F cf3 CeC-2-吡啶基 ch3 1310 6_C1,8_F cf3 C = C-3-p比淀基 ch3 1311 6-Cl,8-F cf3 Ce〇4-p比淀基 ch3 1312 6-Cl,8-F cf3 C Ξ C-2-咬喃基 ch3 1313 6-Cl,8-F cf3 C Ξ C-3-咬喃基 ch3 (請先閱讀背面之注意事項再填寫本頁) -103- 本紙張尺度適用中國國家標準(CNS ) Α4規格(210Χ 297公釐) 587078 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明(1()1)1254 5-F, 6-Cl cf3 C = C_Ph ch3 1255 5-F, 6-Cl cf3 C Ξ C-2-p than ytyl ch3 1256 5-F, 6-Cl cf3 C = C-3-pyridyl ch3 1257 5-F, 6-Cl cf3 CeC-4-pyridyl ch3 1258 5-F, 6-Cl cf3 C = C-2-furyl ch3 1259 5-F, 6-Cl cf3 C = C-3- Furyl ch3 1260 5-F, 6-Cl cf3 C Ξ C-2-p sephenyl ch3 1261 5-F, 6-Cl cf3 C = C-3-fluorenyl ch3 1262 5-F, 6-Cl cf3 C = C-cycPr ch3 1263 5-F, 6-Cl cf3 C = C-Ph ch3 1264 5-F, 6-Cl cf3 C = C-2-pyridyl ch3 1265 5-F, 6-Cl cf3 C = C-3-pyridyl ch3 1266 5-F, 6-Cl cf3 C = C-4-pyridyl ch3 1267 5-F, 6-Cl cf3 C = C-2-pyranyl ch3 1268 5-F, 6-Cl cf3 C = C-3-pyranyl ch3 1269 5-F, 6-Cl cf3 C = C-2- ^ phenyl ch3 1270 5-F, 6-Cl cf3 C = C-3-pyrimidine Ch3 1271 5-F, 6-Cl cf3 CH2CH2-cycPr ch3 1272 5-F, 6-Cl cf3 CH2CH2-Ph ch3 1273 5-F, 6-Cl cf3 CH2CHr2-pyridyl ch3 1274 5-F, 6-Cl cf3 CH2CH2-3-pyridyl ch3 1275 5-F, 6-Cl cf3 CH2CH2-4-pyridyl ch3 1276 5-F, 6-Cl cf3 CH2CH2-2-furyl ch3 1277 5-F, 6-Cl cf3 CH2CH2_3 -Furyl ch3 1278 5-F, 6-Cl cf3 CH2CH2-2-pyrimidine ch3 1279 5-F, 6-Cl cf3 CH2CH2-3-pyrimyl ch3 1280 6_C1, 8-F cf3 C = C-cycPr H 1281 6-Cl, 8_F cf3 C ^ C-Ph H 1282 6-Cl, 8 -F cf3 CeC_2-pyridyl H 1283 6-Cl, 8 -F cf3 C Ξ C_3_p than Yodo H (Please read the notes on the back before filling this page) -102- This paper size applies to Chinese National Standards (CNS) A4 specifications (210X297 mm) 587078 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Invention Description (1 (K)) 1284 6-Cl, 8-F cf3 c Tri-C-4 · pyridyl H 1285 6 -Cl, 8_F cf3 C = C-2-octyl group H 1286 6-Cl, 8-F cf3 C Ξ C-3-octyl group H 1287 6_C1,8-F cf3 C ^ C-2-fluorenyl group H 1288 6_C1, 8-F cf3 C = C-3-p sedenyl H 1289 6-Cl, 8-F cf3 C = C-cycPr H 1290 6_C1, 8_F cf3 C = C-Ph H 1291 6_C1, 8_F cf3 C = C_2_p than Yodo H 1292 6_C1,8-F cf3 C = C-3-pyridyl H 1293 6-Cl, 8-F cf3 C = C-4 ^ Yodo H 1294 6-Cl, 8-F cf3 C = C-2-octanoyl H 1295 6-Cl, 8-F cf3 C = C-3-furanyl H 1296 6_C1,8_F cf3 C = C-2-fluorenyl H 1297 6_C1, 8_F cf3 C = C-3-pyridinyl H 1298 6-Cl, 8-F cf3 CH2CH2-cycPr H 1299 6-Cl , 8_F cf3 CH2CH2-Ph H 1300 6-Cl, 8-F cf3 CH2CH2-2-pyridylH 1301 6_C1,8-F cf3 CH2CH2-3-pyridylH 1302 6_C1,8-F cf3 CH2CH2-4 · pyridyl H 1303 6-Cl, 8_F cf3 CH2CHr2-furyl H 1304 6-Cl, 8-F cf3 CH2CH2-3-furanyl H 1305 6-Cl, 8-F cf3 CH2CH2-2- ^ phenyl H 1306 6_C1, 8 -F cf3 CH2CHr3-pyridinyl H 1307 6_C1,8_F cf3 C = C-cycPr ch3 1308 6-Cl, 8-F cf3 C ^ C-Ph ch3 1309 6-Cl, 8-F cf3 CeC-2-pyridyl ch3 1310 6_C1, 8_F cf3 C = C-3-p ratio Yodo group ch3 1311 6-Cl, 8-F cf3 Ce〇4-p ratio Yodo group ch3 1312 6-Cl, 8-F cf3 C Ξ C-2- Chrysyl ch3 1313 6-Cl, 8-F cf3 C Ξ C-3-Chrysyl ch3 (Please read the notes on the back before filling out this page) -103- This paper size applies to China National Standard (CNS) Α4 Specifications (210 × 297 mm) 587078 Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs A7 B7 V. Invention Description (1 () 1)
1314 6-Cl,8_F cf3 C Ξ C-2-p塞吩基 ch3 1315 6-Cl,8-F cf3 OC-3-嘧吩基 ch3 1316 6-Cl,8-F cf3 C=C-cycPr ch3 1317 6-Cl,8-F cf3 C=C-Ph ch3 1318 6-Cl,8-F cf3 C=C-2-吡啶基 ch3 1319 6-Cl,8-F cf3 C=C-3-p比淀基 ch3 1320 6-Cl,8-F cf3 C=C-4-p比淀基 ch3 1321 6-Cl,8_F cf3 C=C-2-呋喃基 ch3 1322 6_C1,8-F cf3 C=C-3·呋喃基 ch3 1323 6-Cl,8-F cf3 C=C-2-嘍吩基 ch3 1324 6-Cl,8-F cf3 C=C-3-p塞吩基 ch3 1325 6_C1,8-F cf3 CH2CH2_cycPr ch3 1326 6_C1,8-F cf3 CH2CH2-Ph ch3 1327 6-Cl,8-F cf3 CH2CHr2-吡啶基 ch3 1328 6-Cl,8-F cf3 CH2CH2-3-吡啶基 ch3 1329 6-Cl,8-F cf3 CH2CH2-4-吡啶基 ch3 1330 6-Cl,8-F cf3 CH2CH2-2-呋喃基 ch3 1331 6_C1,8_F cf3 CH2CH2_3-呋喃基 ch3 1332 6-Cl,8-F cf3 CH2CH2-2-嘧吩基 ch3 1333 6-Cl,8-F cf3 CH2CH2-3·嘧吩基 ch3 1334 6-CH3 cf3 C^C-cycPr H 1335 6_CH3 cf3 C^C-Ph H 1336 6-CH3 cf3 C三C-2_ 口比淀基 H 1337 6-CH3 cf3 C Ξ C-3-^比淀基 H 1338 6-CH3 cf3 CeC-4_吡啶基 H 1339 6-CH3 cf3 C Ξ C-2·咬喃基 H 1340 6-CH3 cf3 C Ξ C-3-咬喃基 H 1341 6-CH3 cf3 C Ξ C-2-ρ塞吩基 H 1342 6-CH3 cf3 C = C-3-嘧吩基 H 1343 6-CH3 cf3 C=C-cycPr H (請先閲讀背面之注意事項再填寫本頁) -104- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X 297公釐) 587078 經濟部中央標準局員工消費合作社印製 Μ Β7 102 五、發明説明() 1344 6-CH3 CF3 C=C-Ph H 1345 6-CH3 cf3 C=C-2-p比淀基 H 1346 6-CH3 cf3 C=C-3-p比淀基 H 1347 6-CH3 cf3 C=C-4-#b 淀基 H 1348 6-CH3 cf3 C=C-2-咬喃基 H 1349 6-CH3 cf3 C=C-3-呋喃基 H 1350 6-CH3 cf3 C=C-2-遠吩基 H 1351 6-CH3 cf3 C=C-3-嘧吩基 H 1352 6-CH3 cf3 CH2CH2-cycPr H 1353 6-CH3 cf3 CH2CH2-Ph H 1354 6-CH3 cf3 CH2CHr2-吡啶基 H 1355 6-CH3 cf3 CH2CH2-3-吡啶基 H 1356 6-CH3 cf3 CH2CH2-4-吡啶基 H 1357 6-CH3 cf3 CH2CH2-2_呋喃基 H 1358 6-CH3 cf3 CH2CH2-3-呋喃基 H 1359 6-CH3 cf3 CH2CHr2_嘍吩基 H 1360 6-CH3 cf3 CH2CH2-3·嘧吩基 H 1361 6-CH3 cf3 C = C-cycPr ch3 1362 6-CH3 cf3 C^C-Ph ch3 1363 6-CH3 cf3 C Ξ C-2-p比淀基 ch3 1364 6-CH3 cf3 C = C-3·峨淀基 ch3 1365 6-CH3 cf3 C Ξ C-4-p比淀基 ch3 1366 6-CH3 cf3 C Ξ C-2-咬喃基 ch3 1367 6-CH3 cf3 C = C-3-呋喃基 ch3 1368 6-CH3 cf3 C Ξ C-2-p塞吩基 ch3 1369 6-CH3 cf3 C Ξ C_3-遠吩基 ch3 1370 6-CH3 cf3 C=C-cycPr ch3 1371 6-CH3 cf3 C=C-Ph ch3 1372 6-CH3 cf3 C=C-2-吡啶基 ch3 1373 6-CH3 cf3 C=C-3-吡啶基 ch3 (請先閱讀背面之注意事項再填寫本頁) -105- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 587078 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明(1()3)1314 6-Cl, 8_F cf3 C Ξ C-2-p sephenyl ch3 1315 6-Cl, 8-F cf3 OC-3-pyrimyl ch3 1316 6-Cl, 8-F cf3 C = C-cycPr ch3 1317 6-Cl, 8-F cf3 C = C-Ph ch3 1318 6-Cl, 8-F cf3 C = C-2-pyridyl ch3 1319 6-Cl, 8-F cf3 C = C-3-p ratio Yodo ch3 1320 6-Cl, 8-F cf3 C = C-4-p than Yodo ch3 1321 6-Cl, 8_F cf3 C = C-2-furyl ch3 1322 6_C1, 8-F cf3 C = C- 3 · furanyl ch3 1323 6-Cl, 8-F cf3 C = C-2-fluorenyl ch3 1324 6-Cl, 8-F cf3 C = C-3-p cephenyl ch3 1325 6_C1,8-F cf3 CH2CH2_cycPr ch3 1326 6_C1,8-F cf3 CH2CH2-Ph ch3 1327 6-Cl, 8-F cf3 CH2CHr2-pyridyl ch3 1328 6-Cl, 8-F cf3 CH2CH2-3-pyridyl ch3 1329 6-Cl, 8 -F cf3 CH2CH2-4-pyridyl ch3 1330 6-Cl, 8-F cf3 CH2CH2-2-furyl ch3 1331 6_C1, 8_F cf3 CH2CH2_3-furyl ch3 1332 6-Cl, 8-F cf3 CH2CH2-2-pyrimidin Phenyl ch3 1333 6-Cl, 8-F cf3 CH2CH2-3 · Pyramidyl ch3 1334 6-CH3 cf3 C ^ C-cycPr H 1335 6_CH3 cf3 C ^ C-Ph H 1336 6-CH3 cf3 C tri-C-2_ Methylpyridyl H 1337 6-CH3 cf3 C Ξ C-3- ^ Pyridyl H 1338 6-CH3 cf3 CeC-4_pyridyl H 1339 6-CH3 cf3 C Ξ C-2 H 1340 6-CH3 cf3 C Ξ C-3-Oranyl H 1341 6-CH3 cf3 C Ξ C-2-ρ Cephenyl H 1342 6-CH3 cf3 C = C-3-Pyridinyl H 1343 6 -CH3 cf3 C = C-cycPr H (Please read the notes on the back before filling out this page) -104- This paper size applies to China National Standard (CNS) A4 (210X 297 mm) 587078 Employees of the Central Standards Bureau of the Ministry of Economic Affairs Printed by the consumer cooperatives Β7 102 V. Description of the invention () 1344 6-CH3 CF3 C = C-Ph H 1345 6-CH3 cf3 C = C-2-p than Yodo H 1346 6-CH3 cf3 C = C-3 -p than Dynyl H 1347 6-CH3 cf3 C = C-4- # b Dynyl H 1348 6-CH3 cf3 C = C-2-ylanyl H 1349 6-CH3 cf3 C = C-3-furanyl H 1350 6-CH3 cf3 C = C-2-distenyl H 1351 6-CH3 cf3 C = C-3-pyriminyl H 1352 6-CH3 cf3 CH2CH2-cycPr H 1353 6-CH3 cf3 CH2CH2-Ph H 1354 6-CH3 cf3 CH2CHr2-pyridyl H 1355 6-CH3 cf3 CH2CH2-3-pyridyl H 1356 6-CH3 cf3 CH2CH2-4-pyridyl H 1357 6-CH3 cf3 CH2CH2-2_furyl H 1358 6-CH3 cf3 CH2CH2-3-furanyl H 1359 6-CH3 cf3 CH2CHr2_fluorenyl H 1360 6-CH3 cf3 CH2CH2-3pyriminyl H 1361 6-CH3 cf3 C = C-cycPr ch3 1362 6-CH 3 cf3 C ^ C-Ph ch3 1363 6-CH3 cf3 C Ξ C-2-p ratio Yodo ch3 1364 6-CH3 cf3 C = C-3 · Edo ch3 1365 6-CH3 cf3 C Ξ C-4- p ratio ytyl ch3 1366 6-CH3 cf3 C Ξ C-2-ylfuranyl ch3 1367 6-CH3 cf3 C = C-3-furyl ch3 1368 6-CH3 cf3 C Ξ C-2-p cephenyl ch3 1369 6-CH3 cf3 C Ξ C_3-distenyl ch3 1370 6-CH3 cf3 C = C-cycPr ch3 1371 6-CH3 cf3 C = C-Ph ch3 1372 6-CH3 cf3 C = C-2-pyridyl ch3 1373 6-CH3 cf3 C = C-3-pyridyl ch3 (Please read the notes on the back before filling out this page) -105- This paper size applies to China National Standard (CNS) A4 (210X297 mm) 587078 Central Ministry of Economic Affairs Printed by the Consumer Bureau of Standards Bureau A7 B7 V. Description of Invention (1 () 3)
1374 6-CH3 cf3 C=C-4-吡啶基 ch3 1375 6-CH3 cf3 C=C-2-咬喃基 ch3 1376 6-CH3 cf3 C=C-3-咬喃基 ch3 1377 6-CH3 cf3 C=C-2-嘍吩基 ch3 1378 6-CH3 cf3 C=C-3-p塞吩基 ch3 1379 6-CH3 cf3 CH2CH2-cycPr ch3 1380 6-CH3 cf3 CH2CH2-Ph ch3 1381 6-CH3 cf3 CH2CH2-2-吡啶基 ch3 1382 6-CH3 cf3 CH2CH2-3-毗啶基 ch3 1383 6-CH3 cf3 CH2CH2-4-吡啶基 ch3 1384 6-CH3 cf3 CH2CHr2-呋喃基 ch3 1385 6-CH3 cf3 CH2CH2-3-呋喃基 ch3 1386 6-CH3 cf3 CH2CH2-2-噻吩基 ch3 1387 6_CH3 cf3 CH2CH2-3-嘧吩基 ch3 1388 6-COCH3 cf3 C = C-cycPr H 1389 6-COCH3 cf3 C-C-Ph H 1390 6-COCH3 cf3 OC-2-吡啶基 H 1391 6-COCH3 cf3 C^C-3-p比咬基 H 1392 6-COCH3 cf3 Ce〇4-峨淀基 H 1393 6-COCH3 cf3 C Ξ C-2·咬喃基 H 1394 6-COCH3 cf3 C Ξ C-3·咬喃基 H 1395 6-COCH3 cf3 C Ξ C-2-p塞吩基 H 1396 6-COCH3 cf3 C Ξ C-3_喧吩基 H 1397 6-NH2 cf3 C = C-cycPr H 1398 6-NH2 cf3 C^C-Ph H 1399 6-NH2 cf3 C Ξ C-2-p比咬基 H 1400 6-NH2 cf3 03-外匕淀基 H 1401 6-NH2 cf3 C e 〇4-p比淀基 H 1402 6_NH2 cf3 C = C-2-呋喃基 H 1403 6-NH2 cf3 C Ξ C-3-咬喃基 H (請先閱讀背面之注意事項再填寫本頁) -106- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 587078 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明(1〇4 )1374 6-CH3 cf3 C = C-4-pyridyl ch3 1375 6-CH3 cf3 C = C-2-pyranyl ch3 1376 6-CH3 cf3 C = C-3-pyranyl ch3 1377 6-CH3 cf3 C = C-2-fluorenyl ch3 1378 6-CH3 cf3 C = C-3-p phenenyl ch3 1379 6-CH3 cf3 CH2CH2-cycPr ch3 1380 6-CH3 cf3 CH2CH2-Ph ch3 1381 6-CH3 cf3 CH2CH2- 2-pyridyl ch3 1382 6-CH3 cf3 CH2CH2-3-pyrimidyl ch3 1383 6-CH3 cf3 CH2CH2-4-pyridyl ch3 1384 6-CH3 cf3 CH2CHr2-furyl ch3 1385 6-CH3 cf3 CH2CH2-3-furan Ch3 1386 6-CH3 cf3 CH2CH2-2-thienyl ch3 1387 6_CH3 cf3 CH2CH2-3-pyriminyl ch3 1388 6-COCH3 cf3 C = C-cycPr H 1389 6-COCH3 cf3 CC-Ph H 1390 6-COCH3 cf3 OC-2-pyridyl H 1391 6-COCH3 cf3 C ^ C-3-p than octyl H 1392 6-COCH3 cf3 Ce〇4-erodoyl H 1393 6-COCH3 cf3 C Ξ C-2 H 1394 6-COCH3 cf3 C Ξ C-3 · Oranyl H 1395 6-COCH3 cf3 C Ξ C-2-p sedenyl H 1396 6-COCH3 cf3 C Ξ C-3_sulfenyl H 1397 6- NH2 cf3 C = C-cycPr H 1398 6-NH2 cf3 C ^ C-Ph H 1399 6-NH2 cf3 C Ξ C-2-p specific bite group H 1400 6-NH2 cf3 03-outer base H 1401 6- NH2 cf3 C e 〇4-p ratio Base H 1402 6_NH2 cf3 C = C-2-furyl H 1403 6-NH2 cf3 C Ξ C-3-branyl H (Please read the notes on the back before filling out this page) -106- This paper size is applicable to China National Standard (CNS) A4 specification (210X297 mm) 587078 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Invention Description (104)
1404 6_NH2 cf3 C ^ C-2-遠吩基 H 1405 6-NH2 cf3 C^C-3e塞吩基 H 1406 6-NMe2 cf3 C = C-cycPr H 1407 6-NMe2 cf3 C^C-Ph H 1408 6-NMe2 cf3 C Ξ C-2-p比淀基 H 1409 6-NMe2 cf3 Ce〇3_峨淀基 H 1410 6-NMe2 cf3 Ce〇4-p比淀基 H 1411 6-NMe2 cf3 C Ξ C_2-咬喃基 H 1412 6-NMe2 cf3 C Ξ C-3-咬喃基 H 1413 6-NMe2 cf3 C^C-2-嘧吩基 H 1414 6-NMe2 cf3 C Ξ C-3-p塞吩基 H 1415 7-C1 cf3 C = C-cycPr H 1416 7-C1 cf3 C^C-Ph H 1417 7-C1 cf3 C = 02-ρ比淀基 H 1418 7-C1 cf3 CeC-3-吡啶基 H 1419 7-C1 cf3 C ξ C-4-峨淀基 H 1420 7-C1 cf3 C = C-2-咬喃基 H 1421 7-C1 cf3 C Ξ C-3-咬喃基 H 1422 7-C1 cf3 C = C-2-嘍吩基 H 1423 7-C1 cf3 C Ξ C-3-ρ塞吩基 H 1424 5,6-0CH20- cf3 C = C-cycPr H 1425 5,6-0CH20- cf3 C^CCH2CH2OH H 1426 5,6-0CH20- cf3 C^C-CH(OH)Me H 1427 5,6-0CH20- cf3 C^C-Ph H 1428 5,6-0CH20- cf3 C = C-(2-Cl)Ph H 1429 5,6_0CH20- cf3 C^C-(3-Cl)Ph H 1430 5,6-0CH20- cf3 C^C-(4-Cl)Ph H 1431 5,6_0CH20- cf3 C = C-(2-F)Ph H 1432 5,6-0CH20- cf3 C^C-(3-F)Ph H 1433 5,6-0CH20- cf3 C^C-(4-F)Ph H (請先閱讀背面之注意事項再填寫本頁) -107- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 587078 經濟部中央標準局員工消費合作社印製 A7 B7 105 五、發明説明() 1434 5,6-0CH20- cf3 C^C-(2-OH)Ph Η 1435 5,6-0CH20- cf3 C = C-(3-〇H)Ph Η 1436 5,6-0CH20- cf3 C^C-(4-OH)Ph Η 1437 5,6-0CH20- cf3 C^C-(2-OMe)Ph Η 1438 5,6-0CH20- cf3 C^C-(3-OMe)Ph Η 1439 5,6-0CH20- cf3 C = C-(4-OMe)Ph Η 1440 5,6-0CH20- cf3 C = C-(2-CN)Ph Η 1441 5,6-0CH20- cf3 C^C-(3-CN)Ph Η 1442 5,6-0CH20- cf3 C^C-(4-CN)Ph Η 1443 5,6-0CH20- cf3 C 三 C-(2-N02)Ph Η 1444 5,6-0CH20- cf3 C^C-(3-N02)Ph Η 1445 5,6-0CH20- cf3 〇C-(4-N02)Ph Η 1446 5,6_0CH20· cf3 C^C-(2-NH2)Ph Η 1447 5,6-0CH20- cf3 C^C-(3-NH2)Ph Η 1448 5,6-0CH20- cf3 C^C-(4-NH2)Ph Η 1449 5,6-0CH20- cf3 C^C-(2-NMe2)Ph Η 1450 5,6-0CH20- cf3 C 三 C-(3_NMe2)Ph Η 1451 5,6-0CH20- cf3 C^C-(4-NMe2)Ph Η 1452 5,6-0CH20- cf3 CeC_2·吡啶基 Η 1453 5,6-0CH20- cf3 C Ξ C-2-p比淀基 Η 1454 5,6-0CH20_ cf3 Ce〇3-峨淀基 Η 1455 5,6-0CH20- cf3 CX-4-外匕淀基 Η 1456 5,6-0CH20- cf3 C = C-2-呋喃基 Η 1457 5,6-0CH20- cf3 C Ξ C-3-咬喃基 Η 1458 5,6-0CH20- cf3 C Ξ C-2-p塞吩基 Η 1459 5,6_0CH20- cf3 OC-3-嘍吩基 Η 1460 5,6-0CH20- cf3 OC-2-嘮唑基 Η 1461 5,6-0CH20- cf3 C = C-2-嘍唑基 Η 1462 5,6-0CH20- cf3 C^C-4-異噚唑基 Η 1463 5,6-0CH20- cf3 C = C-2-咪唑基 Η -108 - (請先閱讀背面之注意事項再填寫本頁) 本紙張尺度適用中國國家標準(CNS ) A4規格(210X 297公釐) 587078 經濟部中央標準局員工消費合作社印製 kl B7 五、發明説明(1ί)6)1404 6-NH2 cf3 C ^ C-2-distenyl H 1405 6-NH2 cf3 C ^ C-3e Cephenyl H 1406 6-NMe2 cf3 C = C-cycPr H 1407 6-NMe2 cf3 C ^ C-Ph H 1408 6-NMe2 cf3 C Ξ C-2-p than Yodo-based H 1409 6-NMe2 cf3 Ce〇3_ Edo-based H 1410 6-NMe2 cf3 Ce〇4-p than Yodo-based H 1411 6-NMe2 cf3 C Ξ C_2 -Branyl H 1412 6-NMe2 cf3 C Ξ C-3-Branyl H 1413 6-NMe2 cf3 C ^ C-2-pyriminyl H 1414 6-NMe2 cf3 C Ξ C-3-p sephenyl H 1415 7-C1 cf3 C = C-cycPr H 1416 7-C1 cf3 C ^ C-Ph H 1417 7-C1 cf3 C = 02-ρ than HYD H 1418 7-C1 cf3 CeC-3-pyridyl H 1419 7-C1 cf3 C ξ C-4-Eodoyl H 1420 7-C1 cf3 C = C-2-pyranyl H 1421 7-C1 cf3 C Ξ C-3-pyranyl H 1422 7-C1 cf3 C = C-2-fluorenyl H 1423 7-C1 cf3 C Ξ C-3-ρ sephenyl H 1424 5,6-0CH20- cf3 C = C-cycPr H 1425 5,6-0CH20- cf3 C ^ CCH2CH2OH H 1426 5,6-0CH20- cf3 C ^ C-CH (OH) Me H 1427 5,6-0CH20- cf3 C ^ C-Ph H 1428 5,6-0CH20- cf3 C = C- (2-Cl) Ph H 1429 5,6_0CH20- cf3 C ^ C- (3-Cl) Ph H 1430 5,6-0CH20- cf3 C ^ C- (4-Cl) Ph H 1431 5,6_0CH20- cf3 C = C- (2 -F) Ph H 1432 5,6-0CH20- cf3 C ^ C- (3 -F) Ph H 1433 5,6-0CH20- cf3 C ^ C- (4-F) Ph H (Please read the notes on the back before filling out this page) -107- This paper size applies to Chinese National Standard (CNS) A4 specification (210X297mm) 587078 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 105 V. Description of the invention () 1434 5,6-0CH20- cf3 C ^ C- (2-OH) Ph Η 1435 5,6 -0CH20- cf3 C = C- (3-〇H) Ph Η 1436 5,6-0CH20- cf3 C ^ C- (4-OH) Ph Η 1437 5,6-0CH20- cf3 C ^ C- (2- OMe) Ph Η 1438 5,6-0CH20- cf3 C ^ C- (3-OMe) Ph Η 1439 5,6-0CH20- cf3 C = C- (4-OMe) Ph Η 1440 5,6-0CH20- cf3 C = C- (2-CN) Ph Η 1441 5,6-0CH20- cf3 C ^ C- (3-CN) Ph Η 1442 5,6-0CH20- cf3 C ^ C- (4-CN) Ph Η 1443 5,6-0CH20- cf3 C tri-C- (2-N02) Ph Η 1444 5,6-0CH20- cf3 C ^ C- (3-N02) Ph Η 1445 5,6-0CH20- cf3 〇C- (4 -N02) Ph Η 1446 5,6_0CH20 · cf3 C ^ C- (2-NH2) Ph Η 1447 5,6-0CH20- cf3 C ^ C- (3-NH2) Ph Η 1448 5,6-0CH20- cf3 C ^ C- (4-NH2) Ph Η 1449 5,6-0CH20- cf3 C ^ C- (2-NMe2) Ph Η 1450 5,6-0CH20- cf3 C three C- (3_NMe2) Ph Η 1451 5,6 -0CH20- cf3 C ^ C- (4-NMe2) Ph Η 1452 5,6-0CH20- cf3 CeC_2 · py Base Η 1453 5,6-0CH20- cf3 C Ξ C-2-p ratio Yodo base Η 1454 5,6-0CH20_ cf3 Ce〇3-Edian base Η 1455 5,6-0CH20- cf3 CX-4-outer dagger Yodo base Η 1456 5,6-0CH20- cf3 C = C-2-furanyl Η 1457 5,6-0CH20- cf3 C Ξ C-3-pyranyl Η 1458 5,6-0CH20- cf3 C Ξ C- 2-p sedenyl fluorene 1459 5,6_0CH20- cf3 OC-3-fluorenyl fluorene 1460 5,6-0CH20- cf3 OC-2-oxazolyl fluorene 1461 5,6-0CH20- cf3 C = C-2 -OxazolylΗ 1462 5,6-0CH20- cf3 C ^ C-4-isoxazolylΗ 1463 5,6-0CH20- cf3 C = C-2-imidazolylΗ -108-(Please read the Note: Please fill in this page again.) This paper size applies Chinese National Standard (CNS) A4 (210X 297 mm). 587078 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs.
1464 6-COCH3 cf3 C=C-cycPr H 1465 6-COCH3 cf3 C=C-Ph H 1466 6-COCH3 cf3 C=C-2-吡啶基 H 1467 6-COCH3 cf3 C=C-3_p比淀基 H 1468 6-COCH3 cf3 C=C-4-p比淀基 H 1469 6.COCH3 cf3 C=C-2-咬喃基 H 1470 6-COCH3 cf3 C=C-3-咬喃基 H 1471 6-COCH3 cf3 C=C-2-嘍吩基 H 1472 6-COCH3 cf3 OC-3-嘧吩基 H 1473 6-NH2 cf3 C=C-cycPr H 1474 6-NH2 cf3 C=C-Ph H 1475 6·ΝΗ2 cf3 C=C -2 _ p比咬基 H 1476 6_ΝΉ2 cf3 C=C-3-p》b淀基 H 1477 6-ΝΗ2 cf3 C=C-4-p比淀基 H 1478 6-ΝΗ2 cf3 C=C_2_呋喃基 H 1479 6·ΝΗ2 cf3 C=C-3-咬喃基 H 1480 6-ΝΗ2 cf3 C=C-2-p塞吩基 H 1481 6_ΝΗ2 cf3 C=C-3-p塞吩基 H 1482 6-NMe2 cf3 C=C-cycPr H 1483 6-NMe2 cf3 OC-Ph H 1484 6-NMe2 cf3 C=C-2-吡啶基 H 1485 6-NMe2 cf3 OC_3-吡啶基 H 1486 6-NMe2 cf3 C=C-4-#b 淀基 H 1487 6-NMe2 cf3 C=C-2-咬喃基 H 1488 6-NMe2 cf3 C=C-3-咬喃基 H 1489 6-NMe2 cf3 C=C-2-p塞吩基 H 1490 6-NMe2 cf3 C=C-3-嘍吩基 H 1491 7-C1 cf3 C=C-cycPr H 1492 7-C1 cf3 C=C_Ph H 1493 7-C1 cf3 C=C-2-p比淀基 H (請先閱讀背面之注意事項再填寫本頁) -109- 本紙張尺度適用中國國家標準(CNS ) Α4規格(210Χ 297公釐) 587078 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明(1Q7)1464 6-COCH3 cf3 C = C-cycPr H 1465 6-COCH3 cf3 C = C-Ph H 1466 6-COCH3 cf3 C = C-2-pyridyl H 1467 6-COCH3 cf3 C = C-3_p 1468 6-COCH3 cf3 C = C-4-p than Yodo H 1469 6.COCH3 cf3 C = C-2-Oranyl H 1470 6-COCH3 cf3 C = C-3-Oranyl H 1471 6-COCH3 cf3 C = C-2-fluorenyl H 1472 6-COCH3 cf3 OC-3-pyridinyl H 1473 6-NH2 cf3 C = C-cycPr H 1474 6-NH2 cf3 C = C-Ph H 1475 6 · ΝΗ2 cf3 C = C -2 _ p ratio H 1476 6_NΉ2 cf3 C = C-3-p》 bYodo H 1477 6-ΝΗ2 cf3 C = C-4-p ratio Y H 1478 6-ΝΗ2 cf3 C = C_2_furanyl H 1479 6 · NΗ2 cf3 C = C-3-branyl H 1480 6-ΝΗ2 cf3 C = C-2-p sedenyl H 1481 6_ΝΗ2 cf3 C = C-3-p sedenyl H 1482 6-NMe2 cf3 C = C-cycPr H 1483 6-NMe2 cf3 OC-Ph H 1484 6-NMe2 cf3 C = C-2-pyridyl H 1485 6-NMe2 cf3 OC_3-pyridyl H 1486 6-NMe2 cf3 C = C-4- # b Yodo-based H 1487 6-NMe2 cf3 C = C-2-Oranyl H 1488 6-NMe2 cf3 C = C-3-Oranyl H 1489 6-NMe2 cf3 C = C-2 -p sephenyl H 1490 6-NMe2 cf3 C = C-3-fluorenyl H 1491 7-C1 cf3 C = C-cycPr H 1492 7-C1 cf3 C = C_Ph H 1493 7-C1 cf3 C = C- 2-p ratio Dianji H (Please read the notes on the back before filling in this page) -109- This paper size is applicable to China National Standard (CNS) A4 specifications (210 × 297 mm) 587078 Printed by A7, B7, Consumer Cooperatives V. Description of the invention (1Q7)
1494 7-C1 cf3 C=C-3-flt 咬基 H 1495 7-C1 cf3 C=C-4_p比淀基 H 1496 7-C1 cf3 C=C-2-咬喃基 H 1497 7-C1 cf3 C=C_3-呋喃基 H 1498 7-C1 cf3 C=C-2-p塞吩基 H 1499 7-C1 cf3 C=C-3-p塞吩基 H 1500 5,6-0CH20- cf3 C=C-cycPr H 1501 5,6-0CH20- cf3 C=CCH2CH2OH H 1502 5,6-0CH20- cf3 C=C-CH(OH)Me H 1503 5,6-0CH20- cf3 OC-Ph H 1504 5,6-0CH20- cf3 C=C-(2-Cl)Ph H 1505 5,6-0CH20- cf3 C=C-(3-Cl)Ph H 1506 5,6-0CH20- cf3 C=C-(4-Cl)Ph H 1507 5,6-0CH20- cf3 C=C-(2_F)Ph H 1508 5,6-0CH20· cf3 C=C-(3-F)Ph H 1509 5,6-0CH20- cf3 C=C-(4-F)Ph H 1510 5,6-0CH20- cf3 C=C-(2-0H)Ph H 1511 5,6-0CH20- cf3 C=C-(3-0H)Ph H 1512 5,6-0CH20- cf3 C=C-(4-0H)Ph H 1513 5,6_0CH20· cf3 C=C_(2-0Me)Ph H 1514 5,6-0CH20- cf3 C=C-(3-0Me)Ph H 1515 5,6-0CH20_ cf3 C=C-(4-0Me)Ph H 1516 5,6-0CH20· cf3 C=C-(2-CN)Ph H 1517 5,6-0CH20- cf3 C=C-(3-CN)Ph H 1518 5,6-0CH20' cf3 C=C-(4-CN)Ph H 1519 5,6-0CH20- cf3 C=C-(2-N02)Ph H 1520 5,6-0CH20- cf3 C=C-(3-N02)Ph H 1521 5,6-0CH20- cf3 C=C_(4-N02)Ph H 1522 5,6-0CH20- cf3 C=C-(2-NH2)Ph H 1523 5,6-0CH20- cf3 C=C-(3-NH2)Ph H -110- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X 297公釐) 587078 經濟部中央標準局員工消費合作社印製 A7 B71494 7-C1 cf3 C = C-3-flt octyl H 1495 7-C1 cf3 C = C-4_p ratio HYD 1496 7-C1 cf3 C = C-2-octyl H 1497 7-C1 cf3 C = C_3-furanyl H 1498 7-C1 cf3 C = C-2-p sedenyl H 1499 7-C1 cf3 C = C-3-p sedenyl H 1500 5,6-0CH20- cf3 C = C- cycPr H 1501 5,6-0CH20- cf3 C = CCH2CH2OH H 1502 5,6-0CH20- cf3 C = C-CH (OH) Me H 1503 5,6-0CH20- cf3 OC-Ph H 1504 5,6-0CH20 -cf3 C = C- (2-Cl) Ph H 1505 5,6-0CH20- cf3 C = C- (3-Cl) Ph H 1506 5,6-0CH20- cf3 C = C- (4-Cl) Ph H 1507 5,6-0CH20- cf3 C = C- (2_F) Ph H 1508 5,6-0CH20 · cf3 C = C- (3-F) Ph H 1509 5,6-0CH20- cf3 C = C- ( 4-F) Ph H 1510 5,6-0CH20- cf3 C = C- (2-0H) Ph H 1511 5,6-0CH20- cf3 C = C- (3-0H) Ph H 1512 5,6-0CH20 -cf3 C = C- (4-0H) Ph H 1513 5,6_0CH20 · cf3 C = C_ (2-0Me) Ph H 1514 5,6-0CH20- cf3 C = C- (3-0Me) Ph H 1515 5 , 6-0CH20_ cf3 C = C- (4-0Me) Ph H 1516 5,6-0CH20 · cf3 C = C- (2-CN) Ph H 1517 5,6-0CH20- cf3 C = C- (3- CN) Ph H 1518 5,6-0CH20 'cf3 C = C- (4-CN) Ph H 1519 5,6-0CH20- cf3 C = C- (2-N02) Ph H 1520 5,6-0CH20- cf3 C = C- (3-N02) Ph H 1521 5,6-0CH20- cf3 C = C_ (4-N02) Ph H 1522 5,6-0C H20- cf3 C = C- (2-NH2) Ph H 1523 5,6-0CH20- cf3 C = C- (3-NH2) Ph H -110- This paper size applies to China National Standard (CNS) A4 specification (210X 297 mm) 587078 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7
Λ QO 五、發明説明()Λ QO V. Description of the invention ()
1524 5,6-0CH20- cf3 C=C-(4-NH2)Ph H 1525 5,6-0CH20_ cf3 C=C-(2-NMe2)Ph H 1526 5,6-0CH20· cf3 C=C-(3-NMe2)Ph H 1527 5,6-0CH20 - cf3 C=C-(4-NMe2)Ph H 1528 5,6-0CH20- cf3 C=C-2-p比咬基 H 1529 5,6-0CH20- cf3 淀基 H 1530 5,6-0CH20- cf3 基 H 1531 5,6-0CH20- cf3 C=C-4-吡啶基 H 1532 5,6-0CH20- cf3 C=C-2-呋喃基 H 1533 5,6_0CH20_ cf3 C=C-3-咬喃基 H 1534 5,6-0CH20- cf3 C=C-2-p塞吩基 H 1535 5,6-0CH20- cf3 〇C-3-嘍吩基 H 1536 5,6_0CH20- cf3 OC-2-嘮唑基 H 1537 5,6-0CH20- cf3 C=C-2-^ 峻基 H 1538 5,6-0CH20- cf3 OC-4-異吟坐基 H 1539 5,6-0CH20- cf3 C=C-2-咪唑基 H 1540 5,6-0CH20- cf3 CH2CH2-cycPr H 1541 5,6-0CH20- cf3 CH2CH2CH2CH2OH H 1542 5,6-0CH20- cf3 CH2CH2-CH(OH)Me H 1543 5,6-0CH20- cf3 CH2CH2-Ph H 1544 5,6-0CH20- cf3 CH2CHr(2-Cl)Ph H 1545 5,6-0CH20- cf3 CH2CH2-(3-Cl)Ph H 1546 5,6-0CH20- cf3 CH2CHr(4-Cl)Ph H 1547 5,6-0CH20· cf3 CH2CH2-(2-F)Ph H 1548 5,6-0CH20- cf3 CH2CH2-(3-F)Ph H 1549 5,6-0CH20- cf3 CH2CH2-(4-F)Ph H 1550 5,6-0CH20- cf3 CH2CHr(2_OH)Ph H 1551 5,6-0CH20- cf3 CH2CHr(3-OH)Ph H 1552 5,6-0CH20- cf3 CH2CH2-(4-OH)Ph H 1553 5,6-0CH20 - cf3 CH2CH2-(2-OMe)Ph H -111 - (請先閱讀背面之注意事項再填寫本頁) 、1Τ .__ 本紙張尺度適用中國國家標準(CNS ) A4規格(210X 297公釐) 587078 經濟部中央標準局員工消費合作社印製 A7 B7 109 五、發明説明() 1554 5,6_0CH20- cf3 CH2CH2-(3-OMe)Ph Η 1555 5,6_0CH20- cf3 CH2CH2-(4-OMe)Ph Η 1556 5,6-0CH20· cf3 CH2CH2-(2_CN)Ph Η 1557 5,6-0CH20- cf3 CH2CH2_(3-CN)Ph Η 1558 5,6-0CH20- cf3 CH2CH2-(4-CN)Ph Η 1559 5,6-0CH20- cf3 CH2CHr(2-N02)Ph Η 1560 5,6-0CH2O cf3 CH2CH2-(3-N02)Ph Η 1561 5,6-0CH20- cf3 CH2CH2-(4-N02)Ph Η 1562 5,6-0CH20- cf3 CH2CH2-(2-NH2)Ph Η 1563 5,6-0CH20- cf3 CH2CH2-(3-NH2)Ph Η 1564 5,6-0CH20- cf3 CH2CH2-(4-NH2)Ph Η 1565 5,6-0CH20- cf3 CH2CH2-(2-NMe2)Ph Η 1566 5,6-0CH20- cf3 CH2CHr(3_NMe2)Ph Η 1567 5,6-0CH20- cf3 CH2CH2-(4-NMe2)Ph Η 1568 5,6-0CH20- cf3 CH2CH2-2-吡啶基 Η 1569 5,6-0CH20- cf3 CH2CH2-3·吡啶基 Η 1570 5,6-0CH20- cf3 CH2CH2-4-吡啶基 Η 1571 5,6-0CH20- cf3 CH2CH2_2_呋喃基 Η 1572 5,6-0CH20_ cf3 CH2CH2-3-呋喃基 Η 1573 5,6-0CH20- cf3 CH2CHr2-嘧吩基 Η 1574 5,6-0CH20- cf3 CH2CHr3-噻吩基 Η 1575 5,6-0CH20- cf3 CH2CH2-2-嘮唑基 Η 1576 5,6-0CH20- cf3 CH2CHr2-嘧唑基 Η 1577 5,6-0CH20- cf3 CH2CH2-4-異崎唑基 Η 1578 5,6-0CH20- cf3 CH2CH2-2-咪唑基 Η 1579 5,6-0CH20- cf3 C Ξ C-cycPr ch3 1580 5,6-0CH20- cf3 OC-Ph ch3 1581 5,6-0CH20- cf3 C三C-2· 口比淀基 ch3 1582 5,6_0CH20- cf3 C三C-3-口比淀基 ch3 1583 5,6-0CH20- cf3 C = C-4-吡啶基 ch3 (請先閲讀背面之注意事項再填寫本頁) 112- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X 297公釐) 587078 經濟部中央標準局員工消費合作社印製 A7 B7 110 五、發明説明() 1584 5,6-0CH20· cf3 C = C-2-咬喃基 ch3 1585 5,6-0CH20_ cf3 C = C-3-咬喃基 ch3 1586 5,6-0CH20- cf3 C^C_2-嘧吩基 ch3 1587 5,6_0CH20- cf3 C Ξ C-3·*7塞吩基 ch3 1588 5,6-0CH20- cf3 C=C-cycPr ch3 1589 5,6-0CH20· cf3 OC-Ph ch3 1590 5,6-0CH20- cf3 C=C-2·吡啶基 ch3 1591 5,6-0CH20- cf3 C=C-3 比淀基 ch3 1592 5,6-0CH20· cf3 C=C-4-p比淀基 ch3 1593 5,6-OCH20- cf3 C=C_2_呋喃基 ch3 1594 5,6-0CH20- cf3 C=C-3-咬喃基 ch3 1595 5,6-0CH20· cf3 C=C-2-嘍吩基 ch3 1596 5,6-0CH20- cf3 C=C-3·嘧吩基 ch3 1597 5,6-0CH2O cf3 CH2CH2-cycPr ch3 1598 5,6-0CH20- cf3 CH2CH2-Ph ch3 1599 5,6-0CH20· cf3 CH2CHr2-吡啶基 ch3 1600 5,6-0CH20- cf3 CH2CH2-3-吡啶基 ch3 1601 5,6-0CH20- cf3 CH2CH2-4_吡啶基 ch3 1602 5,6-0CH20- cf3 CH2CH2-2-呋喃基 ch3 1603 5,6-0CH20- cf3 CH2CHr3-呋喃基 ch3 1604 5,6-0CH20· cf3 CH2CHr2-嘧吩基 ch3 1605 5,6-0CH20- cf3 CH2CHr3-嘍吩基 ch3 1606 5,6-0CH20- cf3 C = C-cycPr CH2CH3 1607 5,6-0CH20- cf3 C = C-Ph CH2CH3 1608 5,6-0CH20- cf3 C三C_2-口比淀基 CH2CH3 1609 5,6-0CH20- cf3 C = C_3-p比淀基 CH2CH3 1610 5,6-0CH20- cf3 CeC-4-吡啶基 CH2CH3 1611 5,6-0CH20- cf3 C = C-2-呋喃基 ch2ch3 1612 5,6-0CH20- cf3 C Ξ C-3-咬喃基 ch2ch3 1613 5,6-0CH20- cf3 C = C-2-遠吩基 CH2CH3 (請先閱讀背面之注意事項再填寫本頁) -113- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 587078 經濟部中央標準局員工消費合作社印製 A7 B7 111 五、發明説明() 1614 5,6-0CH20- cf3 C Ξ C-3-p塞吩基 CH2CH3 1615 5,6-0CH20- cf3 C=C-cycPr ch2ch3 1616 5,6-0CH20- cf3 C=C-Ph ch2ch3 1617 5,6-0CH20- cf3 C=C-2-p比淀基 ch2ch3 1618 5,6-0CH20· cf3 C=C-3-吡啶基 CH2CH3 1619 5,6-0CH20- cf3 ,C=C-4·吡啶基 CH2CH3 1620 5,6-0CH20- cf3 C=C-2-呋喃基 CH2CH3 1621 5,6-0CH20- cf3 C=C-3-呋喃基 CH2CH3 1622 5,6-0CH20- cf3 C=C-2-嘍吩基 CH2CH3 1623 5,6_OCH20- cf3 C=C_3-嘧吩基 ch2ch3 1624 5,6-0CH2O cf3 CH2CH2-cycPr CH2CH3 1625 5,6-OCH^O- cf3 CH2CH2-Ph CH2CH3 1626 5,6-0CH20- cf3 CH2CHr2-吡啶基 CH2CH3 1627 5,6-0CH20- cf3 CH2CHr3-吡啶基 CH2CH3 1628 5,6-0CH20- cf3 CH2CH2-4-吡啶基 CH2CH3 1629 5,6-0CH20- cf3 CH2CHr2_呋喃基 CH2CH3 1630 5,6-0CH20- cf3 CH2CH2-3_呋喃基 CH2CH3 1631 5,6-0CH20- cf3 CH2CHr2-嘧吩基 CH2CH3 1632 5,6-0CH20· cf3 CH2CH2-3_嘧吩基 CH2CH3 *除非特別提及,否則立體化學性是(+/-)。 -114- (請先閱讀背面之注意事項再填寫本頁)1524 5,6-0CH20- cf3 C = C- (4-NH2) Ph H 1525 5,6-0CH20_ cf3 C = C- (2-NMe2) Ph H 1526 5,6-0CH20 · cf3 C = C- ( 3-NMe2) Ph H 1527 5,6-0CH20-cf3 C = C- (4-NMe2) Ph H 1528 5,6-0CH20- cf3 C = C-2-p ratio H 1529 5,6-0CH20 -cf3 yl H 1530 5,6-0CH20- cf3 yl H 1531 5,6-0CH20- cf3 C = C-4-pyridylH 1532 5,6-0CH20- cf3 C = C-2-furyl H 1533 5,6_0CH20_ cf3 C = C-3-octanoyl H 1534 5,6-0CH20- cf3 C = C-2-p sedenyl H 1535 5,6-0CH20- cf3 〇C-3-fluorenyl H 1536 5,6_0CH20- cf3 OC-2-oxazolyl H 1537 5,6-0CH20- cf3 C = C-2- ^ Junki H 1538 5,6-0CH20- cf3 OC-4-isosinyl H 1539 5,6-0CH20- cf3 C = C-2-imidazolyl H 1540 5,6-0CH20- cf3 CH2CH2-cycPr H 1541 5,6-0CH20- cf3 CH2CH2CH2CH2OH H 1542 5,6-0CH20- cf3 CH2CH2-CH ( OH) Me H 1543 5,6-0CH20- cf3 CH2CH2-Ph H 1544 5,6-0CH20- cf3 CH2CHr (2-Cl) Ph H 1545 5,6-0CH20- cf3 CH2CH2- (3-Cl) Ph H 1546 5,6-0CH20- cf3 CH2CHr (4-Cl) Ph H 1547 5,6-0CH20 · cf3 CH2CH2- (2-F) Ph H 1548 5,6-0CH20- cf3 CH2CH2- (3-F) Ph H 1549 5,6-0CH20- cf3 CH2CH2- (4-F) Ph H 1550 5,6-0CH20- cf3 C H2CHr (2_OH) Ph H 1551 5,6-0CH20- cf3 CH2CHr (3-OH) Ph H 1552 5,6-0CH20- cf3 CH2CH2- (4-OH) Ph H 1553 5,6-0CH20-cf3 CH2CH2- ( 2-OMe) Ph H -111-(Please read the notes on the back before filling out this page), 1T .__ This paper size applies to China National Standard (CNS) A4 (210X 297 mm) 587078 Central Bureau of Standards, Ministry of Economic Affairs Printed by employee consumer cooperative A7 B7 109 V. Description of invention () 1554 5,6_0CH20- cf3 CH2CH2- (3-OMe) Ph Η 1555 5,6_0CH20- cf3 CH2CH2- (4-OMe) Ph Η 1556 5,6-0CH20 Cf3 CH2CH2- (2_CN) Ph Η 1557 5,6-0CH20- cf3 CH2CH2_ (3-CN) Ph Η 1558 5,6-0CH20- cf3 CH2CH2- (4-CN) Ph Η 1559 5,6-0CH20- cf3 CH2CHr (2-N02) Ph Η 1560 5,6-0CH2O cf3 CH2CH2- (3-N02) Ph Η 1561 5,6-0CH20- cf3 CH2CH2- (4-N02) Ph Η 1562 5,6-0CH20- cf3 CH2CH2 -(2-NH2) Ph Η 1563 5,6-0CH20- cf3 CH2CH2- (3-NH2) Ph Η 1564 5,6-0CH20- cf3 CH2CH2- (4-NH2) Ph Η 1565 5,6-0CH20- cf3 CH2CH2- (2-NMe2) Ph Η 1566 5,6-0CH20- cf3 CH2CHr (3_NMe2) Ph Η 1567 5,6-0CH20- cf3 CH2CH2- (4-NMe2) Ph Η 1568 5,6-0CH20- cf3 CH2CH2- 2-pyridylfluorene 1569 5,6-0C H20- cf3 CH2CH2-3 · pyridylfluorene 1570 5,6-0CH20- cf3 CH2CH2-4-pyridylfluorene 1571 5,6-0CH20- cf3 CH2CH2_2_furanylfluorene 1572 5,6-0CH20_ cf3 CH2CH2-3-furan Base Η 1573 5,6-0CH20- cf3 CH2CHr2-pyridinyl Η 1574 5,6-0CH20- cf3 CH2CHr3-ThienylΗ 1575 5,6-0CH20- cf3 CH2CH2-2-oxazolyl 576 1576 5,6- 0CH20- cf3 CH2CHr2-pyrazolyl fluorene 1577 5,6-0CH20- cf3 CH2CH2-4-isoazazolyl fluorene 1578 5,6-0CH20- cf3 CH2CH2-2-imidazolyl fluorene 1579 5,6-0CH20- cf3 C Ξ C-cycPr ch3 1580 5,6-0CH20- cf3 OC-Ph ch3 1581 5,6-0CH20- cf3 C three C-2 · mouth ratio Yodo ch3 1582 5,6_0CH20- cf3 C three C-3- mouth ratio Yodo ch3 1583 5,6-0CH20- cf3 C = C-4-pyridyl ch3 (Please read the precautions on the back before filling out this page) 112- This paper size applies to China National Standard (CNS) A4 specifications (210X 297 (Mm) 587078 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 110 V. Description of the invention () 1584 5,6-0CH20 · cf3 C = C-2-Branyl ch3 1585 5,6-0CH20_ cf3 C = C-3-branyl ch3 1586 5,6-0CH20- cf3 C ^ C_2-pyriminyl ch3 1587 5,6_0CH20- cf3 C Ξ C-3 · * 7 Sedenyl ch3 1588 5,6-0CH20- cf3 C = C-cycPr ch3 1589 5,6-0CH20 · cf3 OC-Ph ch3 1590 5,6-0CH20- cf3 C = C- 2 · pyridyl ch3 1591 5,6-0CH20- cf3 C = C-3 than yodo ch3 1592 5,6-0CH20 · cf3 C = C-4-p than yodo ch3 1593 5,6-OCH20- cf3 C = C_2_furanyl ch3 1594 5,6-0CH20- cf3 C = C-3-branyl ch3 1595 5,6-0CH20 · cf3 C = C-2-fluorenyl ch3 1596 5,6-0CH20- cf3 C = C-3 · pyrimyl ch3 1597 5,6-0CH2O cf3 CH2CH2-cycPr ch3 1598 5,6-0CH20- cf3 CH2CH2-Ph ch3 1599 5,6-0CH20 · cf3 CH2CHr2-pyridyl ch3 1600 5,6 -0CH20- cf3 CH2CH2-3-pyridyl ch3 1601 5,6-0CH20- cf3 CH2CH2-4_pyridyl ch3 1602 5,6-0CH20- cf3 CH2CH2-2-furyl ch3 1603 5,6-0CH20- cf3 CH2CHr3 -Furyl ch3 1604 5,6-0CH20 · cf3 CH2CHr2-pyrimyl ch3 1605 5,6-0CH20- cf3 CH2CHr3-fluorenyl ch3 1606 5,6-0CH20- cf3 C = C-cycPr CH2CH3 1607 5,6 -0CH20- cf3 C = C-Ph CH2CH3 1608 5,6-0CH20- cf3 C three C_2-port ratio CH2CH3 1609 5,6-0CH20- cf3 C = C_3-p ratio ridge CH2CH3 1610 5,6-0CH20 -cf3 CeC-4-pyridylCH2CH3 1611 5,6-0CH20- cf3 C = C-2-furyl ch2ch3 1612 5,6-0CH20- cf3 C Ξ C-3-branyl ch2ch3 1613 5,6-0CH20- cf3 C = C-2-farphenyl CH2CH3 (Please read the back first Please note this page before filling out this page) -113- This paper size is applicable to Chinese National Standard (CNS) A4 (210X297 mm) 587078 Printed by A7 B7 111, Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of invention () 1614 5 , 6-0CH20- cf3 C Ξ C-3-p sephenyl CH2CH3 1615 5,6-0CH20- cf3 C = C-cycPr ch2ch3 1616 5,6-0CH20- cf3 C = C-Ph ch2ch3 1617 5,6- 0CH20- cf3 C = C-2-p than Yodo ch2ch3 1618 5,6-0CH20 · cf3 C = C-3-pyridyl CH2CH3 1619 5,6-0CH20- cf3, C = C-4 · pyridyl CH2CH3 1620 5,6-0CH20- cf3 C = C-2-furyl CH2CH3 1621 5,6-0CH20- cf3 C = C-3-furyl CH2CH3 1622 5,6-0CH20- cf3 C = C-2-fluorenyl CH2CH3 1623 5,6_OCH20- cf3 C = C_3-pyrimyl ch2ch3 1624 5,6-0CH2O cf3 CH2CH2-cycPr CH2CH3 1625 5,6-OCH ^ O- cf3 CH2CH2-Ph CH2CH3 1626 5,6-0CH20- cf3 CH2CHr2- Pyridyl CH2CH3 1627 5,6-0CH20- cf3 CH2CHr3-pyridyl CH2CH3 1628 5,6-0CH20- cf3 CH2CH2-4-pyridyl CH2CH3 16 29 5,6-0CH20- cf3 CH2CHr2_furanylCH2CH3 1630 5,6-0CH20- cf3 CH2CH2-3_furanyl CH2CH3 1631 5,6-0CH20- cf3 CH2CHr2-pyrimidyl CH2CH3 1632 5,6-0CH20 · cf3 CH2CH2-3_pyriminylCH2CH3 * Unless specifically mentioned, the stereochemistry is (+/-). -114- (Please read the notes on the back before filling this page)
、1T __ 本紙張尺度適用中國國家標準(CNS ) Α4規格(210X 297公釐) 587078 - A7 B7 112 五、發明説明() 表3 *、 1T __ This paper size is applicable to China National Standard (CNS) A4 specification (210X 297mm) 587078-A7 B7 112 V. Description of invention () Table 3 *
經濟部中央標準局員工消費合作社印製 範例# R3 R1 R2 R8、 1 6-C1 cf3 C = C-Pr H 2 6-C1 cf3 C^C-Bu H 3 6_C1 cf3 C^C-iBu H 4 6-C1 cf3 C Ξ C-tBu H 5 6-C1 cf3 K-Me H 6 6-C1 cf3 CH2CH2CH2CH2CH3 H 7 6-C1 cf3 CH2CH2CH(CH3)2 H 8 6-C1 cf3 CH2CH2CH2CH3 H 9 6-C1 cf3 CH2CH2CH3 H 10 6-C1 cf3 CH2CH2-tBu H 11 6-C1 cf3 CH2C^C-CH3 H 12 6·α cf3 ch2c^c-ch2ch3 H 13 6·α cf3 C^C-iPr ch3 14 6-α cf3 C = C-Pr ch3 15 6·α cf3 C^C-Bu ch3 16 6-α cf3 C^C-iBu ch3 17 6-C1 cf3 C-tBu ch3 18 6_α cf3 C^C-Et ch3 19 6-α cf3 C^C-Me ch3 20 6-α cf3 CH2C = C_CH3 ch3 21 6-α cf3 ch2c^c-ch2ch3 ch3 22 6-α cf3 CH2CH2CH(CH3)2 ch3 23 6-α cf3 ch2ch2ch2ch3 ch3 24 6-α cf3 ch2ch2ch3 ch3 ---— |_^---0------1T------#--, f m (請先閱讀背面之注意事項再填寫本頁) 、 -115- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X 297公釐) 587078 經濟部中央標準局員工消費合作社印製 B7 — 一 五、發明説明() 25 6-C1 cf3 CH2CH2-tBu 26 6_C1 cf3 C = C_iPr 27 6-C1 cf3 C^C-Pr 28 6_C1 cf3 C^C-Bu 29 6-C1 cf3 C^C-iBu 30 6_C1 cf3 C^C-tBu 31 6-C1 cf3 C^C-Et 32 6_C1 cf3 C^C-Me 33 6_C1 cf3 CH2C«H3 34 6-C1 cf3 ch2c«h2ch3 35 6-C1 cf3 ch2ch2ch(ch3)2 36 6-C1 cf3 ch2ch2ch2ch3 37 6-C1 cf3 ch2ch2ch3 38 6-C1 cf3 CH2CHrtBu 39 6-MeO cf3 C = C-Pr 40 6-MeO cf3 C^C-Bu 41 6-MeO cf3 C^C-iBu 42 6-MeO cf3 C^C-tBu 43 6-MeO cf3 C^C-Et 44 6-MeO cf3 C = C_Me 45 6_MeO cf3 CH2C«H3 46 6-MeO cf3 ch2c^c-ch2ch3 47 6-MeO cf3 ch2ch2ch2ch2ch3 48 6-MeO cf3 ch2ch2ch(ch3)2 49 6-MeO cf3 CH2CH2CH2CH3 50 6-MeO cf3 ch2ch2ch3 51 6-MeO cf3 CH2CH2-tBu 52 6-MeO cf3 CH2C^C-CH3 53 6-MeO cf3 ch2c«h2ch3 54 6-MeO cf3 C^C-iPr 55 6-MeO cf3 C^C-Pr 56 6-MeO cf3 C^C-BuPrinted by the Consumer Standards Cooperative of the Central Bureau of Standards, Ministry of Economic Affairs # R3 R1 R2 R8, 1 6-C1 cf3 C = C-Pr H 2 6-C1 cf3 C ^ C-Bu H 3 6_C1 cf3 C ^ C-iBu H 4 6 -C1 cf3 C Ξ C-tBu H 5 6-C1 cf3 K-Me H 6 6-C1 cf3 CH2CH2CH2CH2CH3 H 7 6-C1 cf3 CH2CH2CH (CH3) 2 H 8 6-C1 cf3 CH2CH2CH2CH3 H 9 6-C1 cf3 CH2CH2CH3 H 10 6-C1 cf3 CH2CH2-tBu H 11 6-C1 cf3 CH2C ^ C-CH3 H 12 6 · α cf3 ch2c ^ c-ch2ch3 H 13 6 · α cf3 C ^ C-iPr ch3 14 6-α cf3 C = C -Pr ch3 15 6 · α cf3 C ^ C-Bu ch3 16 6-α cf3 C ^ C-iBu ch3 17 6-C1 cf3 C-tBu ch3 18 6_α cf3 C ^ C-Et ch3 19 6-α cf3 C ^ C-Me ch3 20 6-α cf3 CH2C = C_CH3 ch3 21 6-α cf3 ch2c ^ c-ch2ch3 ch3 22 6-α cf3 CH2CH2CH (CH3) 2 ch3 23 6-α cf3 ch2ch2ch2ch3 ch3 24 6-α cf3 ch2ch2 --- | _ ^ --- 0 ------ 1T ------ #-, fm (Please read the notes on the back before filling this page), -115- This paper size is applicable to China National Standard (CNS) A4 specification (210X 297 mm) 587078 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs B7 — One, five, invention description () 25 6-C1 cf3 CH2CH2-tBu 26 6_C 1 cf3 C = C_iPr 27 6-C1 cf3 C ^ C-Pr 28 6_C1 cf3 C ^ C-Bu 29 6-C1 cf3 C ^ C-iBu 30 6_C1 cf3 C ^ C-tBu 31 6-C1 cf3 C ^ C- Et 32 6_C1 cf3 C ^ C-Me 33 6_C1 cf3 CH2C «H3 34 6-C1 cf3 ch2c« h2ch3 35 6-C1 cf3 ch2ch2ch (ch3) 2 36 6-C1 cf3 ch2ch2ch2ch3 37 6-C1 cf3 ch2ch2ch2ch2ch2ch3ch CH2CHrtBu 39 6-MeO cf3 C = C-Pr 40 6-MeO cf3 C ^ C-Bu 41 6-MeO cf3 C ^ C-iBu 42 6-MeO cf3 C ^ C-tBu 43 6-MeO cf3 C ^ C- Et 44 6-MeO cf3 C = C_Me 45 6_MeO cf3 CH2C «H3 46 6-MeO cf3 ch2c ^ c-ch2ch3 47 6-MeO cf3 ch2ch2ch2ch2ch3 48 6-MeO cf3 ch2ch2ch (ch3) 2 49 6-MeO cf3 CH2 CH2 MeO cf3 ch2ch2ch3 51 6-MeO cf3 CH2CH2-tBu 52 6-MeO cf3 CH2C ^ C-CH3 53 6-MeO cf3 ch2c «h2ch3 54 6-MeO cf3 C ^ C-iPr 55 6-MeO cf3 C ^ C-Pr 56 6-MeO cf3 C ^ C-Bu
ch3 ch2ch3 ch2ch3 ch2ch3 CH2CH3 CH2CH3 ch2ch3 ch2ch3 CH2CH3 CH2CH3 ch2ch3 ch2ch3 CH2CH3 CH2CH3 H H H H (請先閱讀背面之注意事項再填寫本頁) -116- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 587078 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明(114)ch3 ch2ch3 ch2ch3 ch2ch3 CH2CH3 CH2CH3 ch2ch3 ch2ch3 CH2CH3 CH2CH3 ch2ch3 ch2ch3 CH2CH3 CH2CH3 HHHH (Please read the notes on the back before filling out this page) -116- This paper size is applicable to the Chinese national standard (CNS) 597X 297 (Aug. 208) 208 mm Printed by the Consumer Standards Cooperative of the Ministry of Standards of the People's Republic of China A7 B7 V. Invention Description (114)
57 6-MeO cf3 C^C-iBu ch3 58 6-MeO cf3 C = C-tBu ch3 59 6-MeO cf3 C^C-Et ch3 60 6-MeO cf3 C^C-Me ch3 61 6-MeO cf3 CH2C = C-CH3 ch3 62 6-MeO cf3 ch2c«h2ch3 ch3 63 6-MeO cf3 ch2ch2ch(ch3)2 ch3 64 6_MeO cf3 ch2ch2ch2ch3 ch3 65 6-MeO cf3 CH2CH2CH3 ch3 66 6-MeO cf3 CH2CHrtBu ch3 67 6-MeO cf3 C = C-iPr ch2ch3 68 6_MeO cf3 C^C-Pr CH2CH3 69 6-MeO cf3 C^C-Bu CH2CH3 70 6-MeO cf3 C^C-iBu CH2CH3 71 6-MeO cf3 C = C-tBu CH2CH3 72 6-MeO cf3 C^C-Et ch2ch3 73 6-MeO cf3 C^C-Me CH2CH3 74 6-MeO cf3 CH2C^C-CH3 CH2CH3 75 6-MeO cf3 ch2c^c-ch2ch3 CH2CH3 76 6-MeO cf3 ch2ch2ch(ch3)2 CH2CH3 77 6-MeO cf3 ch2ch2ch2ch3 ch2ch3 78 6-MeO cf3 ch2ch2ch3 ch2ch3 79 6-MeO cf3 CH2CH2-tBu ch2ch3 80 5,6-diF cf3 C^C-Pr H 81 5,6-diF cf3 C = C-Bu H 82 5,6_diF cf3 C^C-iBu H 83 5,6-diF cf3 C = C-tBu H 84 5,6-diF cf3 C = C-Me H 85 5,6-diF cf3 CH2C«H3 H 86 5,6-diF cf3 ch2c^c-ch2ch3 H 87 5,6-diF cf3 CH2CH2CH2CH2CH3 H 88 5,6-diF cf3 CH2CH2CH3 H (請先閱讀背面之注意事項再填寫本頁) -117- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 587078 經濟部中央標準局員工消費合作社印製 Μ Β7 五、發明説明(115)57 6-MeO cf3 C ^ C-iBu ch3 58 6-MeO cf3 C = C-tBu ch3 59 6-MeO cf3 C ^ C-Et ch3 60 6-MeO cf3 C ^ C-Me ch3 61 6-MeO cf3 CH2C = C-CH3 ch3 62 6-MeO cf3 ch2c «h2ch3 ch3 63 6-MeO cf3 ch2ch2ch (ch3) 2 ch3 64 6_MeO cf3 ch2ch2ch2ch3 ch3 65 6-MeO cf3 CH2CH2CH3 ch3 66 6-MeO cf3 cf3 ch3 = C-iPr ch2ch3 68 6_MeO cf3 C ^ C-Pr CH2CH3 69 6-MeO cf3 C ^ C-Bu CH2CH3 70 6-MeO cf3 C ^ C-iBu CH2CH3 71 6-MeO cf3 C = C-tBu CH2CH3 72 6- MeO cf3 C ^ C-Et ch2ch3 73 6-MeO cf3 C ^ C-Me CH2CH3 74 6-MeO cf3 CH2C ^ C-CH3 CH2CH3 75 6-MeO cf3 ch2c ^ c-ch2ch3 CH2CH3 76 6-MeO cf3 ch2ch2ch (ch3) 2 CH2CH3 77 6-MeO cf3 ch2ch2ch2ch3 ch2ch3 78 6-MeO cf3 ch2ch2ch3 ch2ch3 79 6-MeO cf3 CH2CH2-tBu ch2ch3 80 5,6-diF cf3 C ^ C-Pr H 81 5,6-diF cf3 C = C-Bu H 82 5,6_diF cf3 C ^ C-iBu H 83 5,6-diF cf3 C = C-tBu H 84 5,6-diF cf3 C = C-Me H 85 5,6-diF cf3 CH2C «H3 H 86 5,6-diF cf3 ch2c ^ c-ch2ch3 H 87 5,6-diF cf3 CH2CH2CH2CH2CH3 H 88 5,6-diF cf3 CH2CH2CH3 H (Please read the precautions on the back before filling this page) -117- Paper scale applicable Chinese National Standard (CNS) A4 size (210X297 mm) 587 078 Ministry of Economic Affairs Bureau of Standards employees consumer cooperatives printed Μ Β7 V. invention is described in (115)
89 5,6-diF cf3 CH2CHrtBu H 90 5,6-diF cf3 C = C-iPr ch3 91 5,6-diF cf3 C^C-Pr ch3 92 5,6-diF cf3 CeC-Bu ch3 93 5,6-diF cf3 C^C-iBu ch3 94 5,6-diF cf3 C = C-tBu ch3 95 5,6-diF cf3 C^C-Et ch3 96 5,6-diF cf3 C^C-Me ch3 97 5,6-diF cf3 C^C-Ph ch3 98 5,6-diF cf3 CH2C = C-CH3 ch3 99 5,6-diF cf3 ch2c=c-ch2ch3 ch3 100 5,6-diF cf3 ch2ch2ch(ch3)2 ch3 101 5,6-diF cf3 ch2ch2ch2ch3 ch3 102 5,6-diF cf3 CH2CH2CH3 ch3 103 5,6-diF cf3 CH2CH2-tBu ch3 104 5,6-diF cf3 C^C-iPr CH2CH3 105 5,6-diF cf3 C = C-Pr ch2ch3 106 5,6-diF cf3 C^C-Bu CH2CH3 107 5,6-diF cf3 C^C-iBu ch2ch3 108 5,6-diF cf3 C^C-tBu CH2CH3 109 5,6-diF cf3 C^C-Et CH2CH3 110 5,6-diF cf3 C^C-Me ch2ch3 111 5,6-diF cf3 CH2C = C-CH3 CH2CH3 112 5,6-diF cf3 ch2c«h2ch3 CH2CH3 113 5,6-diF cf3 CH2CH2CH(CH3)2 CH2CH3 114 5,6-diF cf3 ch2ch2ch2ch3 CH2CH3 115 5,6-diF cf3 ch2ch2ch3 ch2ch3 116 5,6-diF cf3 CH2CH2_tBu CH2CH3 117 6-F cf3 C^C-Pr H 118 6-F cf3 C^C-Bu H 119 6-F cf3 C^C-iBu H 120 6-F cf3 C^C-tBu H -118- (請先閱讀背面之注意事項再填寫本頁) 本紙張尺度適用中國國家標準(CNS ) Α4規格(210Χ 297公釐) 587078 kl B7 經濟部中央標準局員工消費合作社印製 五、發明説明( 116 $ I I I 121 6-F cf3 OC-Me H I I I 122 6-F cf3 ch2c-c-ch2ch3 H I 123 6-F cf3 ch2ch2ch2ch2ch3 H ^^^ I 請 124 6-F cf3 ch2ch2ch3 H 先I 閱 I 125 6-F cf3 CH2CH2-tBu H 讀 背- 126 6-F cf3 C^C-iPr ch3 面 I i $·Ί 項I 再 填·‘ 寫電 本 127 6-F cf3 C = C-Pr ch3 128 6-F cf3 C^C-Bu ch3 129 6-F cf3 C^C-iBu ch3 130 6-F cf3 C^C-tBu ch3 131 6-F cf3 C^C-Et ch3 頁I 132 6-F cf3 C^C-Me ch3 N^^ I I 133 6-F cf3 CH2C«H3 ch3 1 I 134 6-F cf3 ch2oc-ch2ch3 ch3 1 | 135 6-F cf3 CH2CH2CH(CH3)2 ch3 1 136 6-F cf3 ch2ch2ch2ch3 ch3 訂 137 6-F cf3 ch2ch2ch3 ch3 1 I 138 6-F cf3 CH2CHrtBu ch3 1 I 139 6-F cf3 C^C-iPr CH2CH3 1 1 140 6-F cf3 C = C_Pr ch2ch3 1 141 6-F cf3 C^C-Bu ch2ch3 1 t 1 142 6-F cf3 C^C-iBu CH2CH3 143 6-F cf3 C = C-tBu CH2CH3 144 6-F cf3 OC-Et ch2ch3 1 145 6-F cf3 C^C-Me CH2CH3 1 146 6-F cf3 CH2OC-CH3 CH2CH3 1 147 6-F cf3 ch2c^c-ch2ch3 CH2CH3 1 148 6-F cf3 ch2ch2ch(ch3)2 ch2ch3 1 1 149 6-F cf3 CH2CH2CH2CH3 CH2CH3 150 6-F cf3 CH2CH2CH3 CH2CH3 1 1 151 6-F cf3 CH2CH2.tBu ch2ch3 1 1 152 5-C1 cf3 C^C-iPr -119- H 1 1 1 1 1 本紙張尺度適用中國國家標準(CNS ) A4規格(210 X 297公釐) 587078 A7 B7 117 五、發明説明() 經濟部中央標準局員工消費合作社印製 153 5-C1 cf3 C^C-Pr H 154 5-C1 cf3 C^C-Bu H 155 5-C1 cf3 C^C-iBu H 156 5-C1 cf3 C^C-tBu H 157 5-C1 cf3 C^C-Et H 158 5-C1 cf3 C^C-Me H 159 5-C1 cf3 CH2C«H3 H 160 5-C1 cf3 ch2c=c_ch2ch3 H 161 5-C1 cf3 ch2ch2ch2ch2ch3 H 162 5-C1 cf3 CH2CH2CH(CH3)2 H 163 5-C1 cf3 ch2ch2ch2ch3 H 164 5-C1 cf3 ch2ch2ch3 H 165 5-C1 cf3 CH2CH2-tBu H 166 5-C1 cf3 C^C-iPr ch3 167 5-C1 cf3 C^C-Pr ch3 168 5-C1 cf3 C^C-Bu ch3 169 5-C1 cf3 C^C-iBu ch3 170 5-C1 cf3 C = C-tBu ch3 171 5-C1 cf3 C^C-Et ch3 172 5-C1 cf3 C^C-Me ch3 173 5-C1 cf3 CH2C^C-CH3 ch3 174 5-C1 cf3 ch2oc-ch2ch3 ch3 175 5-C1 cf3 ch2ch2ch(ch3)2 ch3 176 5-C1 cf3 ch2ch2ch2ch3 ch3 177 5-C1 cf3 CH2CH2CH3 ch3 178 5-C1 cf3 CH2CH2-tBu ch3 179 5-C1 cf3 C^C-iPr ch2ch3 180 5-C1 cf3 C^C-Pr CH2CH3 181 5-C1 cf3 OC-Bu ch2ch3 182 5-C1 cf3 C^C-iBu ch2ch3 183 5-C1 cf3 C = C-tBu CH2CH3 184 5-C1 cf3 C^C-Et ch2ch3 (請先閲讀背面之注意事項再填寫本頁) -120- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 587078 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明(118) 185 5-C1 cf3 C^C-Me ch2ch3 186 5-C1 cf3 ch2c = c-ch3 ch2ch3 187 5-C1 cf3 ch2c^c-ch2ch3 ch2ch3 188 5-C1 cf3 CH2CH2CH(CH3)2 ch2ch3 189 5-C1 cf3 ch2ch2ch2ch3 ch2ch3 190 5-C1 cf3 ch2ch2ch3 ch2ch3 191 5-C1 cf3 CH2CH2-tBu ch2ch3 192 5-F cf3 C^C-iPr H 193 5-F cf3 C^C-Pr H 194 5-F cf3 C^C-Bu H 195 5-F cf3 C^C-iBu H 196 5-F cf3 C = C-tBu H 197 5-F cf3 C^C-Et H 198 5-F cf3 C^C-Me H 199 5-F cf3 CH2C = C-CH3 H 200 5-F cf3 ch2c^c-ch2ch3 H 201 5_F cf3 ch2ch2ch2ch2ch3 H 202 5-F cf3 CH2CH2CH(CH3)2 H 203 5-F cf3 ch2ch2ch2ch3 H 204 5-F cf3 ch2ch2ch3 H 205 5-F cf3 CH2CH2_tBu H 206 5-F cf3 C^C-iPr ch3 207 5-F cf3 C^C-Pr ch3 208 5-F cf3 C^C-Bu ch3 209 5-F cf3 C = C_iBu ch3 210 5-F cf3 C = C-tBu ch3 211 5_F cf3 C^C-Et ch3 212 5-F cf3 C = C-Me ch3 213 5-F cf3 CH2C = C-CH3 ch3 214 5-F cf3 ch2c = c-ch2ch3 ch3 215 5-F cf3 CH2CH2CH(CH3)2 ch3 216 5-F cf3 ch2ch2ch2ch3 ch3 -121 - (請先閱讀背面之注意事項再填寫本頁) 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 587078 經濟部中央標準局員工消費合作社印製 A7 B7 119 五、發明説明() 217 5-F cf3 ch2ch2ch3 ch3 218 5-F cf3 CH2CH2-tBu ch3 219 5-F cf3 C^C-iPr ch2ch3 220 5-F cf3 C^C-Pr ch2ch3 221 5-F cf3 C^C-Bu CH2CH3 222 5-F cf3 C^C-iBu CH2CH3 223 5-F cf3 C^C-tBu CH2CH3 224 5_F cf3 C^C-Et CH2CH3 225 5-F cf3 OC-Me CH2CH3 226 5-F cf3 CH2C«H3 CH2CH3 227 5-F cf3 ch2c = c-ch2ch3 CH2CH3 228 5-F cf3 ch2ch2ch(ch3)2 CH2CH3 229 5-F cf3 ch2ch2ch2ch3 CH2CH3 230 5-F cf3 ch2ch2ch3 CH2CH3 231 5-F cf3 CH2CH2_tBu ch2ch3 232 5-Cl,6-F cf3 C^C-iPr H 233 5-Cl,6-F cf3 C^C-Pr H 234 5-Cl,6-F cf3 C^C-Bu H 235 5-Cl,6-F cf3 C^C-iBu H 236 5-Cl,6-F cf3 C = C-tBu H 237 5-Cl,6-F cf3 C^C-Et H 238 5-Cl,6-F cf3 C^C-Me H 239 5-Cl,6-F cf3 CH2C^C-CH3 H 240 5-Cl,6-F cf3 ch2c^c-ch2ch3 H 241 5-Cl,6-F cf3 CH2CH2CH(CH3)2 H 242 5-Cl,6-F cf3 ch2ch2ch2ch3 H 243 5-Cl,6-F cf3 ch2ch2ch3 H 244 5-Cl,6-F cf3 CH2CH2-tBu H 245 5-Cl,6-F cf3 C^C-iPr ch3 246 5-Cl,6-F cf3 C^C-Pr ch3 247 5_C1,6_F cf3 C = C-Bu ch3 248 5-Cl,6-F cf3 C^C-iBu ch3 -122- : :---讀II (請先閱讀背面之注意_事項再填寫本頁) 4 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 587078 Μ Β7 經濟部中央標準局員工消費合作社印製 五、發明説明 (120) I I I 249 5-Cl,6-F cf3 C = C-tBu ch3 I I I 250 5-Cl,6-F cf3 C^C-Et ch3 1 251 5_C1,6-F cf3 C^C-Me ch3 1 請 252 5-Cl,6-F cf3 CH2CeC-CH3 ch3 先1 閱 1 253 5-Cl,6-F cf3 ch2c^c-ch2ch3 ch3 I 讀 背- 254 5-Cl,6-F cf3 ch2ch2ch(ch3)2 ch3 Π 1 面 | 之 1 255 5-Cl,6-F cf3 ch2ch2ch2ch3 ch3 I ! 項 I 再 填·‘ 寫零 本7 頁1 256 5-Cl,6-F cf3 ch2ch2ch3 ch3 257 5-Cl,6-F cf3 CH2CH2-tBu ch3 258 6_C1,8-F cf3 C^C-iPr H 259 6-Cl,8-F cf3 C = C-Pr H 260 6 - Cl,8-F cf3 C^C-Bu H N^^ 1 261 6-Cl,8-F cf3 C^C-iBu H 1 I 262 6-Cl,8-F cf3 C = C-tBu H 1 I 263 6_C1,8-F cf3 C = C_Et H 1 1 264 6_C1,8-F cf3 C^C-Me H 訂 265 6-Cl,8-F cf3 CH2C^C-CH3 H 1 I 266 6-Cl,8-F cf3 ch2c=c-ch2ch3 H 1 I 267 6-Cl,8-F cf3 ch2ch2ch(ch3)2 H 1 1 268 6-Cl,8-F cf3 ch2ch2ch2ch3 H 1 269 6-Cl,8-F cf3 ch2ch2ch3 H 1 η I 270 6_C1,8-F cf3 CH2CHrtBu H 271 6-Cl,8-F cf3 C^C-iPr ch3 272 6-Cl,8-F cf3 C^C-Pr ch3 1 273 6-Cl,8-F cf3 C^C-Bu ch3 1 274 6-Cl,8_F cf3 C^C-iBu ch3 I 275 6-Cl,8-F cf3 C = C-tBu ch3 1 276 6-Cl,8-F cf3 C^C-Et ch3 1 | 277 6-Cl,8_F cf3 C = C-Me ch3 ch3 278 6-Cl,8-F cf3 CH2C^C-CH3 1 279 6_C1,8-F cf3 ch2c^c-ch2ch3 ch3 1 I 280 6-Cl,8-F cf3 CH2CH2CH(CH3)2 -123- ch3 1 1 1 1 1 本紙張尺度適用中國國家標準(CNS ) Α4規格(210X 297公釐) 587078 經濟部中央標準局員工消費合作社印製 Μ Β7 五、發明説明(121 )89 5,6-diF cf3 CH2CHrtBu H 90 5,6-diF cf3 C = C-iPr ch3 91 5,6-diF cf3 C ^ C-Pr ch3 92 5,6-diF cf3 CeC-Bu ch3 93 5,6 -diF cf3 C ^ C-iBu ch3 94 5,6-diF cf3 C = C-tBu ch3 95 5,6-diF cf3 C ^ C-Et ch3 96 5,6-diF cf3 C ^ C-Me ch3 97 5 , 6-diF cf3 C ^ C-Ph ch3 98 5,6-diF cf3 CH2C = C-CH3 ch3 99 5,6-diF cf3 ch2c = c-ch2ch3 ch3 100 5,6-diF cf3 ch2ch2ch (ch3) 2 ch3 101 5,6-diF cf3 ch2ch2ch2ch3 ch3 102 5,6-diF cf3 CH2CH2CH3 ch3 103 5,6-diF cf3 CH2CH2-tBu ch3 104 5,6-diF cf3 C ^ C-iPr CH2CH3 105 5,6-diF cf3 C = C-Pr ch2ch3 106 5,6-diF cf3 C ^ C-Bu CH2CH3 107 5,6-diF cf3 C ^ C-iBu ch2ch3 108 5,6-diF cf3 C ^ C-tBu CH2CH3 109 5,6-diF cf3 C ^ C-Et CH2CH3 110 5,6-diF cf3 C ^ C-Me ch2ch3 111 5,6-diF cf3 CH2C = C-CH3 CH2CH3 112 5,6-diF cf3 ch2c «h2ch3 CH2CH3 113 5,6-diF cf3 CH2CH2CH (CH3) 2 CH2CH3 114 5,6-diF cf3 ch2ch2ch2ch3 CH2CH3 115 5,6-diF cf3 ch2ch2ch3 ch2ch3 116 5,6-diF cf3 CH2CH2_tBu CH2CH3 117 6-F cf3 C ^ C-Pr H 118 6-F C ^ C-Bu H 119 6-F cf3 C ^ C-iBu H 120 6-F cf3 C ^ C-tBu H -118- (Please read first Please fill in this page again if you need to pay attention to this page) This paper size is applicable to Chinese National Standard (CNS) A4 specification (210 × 297 mm) 587078 kl B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs -F cf3 OC-Me HIII 122 6-F cf3 ch2c-c-ch2ch3 HI 123 6-F cf3 ch2ch2ch2ch2ch3 H ^^^ I Please 124 6-F cf3 ch2ch2ch3 H First I read I 125 6-F cf3 CH2CH2-tBu H Read back-126 6-F cf3 C ^ C-iPr ch3 Face I i $ · Ί Item I refill · 'Write a book 127 6-F cf3 C = C-Pr ch3 128 6-F cf3 C ^ C-Bu ch3 129 6-F cf3 C ^ C-iBu ch3 130 6-F cf3 C ^ C-tBu ch3 131 6-F cf3 C ^ C-Et ch3 page I 132 6-F cf3 C ^ C-Me ch3 N ^^ II 133 6-F cf3 CH2C «H3 ch3 1 I 134 6-F cf3 ch2oc-ch2ch3 ch3 1 | 135 6-F cf3 CH2CH2CH (CH3) 2 ch3 1 136 6-F cf3 ch2ch2ch2ch3 ch3 Order 137 6-ch ch3 ch3 ch2 1 I 138 6-F cf3 CH2CHrtBu ch3 1 I 139 6-F cf3 C ^ C-iPr CH2CH3 1 1 140 6-F cf3 C = C_Pr ch2ch3 1 141 6-F cf3 C ^ C-Bu ch2ch3 1 t 1 142 6 -F cf3 C ^ C-iBu CH2CH3 143 6-F cf3 C = C-tBu CH2CH3 144 6-F cf3 OC-Et ch2ch3 1 145 6- F cf3 C ^ C-Me CH2CH3 1 146 6-F cf3 CH2OC-CH3 CH2CH3 1 147 6-F cf3 ch2c ^ c-ch2ch3 CH2CH3 1 148 6-F cf3 ch2ch2ch (ch3) 2 ch2ch3 1 1 149 6-F cf3 CH2CH2CH2 CH2CH3 150 6-F cf3 CH2CH2CH3 CH2CH3 1 1 151 6-F cf3 CH2CH2.tBu ch2ch3 1 1 152 5-C1 cf3 C ^ C-iPr -119- H 1 1 1 1 1 This paper is applicable to the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 587078 A7 B7 117 V. Description of the invention () Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 153 5-C1 cf3 C ^ C-Pr H 154 5-C1 cf3 C ^ C-Bu H 155 5-C1 cf3 C ^ C-iBu H 156 5-C1 cf3 C ^ C-tBu H 157 5-C1 cf3 C ^ C-Et H 158 5-C1 cf3 C ^ C-Me H 159 5-C1 cf3 CH2C «H3 H 160 5-C1 cf3 ch2c = c_ch2ch3 H 161 5-C1 cf3 ch2ch2ch2ch2ch3 H 162 5-C1 cf3 CH2CH2CH (CH3) 2 H 163 5-C1 cf3 ch2ch2ch2ch2ch3 H 164 5-C1 cf3 ch2 ch2165 2 CH2CH2-tBu H 166 5-C1 cf3 C ^ C-iPr ch3 167 5-C1 cf3 C ^ C-Pr ch3 168 5-C1 cf3 C ^ C-Bu ch3 169 5-C1 cf3 C ^ C-iBu ch3 170 5 -C1 cf3 C = C-tBu ch3 171 5-C1 cf3 C ^ C-Et ch3 172 5-C1 cf3 C ^ C-Me ch3 173 5-C1 cf3 CH2C ^ C-CH3 ch3 174 5-C 1 cf3 ch2oc-ch2ch3 ch3 175 5-C1 cf3 ch2ch2ch (ch3) 2 ch3 176 5-C1 cf3 ch2ch2ch2ch3 ch3 177 5-C1 cf3 CH2CH2CH3 ch3 178 5-C1 cf3 CH2CH2-tBu ch3 P1-C1-C1-C1 ch2ch3 180 5-C1 cf3 C ^ C-Pr CH2CH3 181 5-C1 cf3 OC-Bu ch2ch3 182 5-C1 cf3 C ^ C-iBu ch2ch3 183 5-C1 cf3 C = C-tBu CH2CH3 184 5-C1 cf3 C ^ C-Et ch2ch3 (Please read the notes on the back before filling out this page) -120- This paper size is applicable to China National Standard (CNS) A4 specification (210X297 mm) 587078 Printed by A7 B7, a staff consumer cooperative of the Central Bureau of Standards, Ministry of Economic Affairs V. Description of the invention (118) 185 5-C1 cf3 C ^ C-Me ch2ch3 186 5-C1 cf3 ch2c = c-ch3 ch2ch3 187 5-C1 cf3 ch2c ^ c-ch2ch3 ch2ch3 188 5-C1 cf3 CH2CH2CH (CH3) 2 ch2ch3 189 5-C1 cf3 ch2ch2ch2ch3 ch2ch3 190 5-C1 cf3 ch2ch2ch3 ch2ch3 191 5-C1 cf3 CH2CH2-tBu ch2ch3 192 5-F cf3 C ^ C-iPr H 193 5-F cf3 C ^ C-Fr H 194 cf3 C ^ C-Bu H 195 5-F cf3 C ^ C-iBu H 196 5-F cf3 C = C-tBu H 197 5-F cf3 C ^ C-Et H 198 5-F cf3 C ^ C-Me H 199 5-F cf3 CH2C = C-CH3 H 200 5-F cf3 ch2c ^ c-ch2ch3 H 201 5_F cf3 ch 2ch2ch2ch2ch3 H 202 5-F cf3 CH2CH2CH (CH3) 2 H 203 5-F cf3 ch2ch2ch2ch3 H 204 5-F cf3 ch2ch2ch3 H 205 5-F cf3 CH2CH2_tBu H 206 5-F cf3 C ^ C-iPr ch3 207 5-F cf C ^ C-Pr ch3 208 5-F cf3 C ^ C-Bu ch3 209 5-F cf3 C = C_iBu ch3 210 5-F cf3 C = C-tBu ch3 211 5_F cf3 C ^ C-Et ch3 212 5-F cf3 C = C-Me ch3 213 5-F cf3 CH2C = C-CH3 ch3 214 5-F cf3 ch2c = c-ch2ch3 ch3 215 5-F cf3 CH2CH2CH (CH3) 2 ch3 216 5-F cf3 ch2ch2ch2ch3 ch3 -121- (Please read the precautions on the back before filling this page) This paper size is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm) 587078 Printed by the Consumers Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 119 V. Description of the invention () 217 5-F cf3 ch2ch2ch3 ch3 218 5-F cf3 CH2CH2-tBu ch3 219 5-F cf3 C ^ C-iPr ch2ch3 220 5-F cf3 C ^ C-Pr ch2ch3 221 5-F cf3 C ^ C-Bu CH2CH3 222 5-F cf3 C ^ C-iBu CH2CH3 223 5-F cf3 C ^ C-tBu CH2CH3 224 5_F cf3 C ^ C-Et CH2CH3 225 5-F cf3 OC-Me CH2CH3 226 5-F cf3 CH2C «H3 CH2CH3 227 5 -F cf3 ch2c = c-ch2ch3 CH2CH3 228 5-F cf3 ch2ch2ch (ch3) 2 CH2CH3 229 5-F cf3 ch2ch2ch2ch3 CH2CH3 230 5-F cf3 ch2ch2ch3 CH2CH3 231 5-F cf3 CH2CH2_tBu ch2ch3 232 5-Cl, 6-F cf3 C ^ C-iPr H 233 5-Cl, 6-F cf3 C ^ C-Pr H 234 5-Cl, 6-F cf3 C ^ C-Bu H 235 5-Cl, 6-F cf3 C ^ C-iBu H 236 5-Cl, 6-F cf3 C = C-tBu H 237 5-Cl , 6-F cf3 C ^ C-Et H 238 5-Cl, 6-F cf3 C ^ C-Me H 239 5-Cl, 6-F cf3 CH2C ^ C-CH3 H 240 5-Cl, 6-F cf3 ch2c ^ c-ch2ch3 H 241 5-Cl, 6-F cf3 CH2CH2CH (CH3) 2 H 242 5-Cl, 6-F cf3 ch2ch2ch2ch3 H 243 5-Cl, 6-F cf3 ch2ch2ch3 H 244 5-Cl, 6- F cf3 CH2CH2-tBu H 245 5-Cl, 6-F cf3 C ^ C-iPr ch3 246 5-Cl, 6-F cf3 C ^ C-Pr ch3 247 5_C1, 6_F cf3 C = C-Bu ch3 248 5- Cl, 6-F cf3 C ^ C-iBu ch3 -122-:: --- Read II (Please read the notes on the back before filling in this page) 4 This paper size applies to China National Standard (CNS) A4 specifications ( 210X297 mm) 587078 Μ B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (120) III 249 5-Cl, 6-F cf3 C = C-tBu ch3 III 250 5-Cl, 6-F cf3 C ^ C-Et ch3 1 251 5_C1,6-F cf3 C ^ C-Me ch3 1 Please 252 5-Cl, 6-F cf3 CH2CeC-CH3 ch3 first read 1 253 5-Cl, 6-F cf3 ch2c ^ c-ch2ch3 ch3 I read back-254 5-Cl, 6-F cf3 ch2ch2ch (ch3) 2 ch3 Π 1 side | of 1 255 5 -Cl, 6-F cf3 ch2ch2ch2ch3 ch3 I! Refill the item I · 'Write zero 7 Page 1 256 5-Cl, 6-F cf3 ch2ch2ch3 ch3 257 5-Cl, 6-F cf3 CH2CH2-tBu ch3 258 6_C1, 8-F cf3 C ^ C-iPr H 259 6-Cl, 8-F cf3 C = C-Pr H 260 6-Cl, 8-F cf3 C ^ C-Bu HN ^^ 1 261 6-Cl, 8- F cf3 C ^ C-iBu H 1 I 262 6-Cl, 8-F cf3 C = C-tBu H 1 I 263 6_C1, 8-F cf3 C = C_Et H 1 1 264 6_C1, 8-F cf3 C ^ C -Me H 265 6-Cl, 8-F cf3 CH2C ^ C-CH3 H 1 I 266 6-Cl, 8-F cf3 ch2c = c-ch2ch3 H 1 I 267 6-Cl, 8-F cf3 ch2ch2ch (ch3 ) 2 H 1 1 268 6-Cl, 8-F cf3 ch2ch2ch2ch3 H 1 269 6-Cl, 8-F cf3 ch2ch2ch3 H 1 η I 270 6_C1, 8-F cf3 CH2CHrtBu H 271 6-Cl, 8-F cf3 C ^ C-iPr ch3 272 6-Cl, 8-F cf3 C ^ C-Pr ch3 1 273 6-Cl, 8-F cf3 C ^ C-Bu ch3 1 274 6-Cl, 8_F cf3 C ^ C-iBu ch3 I 275 6-Cl, 8-F cf3 C = C-tBu ch3 1 276 6-Cl, 8-F cf3 C ^ C-Et ch3 1 | 277 6-Cl, 8_F cf3 C = C-Me ch3 ch3 278 6 -Cl , 8-F cf3 CH2C ^ C-CH3 1 279 6_C1,8-F cf3 ch2c ^ c-ch2ch3 ch3 1 I 280 6-Cl, 8-F cf3 CH2CH2CH (CH3) 2 -123- ch3 1 1 1 1 1 This paper size applies to China National Standard (CNS) Α4 size (210X 297 mm) 587078 Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs Β7. Invention Description (121)
281 6-Cl,8_F cf3 ch2ch2ch2ch3 ch3 282 6-Cl,8-F cf3 ch2ch2ch3 ch3 283 6-Cl,8-F cf3 CH2CH2-tBu ch3 284 6-CH3 cf3 C = C_iPr 285 6-CH3 cf3 C = C-Pr H 286 6-CH3 cf3 C^C-Bu Ή 287 6-CH3 cf3 C^C-iBu H 288 6-CH3 cf3 C^C-tBu H 289 6-CH3 cf3 C^C-Et H 290 6-CH3 cf3 C^C-Me H 291 6-CH3 cf3 CH2C^C-CH3 H 292 6-CH3 cf3 ch2c«h2ch3 H 293 6-CH3 cf3 ch2ch2ch(ch3)2 H 294 6-CH3 cf3 CH2CH2CH2CH3 H 295 6-CH3 cf3 ch2ch2ch3 H 296 6-CH3 cf3 CH2CH2-tBu H 297 6-CH3 cf3 C^C-iPr ch3 298 6_CH3 cf3 C = C-Pr ch3 299 6-CH3 cf3 C^C-Bu ch3 300 6-CH3 cf3 C^C-iBu ch3 301 6_CH3 cf3 C = C-tBu ch3 302 6-CH3 cf3 C^C-Et ch3 303 6-CH3 cf3 C = C-Me ch3 304 6-CH3 cf3 CH2C«H3 ch3 305 6-CH3 cf3 ch2c^c-ch2ch3 ch3 306 6-CH3 cf3 ch2ch2ch(ch3)2 ch3 307 6-CH3 cf3 ch2ch2ch2ch3 ch3 308 6-CH3 cf3 ch2ch2ch3 ch3 309 6-CH3 cf3 CH2CH2-tBu ch3 310 6-COCH3 cf3 C = C-iPr 311 6-COCH3 cf3 C^C-Pr H 312 6-COCH3 cf3 C^C-Bu H ---1--14------IT------蹲 · (請先閱讀背面之注意事項再填寫本頁) 124- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 587078 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明(122 ) 313 6-COCH3 cf3 C^C-iBu H 314 6-COCH3 cf3 C = C-tBu H 315 6-COCH3 cf3 C^C-Et H 316 6-COCH3 cf3 C^C-Me H 317 6-NH2 cf3 C^C-iPr H 318 6_NH2 cf3 C^C-Pr H 319 6_NH2 cf3 C^C-Bu H 320 6-NH2 cf3 C^C-iBu H 321 6-NH2 cf3 C = C-tBu H 322 6-NH2 cf3 C^C-Et H 323 6-NH2 cf3 C = C-Me H 324 6-NMe2 cf3 C^C-iPr H 325 6-NMe2 cf3 C = C-Pr H 326 6-NMe2 cf3 C^C-Bu H 327 6-NMe2 cf3 C^C-iBu H 328 6-NMe2 cf3 C = C-tBu H 329 6-NMe2 cf3 C^C-Et H 330 6-NMe2 cf3 C^C-Me H 331 7-C1 cf3 C^C-iPr H 332 7-C1 cf3 C = C-Pr H 333 7-C1 cf3 C^C-Bu H 334 7-C1 cf3 C^C-iBu H 335 7-C1 cf3 C-tBu H 336 7-C1 cf3 C^C-Et H 337 7-C1 cf3 C^C-Me H *除非特別提及,否則立體化學性是( + /-)。 -125- (請先閲讀背面之注意事項再填寫本頁) 本紙張尺度適用中國國家標準(CNS ) A4規格(210X 297公釐) 587078 經濟部中央標準局員工消費合作社印製 A7 ------------ B7 五、發明説明(123 ) ~ 用途 本發明化合物具有抑制逆轉綠酶的活性,明確言之 疋抑制HIV的A力。式⑴化合物具有抑制hiv逆轉綠酶 ㈣性,因而可作爲治療HIV感染及相關性疾病之抗病毒 樂劑,式⑴化合物具有抑制HIV逆轉錄酶活性,且可 爲抑制謂生長之抑制劑’可用病毒生長或感染性之棹準 分析法證明本發明化合物抑㈣毒生長或錢性之能力, 如利用後述之分析方法。 本發明式(I)化合物亦可抑制含有HIV之活體外樣品中 的HIV或是曾接觸HIV樣品中的則¥,因此,本發明化 合物可用以抑制含有或曾接觸HIV之體液樣品(如血清或 精液)中的HI V。 本發明提供之化合物亦可做爲測定藥劑抑制病毒純系複 製及/或HIV逆轉錄酶能力之試驗或分析方法的標準或參 考化合物,例如,用於藥學上研究之計晝。因此,本發明 化合物可作爲此種分析方法中之對照或參考化合物,並可 作爲品質控制的標準,市售套組或包裝中可附本發明化合 物以作爲此種標準或參考化合物。 因爲本發明化合物具有抑制ΗIV逆轉綠酶之專一性,因 此,本發明化合物亦可作爲偵測HIV逆轉綠酶之診斷方法 中之診斷試劑。於是,利用本發明化合物進行分析方法(諸 如本專利説明中所述之分析方法)的逆轉綠酶抑制性是爲 HI V逆轉綠酶及HIV病毒存在的指標。 本專利説明書中所用之”Mg”意指微克,”mg”意指毫 -126- 本紙張尺度適用中標準(CNsT^規格(21〇X297^t j '—— —— — I —I ——. ——· —— I —- 丁 n ϋ n n (請先閱讀背面之注意♦項再填寫本頁) 587078 經濟部中央標準局員工消費合作社印製 A7 B7五、發明説明(124 ) 克,”g”意指克,”μΐ/’意指微升,”L”意指公升,”nM”意 指毫微莫耳,”μΜ”意指微莫耳,”mM”意指毫莫耳,”M” 意指莫耳而nm”意指毫微米,”西格馬”是爲聖路易士, Μ Ο .之西格馬·阿耳瑞克公司。 HIV RNA分析方法 DNΑ質體及活體外RNA轉綠本: 根據愛耳克森-維特南(Erickson-Viitanen)等人,AIDS研 究及人類逆轉錄病毒1989,5,577.所述之方法將含有BH10 上邑&8及?〇1序列〇卩113-1816)之口0八672質體轉植至?丁2 19R上,用Bam HI將質體切成線狀,而後利用Riboprobe Gemini system II套組(蒲昧格)以T7 RNA聚合酶於活體外 產生RNA轉錄本,先利用不含RNase之DNAse(蒲昧格)處 理純化所合成之RN A,後以苯氣仿萃取,再進行酒精沉 澱,沉澱所得的RNA轉錄本溶解於水中,並保存在-70 °C,以A26q測定RNA的濃度。 探針: 利用Applied Biosystems(伏斯特城,CA)之DNA合成 儀,以古古主(Cocuzza),Tet. Lett. 1989,30,6287 之方法, 在寡核牮酸之5 ’端加上生物素,所合成之生物素化的捕捉 探針以HPLC純化,gag生物素化捕捉探針(5 ’ -生物素-CTAGCTCCCTGCTTGCCCATACTA 3,)與 HXB2 之核甞酸 889-912互補,而pol生物素化捕捉探針(5、生物素-CCCTATCATTTTTGGTTTCCAT 3’)貝丨J 與 HXB2 的核甞酸 2374-2395互補,利用Syngene(聖地牙哥,CA)製備做爲 -127- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) (請先閱讀背面之注意事項再填寫本頁) 經濟部中央標準局員工消費合作社印製 587078 Α7 Β7 五、發明説明(125) 報告探針之鹼嶙酸酶共耗寡核甞酸,pol報告探針(5, CTGTCTTACTTTGATAAAACCTC 3,)與 HXB2 核苷酸 2403-2425互補,而gag報告探針 (5’ CCCAGTATTTGTCTACAGCCTTCT 3,)貝丨]與 HXB2 核 答酸950-973互補,所有核贫酸位置是GenBank Genetic Sequence Data Bank 中的位置,業經 Genetics Computer Group Sequence Analysis Software Package (Devereau Nucleic Acids Research 1984,12,387)接受。報告探針是以 2 x SSC (0·3Μ NaCl,0.03M 擰檬酸鈉),0.05M Tris ρΗ8·8,1毫克/毫升BSA配成0.5 μΜ儲存液,生物素捕 捉探針則是以水配成1 00 μΜ儲存液。 抗生物素圖覆盤: 抗生物素圖覆盤是自杜邦生物科技系統(波士頓,Μ Α) 所得。 細胞及病毒材料: ΜΤ-2及ΜΤ-4細胞以含有2 mM L-麩胺酸及50微克/ 毫升吉特素(gentamycin)之RPMI 1640培養基培養,而 MT-2細胞添加5%的胎牛血清(FCS),MT-4添加10% FCS,HIV_1 RF是以相同培養基培養之MT_4細胞繁殖 的,在急性感染MT-4細胞後約10天後,製備病毒料,並 將病毒料分成小包裝保存於-70 °C下。HIV-1 (RF)料的感 染力價爲l_3xl07 PFU(溶胞形成單位(plaque forming units)/毫升,其是藉在ΜT - 2細胞上之溶胞分析方法測定 的(參考下文),每個用於感染時所用之病毒料小包裝祇能 -128- 本紙張尺度適用中國國家榡準(CNS ) Α4規格(210Χ 297公釐) I I I - I — I! ......-- - m I ·ϋ -I- I 丁— I I I I - : --- - Ψ" (請先閲讀背面之注意事項再填寫本頁) 587078 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明(126) 解康一次。 在進行評估抗病毒效力時,用於感染的細胞需在感染前 一天次培養,在感染的當天,將細胞重新懸浮於5% FCS RPMI培養基中(濃度爲5 X 1〇5細胞/毫升),進行大型感染 作用,或是將細胞懸浮於含有5% FCS之度貝克氏修飾伊 斯培養基(濃度爲2χ/106毫升),在微量盤中進行感染,加 入病毒並在37 °C下培養3天。 HIV RNA分析方法: 將細胞溶解物或是溶於31V[或5M GED之純化RNA與5M GED及捕捉探針混合,使異硫氰酸胍最終濃度爲3 μ,而 生物素寡核苷酸最終濃度爲30 ηΜ。37°C下,在密封U底 96槽孔組織培養盤(那克或柯斯塔)中進行雜化作用16_2〇 小時,用去離子水將RNA雜化作用反應稀釋3倍,使異硫 氰酸胍最終濃度爲1M,並分取少量(150微升)之反應液至 抗生物素圖覆微量盤之槽孔申,室溫下,將捕捉探針及捕 捉探針-RNA雜化物進行鍵結至固定的抗生物素反應2小 時,其後,用杜邦ELISA盤清洗緩衝液(磷酸緩衝鹽 (PBS) ’ 0.05% Tween 20)清洗微量盤6次,再添加120 μι 内含 4 X SSC ’ 0.66% Tritonx100,6.66%去離子曱酶 胺,1毫克/毫升BSA及5 nM報告探針之雜化溶液進行第 二次的雜化作用,以便將報告探針雜化至已固定化的捕捉 探針及雜化標的RNA上,於37 °C下雜化1小時後,再次 清洗微量盤6次,添加溶於緩衝液j (2.5 Μ二乙胺pH8.9 (JBL科技),i〇 mM MgCl2,5 mM醋酸鋅二水合物及5 -129- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) : : Φ-- 够* (請先閱讀背面之注意事項再填寫本頁) 訂 07 870 經濟部中央標準局員工消費合作社印製 A7 _____B7 五、發明説明(127 ) mM N-經基乙基·乙伸_二胺-三醋酸)之〇2 mM methylumbelliferyl phosphate (MUBP,JBL 科技)1〇〇 μΐ 以 測定固定化鹼性磷酸酶活性,將微量盤置於37 °C下培養, 利用微量盤勞光計(戴鈉特克)測定於3 6 5 nM波長激發時所 放出450 nM之螢光強度。 微量盤基礎化合物評估HIV-1感染MT_2細胞: 將欲評估的化合物溶解於DMS0中,並以培養基稀釋至 欲測最高濃度的2倍,而DMS0最高濃度爲2 %,進一步 在ϋ型底微量盤(那克)直接將化合物以組織培養基3倍連 續稀釋化合物,化合物連續稀釋之後,添加ΜΤ-2細胞(50 μΐ)使最終濃度爲每毫升含5 X 105細胞(每個槽孔中含有1 X 1 〇5細胞),將含有化合物之細胞置於3 7 t之二氧化碳培 養箱中培養3 0分鐘。評估化合物抗病毒潛力時,將適當稀 釋之HIV-1 (RF)病毒料(50 μΐ)加至内含細胞及待測化合物 稀釋液之培養盤槽孔中,每個槽孔的最終體積爲2〇〇 μ1, 其中每個培養盤有8個槽孔添加50 的培養基而不添加 病毒,而另8個槽孔是添加病毒卻不含有任何的抗病毒化 合物’評估化合物毒性時,培養類似培養盤但沒有任何病 毒感染。 置於3 7 C二氧化碳箱中之潮濕箱中培養3天後,從hi ν 感染之培養盤的每個槽孔中去除培養基祇留25 μΕ培養 基’將3 7 μί内含生物素化捕捉探針之5M GED添加至細 胞中’而每個槽孔中所剩培養基中最終GED爲3 Μ,捕捉 探針爲30 nM。在同一個用以病毒培養的微量盤中進行捕 -130- ^紙張尺度適用中國國家標準(CNS ) A4規格(2ΚΓΧ297公釐) -- ——I |_^ ——Φ------1T------ >* (請先閲讀背面之注意事項再填寫本頁) 587078 經濟部中央標準局員工消費合作社印製 Μ Β7五、發明説明(128 ) 捉探針與細胞溶解物之HI V RNA雜化作用,以微量盤封口 紙漿微量盤封口(柯斯塔),並於37 °C培養箱中培養16-20 小時,而後在每個槽孔中添加蒸餾水稀釋雜化反應液3 倍,再將此稀釋混合物移至抗生物素圖佈之微量盤中,以 前述之方法定量HIV RNA。在内含溶解但未感染之細胞槽 孔中添加已知含量之pDAB 72活體外RNA轉錄子所製備之 標準曲線可測定感染期間病毒所製造之RNA。 爲使評估化合物抗病毒活性時所用之病毒接種量標準 化,選擇能產生對二去氧胞嘧啶核苷(ddC)具IC9〇(需減少 HIV RNA量達90%之化合物濃度)數値爲0.2微克/毫升之 稀釋病毒,利用此步驟以數種HIV-1 (RF)病毒料進行實驗 時,其他抗病毒化合物之IC9〇數値(較ddC高或低者)均具 再線性,此濃度對應每個槽孔爲〜3xl05PFU(以MT-2細胞 所測之溶胞分析方法),且任何病毒接種量可產生約75%最 高病毒含量RNA。HIV RNA分析方法時,IC9〇是根據 RN A分析方法中所減低之淨訊號(感染細胞樣品的訊號減 去未感染細胞樣品之訊號)相較於同一個培養盤中感染但未 處理細胞之淨訊號(8個槽孔的平均値)所測。根據三種標 準進行每個感染及RNA分析方法,病毒感染時所產生之 RNA分析訊號需等於或大於2毫微克pDAB 72活體外轉錄 子所產生的訊號,進行每個分析方法時所測定之ddC的 IC9〇需介於0.1及0.3微克/毫升之間,最後,有效逆轉錄酶 抑制劑所產生之病毒RNA停滯期含量應低於未抑制感染量 的10%,假若化合物IC9〇低於20 μΜ,則表示該化合物具 -131 - (請先閱讀背面之注意事項再填寫本頁) 本紙張尺度適用中國國家標準(CNS ) Α4規格(210X297公釐) 587078 經濟部中央標準局員工消費合作社印製 A7 B7五、發明説明(129) 有活性。 進行抗病毒潛力測試時,所有在微量盤中進行者,第一 次添加2 X濃度化合物至單排槽孔後,均利用帕金愛耳馬/ 希特斯普羅派特。 蛋白質鍵結及突變抗性 爲了記述NNRTI在抗病毒潛能對漿蛋白臨床效力潛能, 及測定對抗野生型及突變型(在NNRTIs上已知之鍵結位置 發生了胺基酸的改變)HIV之抗病毒潛能。此測試理論具兩 方面意義: 1、 許多藥物能多方面的鍵結至漿蛋白上,雖然大 部分的藥物對主要的人體血漿成分(即人體血清蛋白(HSA) 或阿爾法-1 -酸醣蛋白(AAG))之鍵結親合力較低,但這些 主要的成分在血液中的濃度很高,只有游離或未鍵結之藥 物能穿越感染的細胞細胞膜,以便和標的位置(如HIV-1 逆轉錄酶,HIV-1RT)相互作用,因此,在組織培養中加入 HSA+AAG於抗病毒之潛能效應更能反應出某一化合物在 臨床試驗上之潛能。抑制90%病毒複製(以具意義病毒 RNA-基礎偵測方法測定之)時所須之化合物濃度定義爲 1C 90,在HS A及AAG存在下或添加HSA及AAG之試驗化 合物之表現IC9〇所增加的倍數反應出活體内的濃度(45毫 克/毫升HSA,1毫克/毫升AAG),增加的倍數越低,則 表示較多的化合物能與標的位置相互反應。 2、 由於感染個體中病毒高效率的複製及病毒RT較差 忠實度,因此導致感染個體中產生HIV的quasi-種或HIV -132- (請先閲讀背面之注意事項再填寫本頁) 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 587078 A7 ----- B7 五、發明説明(130) — 經濟部中央標準局員工消費合作社印製 混合種,运些種類包括了大部分的野生型,但亦包栝了 HIV的圖變型,而某—種突變型的比例反應出其相對的適 合性及複製率。由於突變型包括先前感染個體中之quasi-種上炙病毒RT胺基酸之改變,因此臨床試驗時所發現藥 物所抑制之整體潛能反應出的不只是野生型HIV-1 ,亦包 括野生型病毒。因此,根據已知遺傳知識背景,我們構築 HIV-1突變型’其在NNRTI鍵結位置上的胺基酸發生改 ’交,並測定待測化合物抑制這些突變病毒的能力。抑制 90 /。病母複製(以具意義病毒RNA-基礎偵測方法測定之)時 所須之化合物濃度疋義爲IC9〇,我們所要的是一種對各種 突變均具有高活性之化合物。 Μ量及調配物 在哺乳動物體中,利用任何與活性藥劑及藥劑作用位置 (如病毒逆轉綠酶)產生接觸的方法投用本發明抗病毒化合 物可治療病毒感染,其可用任何與藥學組合方式(或個別治 療藥劑或是治療藥劑的組合)傳統之方法投用,其可單獨使 用,但較佳的是根據所選用之投藥方式及標準醫藥程序與 醫藥载體使用。 當然,所用的劑量視許多因子而定,諸如特定藥劑的醫 藥動力學特性及其投藥模式與途徑;受體年齡,健康狀況 與把重,症狀的特性與程度,;同時治療的種類;治療的 頻率,及所欲的效果。每公斤體重之活性成分日記量約 〇·〇〇1至約1000毫克,較佳的劑量約0.1至約3毫克/公 斤0 ___ -133- ( CNS ) Α4ΐ^[ΊΓ〇 X 297^f ) 丨 II I! — — #! ·_ C請先閱讀背面之注意事項再填寫本頁) 、1Τ 經濟部中央標準局員工消費合作社印製 587078 Μ Β7 五、發明説明(131) 〜—'~ 一 適合投藥組合物之劑量形式中,每單位含有約i毫克至 約100毫克的活性成分,根據組合物的總重,這些=藥組 合物的活性成分通常是組合物總重的〇 重量比,活 性成分可以固態劑量形式經口投藥,諸如膠囊,二片及粉 末,或是液態劑量形式經口投藥,諸如補藥,糖漿及懸浮 液’其亦可以無菌的液態劑量形式非經腸投藥。 動物膠囊中含有活性成分及粉末载體,諸如乳糖,澱 粉·,纖維素衍生物,硬脂酸鎂,硬脂酸,及其類似者,相 似的稀釋劑可用以製備壓縮錠片。錠片及膠囊兩者可製成 持續性釋放出的形式,以便一段時間内能持續不斷的釋放 出藥劑,壓縮錠片可經糖圖覆或是以薄膜包覆,以掩飾令 人不悦的味道並能保護錠片,免於空氣的破壞,亦可以腸 衣包覆,以便在腸胃道中選擇性的分解。經口投藥之液態 劑量形式可含有成色記及芳香劑以增進病患的接受度。 通常水、合適的油脂、生理鹽水、葡萄糖水溶液及相關 的糖類溶液與乙二醇(諸如丙二醇或聚乙二醇)是非經腸投 藥所用溶液之適合的載體,非經腸投藥溶液較佳的是含有 水溶性之活性成分鹽類,適當的穩定劑,若有需要則含有 緩衝物質。抗氧化劑(諸如亞硫酸鈉或抗壞血酸,單獨使用 或混合使用)是合適的穩定劑,另外亦可使用擰檬酸及其鹽 類,與EDTA鈉鹽,除此之外,非經腸溶液中可含有保存 劑’如燒基二甲基芊基氯化按,對經基苯甲酸甲g旨或丙酯 與氣丁烷,適合的醫藥載體述於Remingt〇n,s Pharmaceutical Sciences,如前,爲此領域中的標準參考規 •134- 本紙張尺度適用中國國家標準(CNS ) A4規格Ϊ210Χ297公釐] " -- ---^---q---Φ-- ··· (請先閱讀背面之注意事項再填寫本頁)281 6-Cl, 8_F cf3 ch2ch2ch2ch3 ch3 282 6-Cl, 8-F cf3 ch2ch2ch3 ch3 283 6-Cl, 8-F cf3 CH2CH2-tBu ch3 284 6-CH3 cf3 C = C_iPr 285 6-CH3 cf3 C = C- Pr H 286 6-CH3 cf3 C ^ C-Bu Ή 287 6-CH3 cf3 C ^ C-iBu H 288 6-CH3 cf3 C ^ C-tBu H 289 6-CH3 cf3 C ^ C-Et H 290 6-CH3 cf3 C ^ C-Me H 291 6-CH3 cf3 CH2C ^ C-CH3 H 292 6-CH3 cf3 ch2c «h2ch3 H 293 6-CH3 cf3 ch2ch2ch (ch3) 2 H 294 6-CH3 cf3 CH2CH2CH2CH3 H 295 6-CH3 cf3 ch2ch2ch3 H 296 6-CH3 cf3 CH2CH2-tBu H 297 6-CH3 cf3 C ^ C-iPr ch3 298 6_CH3 cf3 C = C-Pr ch3 299 6-CH3 cf3 C ^ C-Bu ch3 300 6-CH3 cf3 C ^ C -iBu ch3 301 6_CH3 cf3 C = C-tBu ch3 302 6-CH3 cf3 C ^ C-Et ch3 303 6-CH3 cf3 C = C-Me ch3 304 6-CH3 cf3 CH2C «H3 ch3 305 6-CH3 cf3 ch2c ^ c-ch2ch3 ch3 306 6-CH3 cf3 ch2ch2ch (ch3) 2 ch3 307 6-CH3 cf3 ch2ch2ch2ch3 ch3 308 6-CH3 cf3 ch2ch2ch3 ch3 309 6-CH3 cf3 CH2CH2-tBu ch3 310 6-COCH3 cf-Ci3-6 -COCH3 cf3 C ^ C-Pr H 312 6-COCH3 cf3 C ^ C-Bu H --- 1--14 ------ IT ------ Squat (Please read the precautions on the back first (Fill in this page again) 124- This paper Degree applies to Chinese National Standard (CNS) A4 specification (210X297 mm) 587078 Printed by the Consumers' Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs A7 B7 V. Description of the invention (122) 313 6-COCH3 cf3 C ^ C-iBu H 314 6-COCH3 cf3 C = C-tBu H 315 6-COCH3 cf3 C ^ C-Et H 316 6-COCH3 cf3 C ^ C-Me H 317 6-NH2 cf3 C ^ C-iPr H 318 6_NH2 cf3 C ^ C-Pr H 319 6_NH2 cf3 C ^ C-Bu H 320 6-NH2 cf3 C ^ C-iBu H 321 6-NH2 cf3 C = C-tBu H 322 6-NH2 cf3 C ^ C-Et H 323 6-NH2 cf3 C = C- Me H 324 6-NMe2 cf3 C ^ C-iPr H 325 6-NMe2 cf3 C = C-Pr H 326 6-NMe2 cf3 C ^ C-Bu H 327 6-NMe2 cf3 C ^ C-iBu H 328 6-NMe2 cf3 C = C-tBu H 329 6-NMe2 cf3 C ^ C-Et H 330 6-NMe2 cf3 C ^ C-Me H 331 7-C1 cf3 C ^ C-iPr H 332 7-C1 cf3 C = C-Pr H 333 7-C1 cf3 C ^ C-Bu H 334 7-C1 cf3 C ^ C-iBu H 335 7-C1 cf3 C-tBu H 336 7-C1 cf3 C ^ C-Et H 337 7-C1 cf3 C ^ C-Me H * Unless specifically mentioned, stereochemistry is (+/-). -125- (Please read the notes on the back before filling in this page) This paper size is applicable to China National Standard (CNS) A4 size (210X 297 mm) 587078 Printed by the Consumer Standards Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A7 ---- -------- B7 V. Description of the invention (123) ~ Use The compound of the present invention has the activity of inhibiting the reversal of green enzymes, specifically, the ability to inhibit HIV A. The compound of formula (I) has the property of inhibiting the reversal of green enzyme by HIV, so it can be used as an antiviral agent for treating HIV infection and related diseases. The compound of formula (I) has the activity of inhibiting HIV reverse transcriptase, and can be used as an inhibitor of growth inhibition. A quasi-analytical method for virus growth or infectivity proves the ability of the compounds of the present invention to inhibit the growth or money of virulence, such as by using the analysis method described later. The compounds of formula (I) of the present invention can also inhibit HIV in in vitro samples containing HIV or have been exposed to HIV samples. Therefore, the compounds of the present invention can be used to inhibit body fluid samples (such as serum or Semen). The compound provided by the present invention can also be used as a standard or reference compound for a test or analysis method for determining the ability of a drug to inhibit virus pure replication and / or HIV reverse transcriptase, for example, for use in pharmaceutical research. Therefore, the compound of the present invention can be used as a reference or reference compound in such an analysis method, and can also be used as a standard for quality control. A commercially available kit or package can be accompanied by the compound of the present invention as such a standard or reference compound. Because the compound of the present invention has the specificity of inhibiting the reversion of lutetase IV to green enzyme, the compound of the present invention can also be used as a diagnostic reagent in a diagnostic method for detecting HIV reverse green enzyme. Therefore, the reversibility of green enzyme inhibition by the analytical method using the compound of the present invention (such as the analytical method described in this patent specification) is an indicator of the presence of HI V reverse green enzyme and HIV virus. "Mg" used in this patent specification means micrograms, and "mg" means milli-126- the standard applicable to this paper standard (CNsT ^ specification (21〇X297 ^ tj '—————— I —I —— —— · —— I —- ding n ϋ nn (please read the note on the back first and then fill out this page) 587078 A7 B7 printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs. “g” means grams, “μΐ / 'means microliters,“ L ”means liters,“ nM ”means nanomolar,“ μM ”means micromolar,“ mM ”means nanomolar, "M" means Mohr and nm "means nanometers, and" Sigma "is the Sigma Aleric company of Saint Louis, M .. HIV RNA analysis method DNA plastids and in vitro RNA to green: According to Erickson-Viitanen et al., AIDS Research and Human Retrovirus 1989,5,577. The method described will contain the BH10 shangyi & 8 and? 〇1 sequences.卩 113-1816) mouth 0-8 672 plastids were transplanted to? Ding 2 19R, the plastids were cut into lines with Bam HI, and then the Riboprobe Gemini system II kit (Pumig T7 RNA polymerase was used to generate RNA transcripts in vitro. The synthesized RN A was purified using DNAse (Pumeg) without RNase, and then extracted with benzene gas imitation, followed by alcohol precipitation, and the resulting RNA transcription was precipitated. This sample was dissolved in water and stored at -70 ° C, and the RNA concentration was measured with A26q. Probe: Using a DNA synthesizer from Applied Biosystems (Vost City, CA), Cocuzza, Tet. Lett 1989,30,6287 method, adding biotin to the 5 'end of oligonucleotide, the synthesized biotinylated capture probe was purified by HPLC, gag biotinylated capture probe (5'-biotin -CTAGCTCCCTGCTTGCCCATACTA 3,) is complementary to the nucleotide 889-912 of HXB2, and the pol biotinylated capture probe (5, biotin-CCCTATCATTTTTGGTTTCCAT 3 '), which is complementary to the nucleotide 2374-2395 of HXB2, utilizes Syngene (San Diego, CA) Prepared as -127- This paper size applies to the Chinese National Standard (CNS) A4 size (210X297 mm) (Please read the precautions on the back before filling this page) Staff of the Central Bureau of Standards of the Ministry of Economic Affairs Printed by the cooperative 587078 Α7 Β7 Description of the Invention (125) Alkaline enzyme co-consumptive oligonucleotide of reporter probe, pol reporter probe (5, CTGTCTTACTTTGATAAAACCTC 3,) is complementary to HXB2 nucleotide 2403-2425, and gag reporter probe (5 'CCCAGTATTTGTCTACAGCCTTCT 3,) 丨] Complementary with HXB2 nucleotides 950-973, all nuclear depleted acid positions are positions in the GenBank Genetic Sequence Data Bank and accepted by the Genetics Computer Group Sequence Analysis Software Package (Devereau Nucleic Acids Research 1984, 12,387). The reporting probe was prepared with 2 x SSC (0 · 3M NaCl, 0.03M sodium citrate), 0.05M Tris ρΗ8.8, 1 mg / ml BSA in 0.5 μM stock solution, and the biotin capture probe was water. Prepare a 100 μM stock solution. Avidin overlay: Avidin overlay was obtained from DuPont Biotechnology Systems (Boston, MA). Cells and viral materials: MT-2 and MT-4 cells were cultured in RPMI 1640 medium containing 2 mM L-glutamic acid and 50 μg / ml gentamycin, and MT-2 cells were supplemented with 5% fetal bovine Serum (FCS), MT-4 was added with 10% FCS, and HIV_1 RF was propagated in MT_4 cells cultured in the same medium. About 10 days after acute infection of MT-4 cells, virus material was prepared and the virus material was divided into small packages. Store at -70 ° C. The infectivity value of HIV-1 (RF) material is l_3xl07 PFU (plaque forming units / ml), which is determined by cytolytic analysis method on MT-2 cells (see below). The small package of virus material used for infection can only be -128- This paper size is applicable to China National Standard (CNS) Α4 size (210 × 297 mm) III-I — I! ......---m I · ϋ -I- I 丁 — IIII-: ----Ψ " (Please read the notes on the back before filling out this page) 587078 Printed by the Consumers Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Invention Description (126 Xie Kang once. When evaluating the antiviral efficacy, the cells used for infection need to be cultured one day before infection. On the day of infection, the cells are resuspended in 5% FCS RPMI medium (concentration: 5 X 105). Cells / ml), for large-scale infection, or suspend the cells in a Baker's Modified IS medium (concentration 2χ / 106 ml) containing 5% FCS and infect them in a microplate, add the virus and incubate at 37 ° Cultivate for 3 days at C. HIV RNA analysis method: Cell lysate or The purified RNA dissolved in 31V [or 5M GED was mixed with 5M GED and the capture probe to make the final concentration of guanidine isothiocyanate to 3 μ, and the final concentration of biotin oligonucleotide to 30 ηM. At 37 ° C, at Hybridization was performed in a sealed U-bottom 96-well tissue culture plate (Nak or Costa) for 16-20 hours, and the RNA hybridization reaction was diluted 3 times with deionized water, so that the final concentration of guanidine isothiocyanate was 1M. , And aliquot a small amount (150 microliters) of the reaction solution into the slot of the avidin-coated microplate. At room temperature, bind the capture probe and the capture probe-RNA hybrid to the fixed antibiotic. After reacting for 2 hours, the microplate was washed 6 times with DuPont ELISA plate washing buffer (phosphate buffered saline (PBS) '0.05% Tween 20), and 120 μm containing 4 X SSC' 0.66% Tritonx100, 6.66% was added. Deionized amylase, 1 mg / ml BSA and 5 nM reporter probe hybridization solution for the second hybridization in order to hybridize the reporter probe to the immobilized capture probe and hybrid target RNA After hybridization at 37 ° C for 1 hour, the microplate was washed again 6 times, and dissolved in buffer j (2.5 Diethylamine pH 8.9 (JBL Technology), i0mM MgCl2, 5 mM zinc acetate dihydrate and 5 -129- This paper size applies to China National Standard (CNS) A4 specification (210X297 mm): Φ-- Enough * (Please read the notes on the back before filling this page) Order 07 870 Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A7 _____B7 V. Description of the invention (127) mM N-Ethylethyl · Ethylene_Diamine -Triacetic acid) 〇2 mM methylumbelliferyl phosphate (MUBP, JBL Technology) 100μΐ To measure the activity of immobilized alkaline phosphatase, the microplate was cultured at 37 ° C, using a microplate luminometer (sodium diacetate) Turk) Determine the fluorescence intensity of 450 nM emitted when excited at a wavelength of 3 6 5 nM. Evaluation of HIV-1 infected MT_2 cells by microdisc basic compounds: Dissolve the compound to be evaluated in DMS0 and dilute to 2 times the highest concentration to be measured, and the highest concentration of DMS0 is 2%. (Nag) Directly dilute the compound 3 times in tissue culture medium. After serial dilution of the compound, add MT-2 cells (50 μΐ) to a final concentration of 5 X 105 cells per ml (1 X in each well). 105 cells), and the cells containing the compound were cultured in a 37 t carbon dioxide incubator for 30 minutes. When assessing the antiviral potential of a compound, an appropriately diluted HIV-1 (RF) virus stock (50 μΐ) was added to the wells of a culture dish containing cells and a dilution of the test compound. The final volume of each well was 2 〇〇μ1, where there are 8 wells with 50 medium without virus, and 8 wells with virus but no antiviral compound But there was no virus infection. After incubating for 3 days in a humidified 37 C carbon dioxide tank, remove the medium from each well of the hi ν infected culture plate and leave only 25 μE medium. '37 μL containing the biotinylated capture probe 5M GED was added to the cells' while the final GED in the remaining medium in each well was 3M and the capture probe was 30 nM. Captured in the same microplate used for virus culture -130- ^ Paper size applies Chinese National Standard (CNS) A4 specification (2KΓ × 297 mm)-——I | _ ^ ——Φ ------ 1T ------ > * (Please read the precautions on the back before filling out this page) 587078 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs Β7. V. Description of the invention (128) Capture probes and lysates For the hybridization of HI V RNA, seal the pulp tray with a microplate (costa), and incubate in a 37 ° C incubator for 16-20 hours, then add distilled water to each well to dilute the hybridization reaction solution. 3 times, and then transferred the diluted mixture to a microtiter plate of avidin cloth, and quantified HIV RNA by the method described above. A standard curve prepared by adding a known amount of pDAB 72 in vitro RNA transcripts to wells containing lysed but uninfected cells can measure RNA produced by the virus during infection. In order to standardize the amount of virus inoculation used in assessing the antiviral activity of a compound, the number of compounds capable of producing IC90 for dideoxycytosine nucleoside (ddC) (compound concentration required to reduce the amount of HIV RNA by 90%) was selected to be 0.2 μg / Ml of diluted virus, when using this step to perform experiments with several HIV-1 (RF) viral materials, the IC90 of other antiviral compounds (higher or lower than ddC) are relinear, and this concentration corresponds to each Each slot is ~ 3xl05PFU (based on the lysis analysis method of MT-2 cells), and any virus inoculation amount can produce about 75% of the highest virus content RNA. For the HIV RNA analysis method, IC90 is based on the net signal (signal of infected cell sample minus signal of uninfected cell sample) reduced in the RN A analysis method compared to the net signal of infected but untreated cells in the same culture plate. Signal (average of 8 slots). Each infection and RNA analysis method is performed according to three standards. The RNA analysis signal generated by the virus infection must be equal to or greater than 2 nanograms of pDAB 72 in vitro transcript. The ddC measured by each analysis method is The IC90 needs to be between 0.1 and 0.3 μg / ml. Finally, the content of viral RNA stasis produced by effective reverse transcriptase inhibitors should be less than 10% of the amount of uninhibited infection. If the compound IC90 is less than 20 μM, It means that the compound has -131-(Please read the precautions on the back before filling in this page) This paper size is applicable to China National Standard (CNS) A4 specification (210X297 mm) 587078 Printed by A7, Consumers Cooperative of Central Bureau of Standards, Ministry of Economic Affairs B7 V. Description of the invention (129) Active. For the antiviral potential test, all those who performed in the microplates, after the first addition of 2X concentration of compounds to a single row of wells, used Parkin Elma / Heterspropit. Protein binding and mutation resistance To describe the potential of NNRTI for its antiviral potential against plasma proteins, and to determine the resistance to wild-type and mutant (amino acid changes at the known binding positions on NNRTIs) HIV anti-virus Potential. This test theory has two meanings: 1. Many drugs can bind to plasma proteins in many ways, although most drugs have a major human plasma component (ie, human serum protein (HSA) or alpha-1 -acid glycoprotein). (AAG)) has a low affinity for bonding, but these main components are present in high concentrations in the blood, and only free or unbound drugs can cross the infected cell's cell membrane in order to reach the target location (such as HIV-1 reverse transcription Enzyme, HIV-1RT) interaction, so the potential effect of adding HSA + AAG in tissue culture on antiviral can better reflect the potential of a compound in clinical trials. The concentration of a compound required to inhibit 90% of viral replication (measured by a meaningful viral RNA-based detection method) is defined as 1C 90, the performance of test compounds in the presence of HS A and AAG or with HSA and AAG IC90. The increase factor reflects the concentration in vivo (45 mg / mL HSA, 1 mg / mL AAG). The lower the increase factor, the more compounds can react with the target position. 2. Due to the efficient replication of the virus and the poor loyalty of the virus RT in the infected individuals, the quasi-type or HIV-132- of HIV produced in the infected individuals (please read the precautions on the back before filling this page) Applicable to China National Standard (CNS) A4 specification (210X297 mm) 587078 A7 ----- B7 V. Description of invention (130) — Mixed species printed by the staff consumer cooperative of the Central Standards Bureau of the Ministry of Economic Affairs. These types include most of them Wild type, but it also contains a map variant of HIV, and the proportion of a certain mutant type reflects its relative suitability and replication rate. Because the mutant type includes changes in the amino acid of the quasi-species virus RT in previously infected individuals, the overall potential inhibited by the drug found in clinical trials reflects not only wild-type HIV-1, but also wild-type virus . Therefore, based on the background of known genetic knowledge, we construct HIV-1 mutants whose amino acids are changed at the NNRTI bonding site, and determine the ability of test compounds to inhibit these mutant viruses. Suppress 90 /. The concentration of the compound required for the replication of the mother (determined by a meaningful viral RNA-based detection method) is IC90. What we want is a compound with high activity against various mutations. The amount of M and its preparation in mammals can be treated by any method that makes contact with the active agent and the active site of the agent (such as virus reversal green enzyme). (Or individual therapeutic agents or a combination of therapeutic agents) traditional methods of administration, which can be used alone, but it is preferred to use according to the selected method of administration and standard medical procedures and pharmaceutical carriers. Of course, the dosage used will depend on many factors, such as the pharmacokinetic characteristics of the particular agent and its mode and route of administration; the age of the recipient, health status and weight, the nature and extent of symptoms; the type of simultaneous treatment; the type of treatment Frequency, and the desired effect. The daily amount of the active ingredient per kilogram of body weight is about 0.0001 to about 1000 mg, and the preferred dose is about 0.1 to about 3 mg / kg 0 ___ -133- (CNS) A4ΐ ^ [ΊΓ〇X 297 ^ f) 丨II I! — — #! · _ C Please read the notes on the back before filling out this page), 1T printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 587078 Μ Β7 5. Invention Description (131) ~ — '~ The dosage form of the administered composition contains about 1 mg to about 100 mg of the active ingredient per unit. According to the total weight of the composition, these = the active ingredient of the pharmaceutical composition is usually 0 weight ratio of the total weight of the composition. It can be administered orally in a solid dosage form, such as capsules, tablets, and powders, or in a liquid dosage form, such as tonics, syrups, and suspensions. It can also be administered parenterally in a sterile liquid dosage form. Animal capsules contain active ingredients and powder carriers such as lactose, starch, cellulose derivatives, magnesium stearate, stearic acid, and the like. Similar diluents can be used to prepare compressed tablets. Both tablets and capsules can be made into a sustained release form so that the medicament can be continuously released over a period of time. Compressed tablets can be coated with sugar maps or coated with a film to hide the unpleasant Taste and can protect the tablets from the damage of air, can also be coated with casings, so as to selectively break down in the gastrointestinal tract. Liquid dosage forms for oral administration may contain color formation and fragrances to improve patient acceptance. Water, suitable fats, normal saline, dextrose aqueous solution and related sugar solutions and ethylene glycol (such as propylene glycol or polyethylene glycol) are usually suitable carriers for parenteral solutions. Parenteral solutions are preferred Contains water-soluble active ingredient salts, suitable stabilizers, and buffer substances if necessary. Antioxidants (such as sodium sulfite or ascorbic acid, used alone or in combination) are suitable stabilizers. In addition, citric acid and its salts, and sodium EDTA can also be used. In addition, the parenteral solution may contain preservation Agents such as alkyl dimethyl sulfonyl chloride, p-methyl benzoate or propyl ester and gas butane, suitable pharmaceutical carriers are described in Remington, Pharmaceutical Sciences, as before, for this field Standard Reference Regulations in China • 134- This paper size applies to the Chinese National Standard (CNS) A4 size Ϊ210 × 297 mm] "---- ^ --- q --- Φ-- ··· (Please read the back first (Notes to fill out this page)
、1T 經濟部中央標準局員工消費合作社印製 587078 A7 ——_________ 五、發明説明(132 ) 範。 可用以投用本發明化合物的醫藥劑量形式説明如下: 敎 利用標準兩截式硬動物膠囊内裝100毫克粉末狀活性成 分’ 150毫克乳糖,50毫克纖維素及6毫克硬脂酸鎂,製 備大量之膠囊。 物膠囊 製備混合於可消化油脂中(如大豆油,棉子油或橄欖油) 之活性成分混合物,並利用正向取代唧筒將其填充至膠囊 中’以形成含有1 00毫克活性成分之動物膠囊,而後清洗 勝囊並乾燥。 蚊 利用傳統步驟大量製備單位劑量爲1 00毫克活性成分, 0·2亳克羽狀二氧化矽,5毫克硬脂酸鎂,275毫克微結晶 纖維素,11毫克澱粉及98.8毫克乳糖之錠片,可適當的 加以圖覆以增進可口性或延遲吸收性。 製備口服懸浮液,使5毫升懸浮液中含有2 5毫克細小顆 粒之活性成分,200毫克羥基甲基纖維素鈉,5毫克苯甲 酸鈉’ 1·〇克美國藥典之山梨糖醇溶液,及0.025克香草 酸0 丝射劑 攪拌10%體積比之丙二醇及水中的1 5%重量比之活性成 分’以製備適合注射投藥之非經腸組合物,以一般用的技 -135- 本紙張尺度適用中關家標準(CNS ) Α4規格(21GX297:釐)一— ; . Φ-- 罐 一 (請先閱讀背面之注意事項再填寫本頁) 、1Τ 587078 Μ --s------- Β7__ 五、發明説明(133 ) — ' 術消毒該溶液。 成分(a)及(b)之組合 (請先閱讀背面之注意事項再填寫本頁) 本發明之每個治療劑成分可單獨使用於任何劑量形式 中,如前所述,並可以各種方法投藥,如前所述。下列所 述之成分(b)是代表前述中一種或多種的藥劑,因此,假若 成分(a)及(b)可同時治療或單獨治療,則每個成分(b)可同 時治療或獨立治療。 經濟部中央標準局員工消費合作社印製 本發明成分(a)及(b)可一起調配在一個單一劑量單位中 (換言之,組合於一個膠囊,錠片,粉末或液體中)而成組 合式的產物,當成分(a)及(b)不一起調配在單一劑量單位 時,成分(a)可與成分(b)同時投藥,或是以任何順序投 藥;例如先投與本發明成分(a),再投與成分,或是以 相反的順序投藥’假若成分(b)中含有一種藥劑以上,如一 種R T抑制劑及一種蛋白酶抑制劑,則可一起投與這些藥 劑或以任何順序投藥,當不在同一時間投藥時,投與成分 (a)及(b)的間隔時間較佳是巧於一小時,成分(幻及(1))較 佳的投藥途徑是口服,本説明書中所用口服藥劑,口服抑 制劑,口服化合物,或其類物者意指經口投藥的化合物。 雖然化合物(a)及化合物(b)最好是以相同的途徑投藥(換言 之,例如兩者均爲口服)或是相同的劑量形式投藥,但若有 需要,亦可以不同的途徑投藥(換言之,例如組合產物中的 一種成分以口服方式投藥,而另一種成分以靜脈方式投藥) 或是以不同的劑量形式投藥。 熟於技藝之藥學開業者施以本發明組合治療的劑量視前 -136· 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 587078 kl --〜^五、發明説明(134) 經濟部中央標準局員工消費合作社印製 述各種因子(如#定藥劑的藥學動力特性及其模式與投藥途 傻,受體的年齡,健康狀況與體重,症狀的特性及嚴重 性,共同治療的種類,治療的頻率,所要的治療效果 定〇 根據本發明所揭示,熟於藥學開業者很容易了解本發明 成分(a)及(b)適當的劑量,一般標準而言, 劑量約丨。。毫克至約,·…假若成分(b)超過 以上,則成分(b)之每種藥劑曰劑量約1〇〇毫克至約i $ 克,一般標準而言,當組合投以成分(a)及成分(^時,則 每種成分的含量可減低約爲投以單一藥劑治療Ηιν感染時 之70_80% ’因爲組合式治療的相乘效果。 雖然活性成分是含於單一劑量單位中,但可調配本發明 組合式產物使活型成分間的生理接觸減至最低,例如爲了 減低接觸,該產物是經口投藥,而其中一種活性成分爲腸 衣圖覆,由於一種活性成分經腸衣圖覆,故其可能不祇可 降低組合活性成分間之接觸,亦可能在腸胃道中控制這些 成分中一種成分之釋放,因此這些成分中的一種成分能在 ,釋放出來而非在胃就釋放出來,本發明另一種具體實例 是提供的經口投藥之組合產物,其中_種活性成分是以持 續性釋放物質圖覆,效果是能在整個腸胃道中持續的釋 放,並且減低組合活性成分間的物質接觸,除此之外,持 續性釋放成分亦可另外以腸衣圖覆,如此該成分祇能在腸 中釋放。另外一種方法涉及組合產物的調配,其中一種成 分用持續即/或腸釋放聚合物圖覆,而另一種成分則以聚合 —-137- 適财關家標準格(2iGX297公籍)----——, 1T Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 587078 A7 ——_________ V. Description of Invention (132). The medicinal dosage forms for administering the compounds of the present invention can be described as follows: 敎 Using standard two-piece hard animal capsules containing 100 mg of powdered active ingredient '150 mg of lactose, 50 mg of cellulose and 6 mg of magnesium stearate, a large amount is prepared Capsule. Capsules to prepare active ingredient mixtures mixed with digestible fats (such as soybean oil, cottonseed oil, or olive oil) and fill them into capsules with a positive displacement capsule to form an animal capsule containing 100 mg of active ingredient , Then wash the capsule and dry. Mosquitoes use traditional procedures to prepare a large unit dose of 100 mg of active ingredient, 0.2 mg of feathery silica, 5 mg of magnesium stearate, 275 mg of microcrystalline cellulose, 11 mg of starch, and 98.8 mg of lactose. , Can be appropriately overlaid to improve palatability or delay absorption. An oral suspension was prepared so that 5 ml of the suspension contained 25 mg of finely divided active ingredients, 200 mg of sodium hydroxymethyl cellulose, 5 mg of sodium benzoate '1.0 g of sorbitol solution of the United States Pharmacopoeia, and 0.025 g Vanillic acid 0 spraying agent agitates 10% by volume of propylene glycol and 15% by weight of active ingredients in water to prepare parenteral compositions suitable for injection administration, using general techniques -135- Guan Jia Standard (CNS) Α4 specification (21GX297: centimeter) one-;. Φ-tank one (please read the notes on the back before filling this page), 1T 587078 Μ --s ------- Β7__ V. Description of the invention (133)-'Sterilize the solution. Combination of ingredients (a) and (b) (please read the notes on the back before filling this page) Each of the therapeutic agent ingredients of the present invention can be used individually in any dosage form, as described above, and can be administered in various ways As mentioned before. The component (b) described below represents one or more of the aforementioned agents. Therefore, if the components (a) and (b) can be treated simultaneously or separately, each component (b) can be treated simultaneously or independently. The Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs printed the ingredients (a) and (b) of the present invention and can be formulated together in a single dosage unit (in other words, combined in a capsule, tablet, powder or liquid) to form a combined Product, when ingredients (a) and (b) are not formulated together in a single dosage unit, ingredient (a) can be administered simultaneously with ingredient (b), or in any order; for example, the ingredient (a) of the present invention is administered first And then administer the ingredients, or in the reverse order. 'If ingredient (b) contains more than one agent, such as an RT inhibitor and a protease inhibitor, these agents can be administered together or in any order. When the drugs are not administered at the same time, the interval between the components (a) and (b) is preferably one hour, and the preferred route of administration of the components (magic and (1)) is oral. The oral agents used in this specification Oral inhibitors, oral compounds, or the like means a compound that is administered orally. Although compound (a) and compound (b) are preferably administered by the same route (in other words, both are administered orally) or by the same dosage form, they can also be administered by different routes if necessary (in other words, For example, one component of the combination product is administered orally and the other component is administered intravenously) or in different dosage forms. Pharmacy practitioners who are familiar with the technique apply the dose of the combination treatment of the present invention as before-136. This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) 587078 kl-~ ^ V. Description of the invention (134) The Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs printed various factors (such as the pharmacokinetic characteristics and mode of # 定 药 and the way they are administered, the age of the recipient, the health status and weight, the characteristics and severity of symptoms, and the common treatment of The type, the frequency of treatment, and the desired therapeutic effect are determined. According to the disclosure of the present invention, those skilled in pharmacy can easily understand the proper dosage of the ingredients (a) and (b) of the present invention. Generally speaking, the dosage is about 丨. Milligram to about ... If ingredient (b) exceeds the above, the dosage of each agent of ingredient (b) is about 100 milligrams to about i $ grams. Generally speaking, when ingredients (a) and Ingredients (^), the content of each ingredient can be reduced by about 70_80% when a single agent is used to treat Ηιν infection 'because of the multiplier effect of combined treatment. Although the active ingredient is contained in a single dosage unit, but The combination product of the present invention is formulated to minimize the physiological contact between the active ingredients. For example, in order to reduce the contact, the product is administered orally, and one of the active ingredients is an enteric coating. It may not only reduce the contact between the combined active ingredients, but also control the release of one of these ingredients in the gastrointestinal tract. Therefore, one of these ingredients can be released instead of being released in the stomach. A specific example is a combination product for oral administration, in which _ active ingredients are covered with a sustained release substance, the effect is that they can be continuously released throughout the gastrointestinal tract, and the material contact between the combined active ingredients is reduced, In addition, the sustained-release component can also be coated with an enteric coating, so that the component can only be released in the intestine. Another method involves the formulation of a combination product, in which one component is coated with a sustained- and / or enteric-release polymer, and The other ingredient is aggregated—-137- Shicai Guanjia Standard Cell (2iGX297 Citizenship) ----——
二· m - - I II - I n.i 11 - · ;---;I — 4I — ·- (請先閱讀背面之注意事項再填寫本頁) 、\5口 70 經濟部中央標準局員工消費合作社印製 A7 __—__B7 五、發明説明(135 ) 物圖覆,如低粘度級之甲基纖維素羥基丙基酯或是技藝中 已知之適當物質,以便能進一步區分活性成分。經由圖覆 或其他的物質可避免每種調配物中成分(a )及(b )的接觸, 亦可避免成分(b )中個別藥劑的接觸。 本發明組合產物之劑量形式中一種活性成分是腸衣圖 覆’其可爲錠片形式,而其他的活性成分混合一起,而後 在壓縮成一錠片,或是腸衣圖覆成分壓縮成衣錠片層,而 其他的活性成分蜃縮成另一層,另一種選擇是,爲了進一 步區分量層,存有一種或多種安慰劑層,如此的安慰劑層 是界於兩層活性成分層之間,除此之外,本發明劑量形式 可以膠囊形式存在,其中一種活性成分壓縮成錠片或是大 里微錠片,粒子,顆粒或n〇n-perils的形式,而後再腸衣 圖覆,將這些腸衣圖覆微錠片,粒子,顆粒或non_perils 置入膠囊或與其他活性成分的顆粒壓縮成膠囊中。 根據本發明所揭示,熟知技藝者明白這些與其他用以減 少本發明組合產物成分間之接觸的方法(不論是投與單一劑 量形式或是同一時間或以相同方法共同投與分離形式者)。 用以治療HIV感染之藥學套組含有具療效含量之藥學組 合物,在一個或多個無菌容器中包括成分(a)化合物及一種 或夕種成分(b)化合物,其亦爲本發明範圍之中。利用技藝 中所熟知之傳統消毒方法可消毒容器。成分(a)及成分(b) 可根據需要放在相同的無菌容器中,或是放在不同的無菌 容器中,或是放在一種或多種多區域容器中。成分(a)及成 为(b)可分開來,或是以物理性方式組合成前述單一劑量形 _ -138- 本紙張尺度適用中國國家標準(CNS ) A4規格(2i〇x]97公釐j -—- ---— I! — #! 0 (請先閱讀背面之注意事項再填寫本頁) 訂 587078 Μ _ Β7 ___ 五、發明説明(136 ) 式或單位,假若有需要,此種套組可包栝一種或多種各式 傳統醫藥套組成份,諸如一種或多種醫藥學上可接受之載 體,另含有混合成分用之小瓶等,此是熟知技藝者所明白 的,套組中亦包括插卡或標籤之指示,以説明成分投與份 量,投藥須知,及/或混合成份的指引。 明顯地,根據前述技術本發明有各種修飾及變化,因此 要了解的是在根據申請專利範圍之項目,本發明實際應用 上可與本説明書中所述不同。 ^ ^ 噃—丨 m · (請先閱讀背面之注意事項再填寫本頁} -訂 經濟部中央標準局員工消費合作社印製 -139 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐)· M--I II-I ni 11-·; ---; I — 4I — ·-(Please read the notes on the back before filling out this page), \ 5 口 70 Staff Consumer Cooperatives, Central Standards Bureau, Ministry of Economic Affairs Print A7 __—__ B7 V. Description of the invention (135) Object map, such as low-viscosity methylcellulose hydroxypropyl ester or appropriate substances known in the art, so that the active ingredients can be further distinguished. Through the map or other substances, the contact of the components (a) and (b) in each formulation can be avoided, and the contact of the individual agents in the component (b) can also be avoided. One of the active ingredients in the dosage form of the combination product of the present invention is an enteric coating, which can be in the form of tablets, and the other active ingredients are mixed together, and then compressed into a tablet, or the enteric coating is compressed into a coating tablet layer. While other active ingredients are curled up into another layer, another option is to store one or more placebo layers in order to further distinguish between the quantitative layers. Such a placebo layer is bounded between two active ingredient layers, in addition to this In addition, the dosage form of the present invention can be in the form of a capsule, in which one of the active ingredients is compressed into a tablet or a ali micro-tablet, in the form of particles, granules or non-perils, and then the casing pictures are overlaid, and these casing pictures are overlaid Tablets, granules, granules or non_perils are placed in capsules or compressed into capsules with granules of other active ingredients. Based on the disclosure of the present invention, those skilled in the art will understand these methods (whether administered in a single dose form or co-administered in separate forms at the same time or in the same method) to reduce the contact between the components of the combination product of the present invention. The pharmaceutical kit for treating HIV infection contains a therapeutic content of a pharmaceutical composition, which includes the component (a) compound and one or more component (b) compounds in one or more sterile containers, which are also within the scope of the present invention. in. Containers can be sterilized using conventional sterilization methods known in the art. Ingredients (a) and (b) can be placed in the same sterile container as required, or in different sterile containers, or in one or more multi-zone containers. Ingredients (a) and (b) can be separated or physically combined into the aforementioned single dose form. -138- This paper size applies to China National Standard (CNS) A4 specification (2i0x) 97 mm j -—- ---— I! — #! 0 (Please read the notes on the back before filling out this page) Order 587078 Μ _ Β7 ___ V. Description of the invention (136) Formula or unit, if necessary, this set A pack can contain one or more of various traditional medical kit components, such as one or more pharmaceutically acceptable carriers, and vials containing mixed ingredients, which are well known to those skilled in the art. The kit also includes The instructions of the card or label to explain the dosage of ingredients, instructions for administration, and / or guidelines for mixing ingredients. Obviously, the present invention has various modifications and changes according to the aforementioned technology, so it is important to understand that Project, the present invention may be different from the one described in this specification in actual application. ^ ^ 噃 — 丨 m · (Please read the notes on the back before filling out this page} -Order printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs- 139 paper sizes Applicable to China National Standard (CNS) A4 specification (210X297 mm)
Claims (1)
Applications Claiming Priority (2)
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US83854097A | 1997-04-09 | 1997-04-09 | |
US7132298P | 1998-01-14 | 1998-01-14 |
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TW087105365A TW587078B (en) | 1997-04-09 | 1998-04-15 | 4,4-disubstituted-3,4-dihydro-2(1H)-quinazolinones useful as HIV reverse transcriptase inhibitors |
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EP (1) | EP0973753A2 (en) |
JP (1) | JP2002504095A (en) |
KR (1) | KR20010006146A (en) |
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AR (1) | AR012340A1 (en) |
AU (1) | AU734928B2 (en) |
BR (1) | BR9808513A (en) |
CA (1) | CA2284996A1 (en) |
EA (1) | EA001991B1 (en) |
EE (1) | EE9900452A (en) |
HR (1) | HRP980143A2 (en) |
HU (1) | HUP0001446A3 (en) |
IL (1) | IL132188A0 (en) |
NO (1) | NO314936B1 (en) |
NZ (1) | NZ500592A (en) |
PL (1) | PL336305A1 (en) |
SK (1) | SK137899A3 (en) |
TW (1) | TW587078B (en) |
WO (1) | WO1998045276A2 (en) |
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1998
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- 1998-04-07 HU HU0001446A patent/HUP0001446A3/en unknown
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- 1998-04-07 EE EEP199900452A patent/EE9900452A/en unknown
- 1998-04-07 BR BR9808513-1A patent/BR9808513A/en not_active IP Right Cessation
- 1998-04-07 SK SK1378-99A patent/SK137899A3/en unknown
- 1998-04-07 EP EP98913401A patent/EP0973753A2/en not_active Withdrawn
- 1998-04-07 WO PCT/US1998/006733 patent/WO1998045276A2/en not_active Application Discontinuation
- 1998-04-07 KR KR1019997009225A patent/KR20010006146A/en not_active Application Discontinuation
- 1998-04-07 AU AU67960/98A patent/AU734928B2/en not_active Ceased
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- 1998-04-07 CA CA002284996A patent/CA2284996A1/en not_active Abandoned
- 1998-04-15 TW TW087105365A patent/TW587078B/en active
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1999
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WO1998045276A2 (en) | 1998-10-15 |
EP0973753A2 (en) | 2000-01-26 |
EA199900907A1 (en) | 2000-04-24 |
IL132188A0 (en) | 2001-03-19 |
NO994904D0 (en) | 1999-10-08 |
NZ500592A (en) | 2001-09-28 |
HRP980143A2 (en) | 1999-02-28 |
JP2002504095A (en) | 2002-02-05 |
SK137899A3 (en) | 2000-05-16 |
NO314936B1 (en) | 2003-06-16 |
EE9900452A (en) | 2000-04-17 |
PL336305A1 (en) | 2000-06-19 |
BR9808513A (en) | 2000-05-23 |
CN1252063A (en) | 2000-05-03 |
NO994904L (en) | 1999-12-01 |
EA001991B1 (en) | 2001-10-22 |
AU6796098A (en) | 1998-10-30 |
WO1998045276A3 (en) | 1999-01-14 |
HUP0001446A3 (en) | 2001-11-28 |
KR20010006146A (en) | 2001-01-26 |
AU734928B2 (en) | 2001-06-28 |
AR012340A1 (en) | 2000-10-18 |
CA2284996A1 (en) | 1998-10-15 |
HUP0001446A2 (en) | 2001-05-28 |
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