CA2000130A1 - N-sulfenylated and n-acylated pyrazolines - Google Patents
N-sulfenylated and n-acylated pyrazolinesInfo
- Publication number
- CA2000130A1 CA2000130A1 CA 2000130 CA2000130A CA2000130A1 CA 2000130 A1 CA2000130 A1 CA 2000130A1 CA 2000130 CA2000130 CA 2000130 CA 2000130 A CA2000130 A CA 2000130A CA 2000130 A1 CA2000130 A1 CA 2000130A1
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- co2me
- oet
- ipr
- ocf3
- tbu
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Abstract
TITLE
N-SULFENYLATED AND N-ACYLATED PYRAZOLINES
Abstract of the Disclosure N-sulfenylated and N-acylated pyrazoline arthropodicides, compositions containing them and methods for controlling arthropods by applying compounds of the invention to them or to their environment. The pyrazolines are selected from those of Formulae I to III wherein R1, R2, R3, Q, A, B, J, K, Y, m, n and p are as defined in the text:
I II
.
III
N-SULFENYLATED AND N-ACYLATED PYRAZOLINES
Abstract of the Disclosure N-sulfenylated and N-acylated pyrazoline arthropodicides, compositions containing them and methods for controlling arthropods by applying compounds of the invention to them or to their environment. The pyrazolines are selected from those of Formulae I to III wherein R1, R2, R3, Q, A, B, J, K, Y, m, n and p are as defined in the text:
I II
.
III
Description
Z ~ 30 ~L~ 2A-8766-C
N-SULF~NYLATED AND N-ACYLATED PYRAZOLINES
' Back~round of the Invention The following publications disclose pyrazolines:
U.S. 4,070,365 EPA 21,506 10 U.S. 4~156,007 EPA 58,424 V.S. 4,174,393 EPA 65,334 U.S. 4,663,341 EPA 113,213 WO B8/05046 EPA 153,127 Wo 88/07994 EPA 286,346 lS WO 89~00562 EPA 300,692 Grosscurt et al., ; ~ A~ric._Eood Chem., Vol. 27, No. 2 (1979).
.~
This application is a cognate of U.S. applica-tions 07/299,881 and 07J304,011.
Summary of the InventiQn - This invention pertains to compounds of Formulae I, II and III, including all geometric and stereo-i isomers, agriculturally suitable salts thereof, .; .
compositions containing them and their use as arthropodicides in agricultural and home uses.
; Hereafter, the compounds, isomers and salts are referred to as compound(s) for the sake ofsimplicity. The compounds ~re:
.
' "
".
. ,.
, . ~ - , . . . : . .
N-SULF~NYLATED AND N-ACYLATED PYRAZOLINES
' Back~round of the Invention The following publications disclose pyrazolines:
U.S. 4,070,365 EPA 21,506 10 U.S. 4~156,007 EPA 58,424 V.S. 4,174,393 EPA 65,334 U.S. 4,663,341 EPA 113,213 WO B8/05046 EPA 153,127 Wo 88/07994 EPA 286,346 lS WO 89~00562 EPA 300,692 Grosscurt et al., ; ~ A~ric._Eood Chem., Vol. 27, No. 2 (1979).
.~
This application is a cognate of U.S. applica-tions 07/299,881 and 07J304,011.
Summary of the InventiQn - This invention pertains to compounds of Formulae I, II and III, including all geometric and stereo-i isomers, agriculturally suitable salts thereof, .; .
compositions containing them and their use as arthropodicides in agricultural and home uses.
; Hereafter, the compounds, isomers and salts are referred to as compound(s) for the sake ofsimplicity. The compounds ~re:
.
' "
".
. ,.
, . ~ - , . . . : . .
2~3~(~130 ' ' " .
( RZ ) n~ R3 ~ P ~ 3 ) "
1 Q N~N N~X
x T H ~( Rl ) m ~a~( Rl ) m II .
` ., ,' . .
;'` A J.
~,~ O
.
~, .
wherein .j'!;'' A is a 1, 2 or 3-atom bridge ~omprising O ~o 3 i......................... carbon atoms, 0 to 1 o~ygen atoms, NR6, or .i 35 StO)q, wherein each carbon individually.can be sùbstituted with 1 to 2 substituents- .
selected from 1 to 2 balogen, Cl to C6 alkyl, ., .
':
.1 . , .
.~ , .
,',~, ' , -Z~ 30 C2 to C4 alkoxycarbonyl or phenyl optionally substituted with 1 to 3 substituents independently ~elected from W and one of the carbon atoms can be c~mbined into the group C(O) or C(S); .
H is H, Cl to C6 al~yl, C4 to C7 cycloalkyl alkyl, C3 to C6 cycloalkyl optionally substituted with 1 to 2 halogens or 1 to 2 CH3; Cl to C6 haloalkyl, C2 to C6 alkenyl, C2 to C6 haloalkenyl, C2 to C6 alkynyl, OR7, C2 ':r to C6 alkoxyalkyl, C2 to C6 cyanoalkyl, C3 to C8 alkoxycarbonylalkyl, CO2R4, C(O)R4, C(O)NR4Rs, C(S)NR4Rs, C(S)R4, C(S)~R~, phenyl, phenyl substituted by (R14)p, benzyl, or benzyl substituted with 1 to 3 substituents independently selected from W;
.: J is H, Cl to C4 alkyl or phenyl optionally substituted with W;
: R is H or CH3;
q is 0, 1 or 2;
. R1, R2, R3 and R14 are independently selected / from R4, halogen, CN, N3, SCN, NO2, OR4, SR4, :.~ 25 S(O)Rg~ S(O)2R4, OC(O)Rq~ OS(O)2R4, CO2R4, C(O)R4~ C(O)NR4R5~ S()2NR4R5~ NR4R5, NRSC(O)R4, OC(O)NHR~, NR5C(O)NHR4 and .~
NR5S(O)2R4: or w~en m, n or p is 2, Rl, R2, :-;; R3 or 214 can independently be tahen together ~. 30 as OCH2O, OCH2CH2O or CH2CH2O, to form a ~ or .
-~ 6-membere~ ring, each of which can be independently substituted with 1 to 4 halogen atoms or 1 to 2 methyl groups;
: R4 is selected from H, Cl to C6 alkyl, C3 to C6 cycloalkyl, C3 to C8 alko~ycarbonylalkyl, C3 to C6 alkenyl, C3 to C6 alkynyl, Cl to C6 ` ' ' .
, :
- , . . .
2~ 130 ':
haloalkyl, C3 to C6 haloalkenyl, Cl to C6 alkyl substituted with CN, CO2CH3, CO2CH2CH3, - OCH3~ OCH2CH3~ SCH3, ~CH2CH3 or NO2, or R4 is phenyl or benzyl, ~either optionally substituted with W; or R4 3nd R5 can be taken together as (CH2)4, (CH2)~ or CH2CH2OCH2CH2;
R5 is selected from H, Cl to C4 alkyl, C3 to C4 . .
.: 10 alkenyl, C3 t~ C4 alkynyl or Cl to C4 halo- ~ ~
alkyl; ~ ;
m, D and p are independently 1 to 3;
W is halogen, CN, NO2, Cl to C2 alkyl, Cl to C2 haloalkyl, Cl to C2 alko~Y, Cl to C2 halo ;~ 15 alkoxy, Cl to C2 alkylthio, Cl to C2 halo- :.
alkylthio, Cl to C2 alkylsulfonyl or Cl to C2 hal~alkylsulfonyl;
R6 is H, Cl to C4 alkyl, Cl to C4 haloalkyl, C2 to C4 alkenyl, C2 to C4 haloalkenyl, phenyl .. 20 optionally substituted with W or benzyl optionally substituted with W;
R7 is H, Cl ts C4 alkyl, C2 to C4 alkenyl, C2 to :
C4 alkynyl, C2 to C4 alkylcarbonyl, C2 to C4 ~, alko~ycarbonyl or Cl-C4 alkylsulfonyl;
~; 25 Q is SX, C2 to C22 alko~ycarbonyl, C2 to C22 haloalkoxycarbonyl, C7 to C15 pheno~ycarbonyl ; optionally substituted with 1 to 3 substi- :
tuents selected from W; C7 to C15 phenyl . carbonyl optionally substituted with 1 to 3 j.
~ 30 substituents independently selected from W;
-i C~ to C22 alkyl carbonyl, C2 to C22 haloalkyl carbonyl, CHO, C(O)CO2R5, or C8 to C12 ben- .
. zylo~ycarbonyl optionally substituteD with 1 : to 3 substituents independently ~elected from ., ~ .
., ~ .
..
', . : .
2t~ 3~
W; when Q is other than SX, R3 is other than C~2R4~ C(O)R4~ SO2NR3R4 or CONR4R5;
Y is C5 to C22 alkyl, C2 to C22 haloalkyl, C5 to C22 alkoxyalkyl, C4 to C22 alko~yalkoxyalkyl, C5 to C12 alkylthio, C5 to C12 haloalkylthio, ; C5 to C22 alkylcarbonyl, C5 to C22 haloalkylcarbonyl, C5 to C22 alkoxycarbonyl, . 10 C3 to C22 haloalkoxycarbonyl, or ~X;
Z is C7 to C22 alkyl~ C2 to C22 haloalkyl, C7 to C22 alko~yal~yl, C4 to C22 alko~yalko~yalkyl, C7 to C12 alkylthio, C7 to C12 haloalkylthio, C7 to C22 alkylcarbonyl, C7 to C22 :: 15 haloalkylcarbonyl, C7 to C2~ alko~ycarbonyl, C3 to C~2 haloalkoxycarbonyl or SX;
.
~ 20 X ~s NR8CRg, NR85~)aRg, NR8~ NR8P~ ;
~R9 PI~OR1O NRBR12 Or SR10 ~I - X~ ~ X1 ~8 R~ and R12 are independently Cl to C6 alkyl, ~; Cl to C6 haloalkyl, C3 to C6 cycloalkyl, C4 to . 30 C7 cycloalkylalkyl, phenyl optionally substituted by 1 to 2 substituents selected ` from W, benzyl optionally substituted by 1 to 2 substituents independently selected ~rom W, : phenethyl optionally substituted by 1 to 2 substituents independently selectea from W, C2 `~
to C6 cyanoalkyl, C2 to C6 alko~yalkyl, C3 to .'.. . .
", ~ . ., .. ~' 2~ 30 C8 alkoxycarbonylalkyl, C4 to C8 dialkylaminocarbonylalkyl; or RH and R12 can be - taken together as (CH2)4, (CH2)5 or (CH2~20(CH2)2' Rg is F, Cl to C22 alkyl, C3 to C6 cycloalkyl, C3 to C6 cycloalko~y, C2 to C8 dialkylamino, Cl to C6 haloalkyl, phenyl or pheno~y eithes optionally substituted by 1 to 2 substituents independently selected from W; Cl to C22 . alkoxy, Cl to C4 alkoxy substituted by cyano, nitro, C2 to C4 alko~y, C4 to C8 alko~yalko~y, Cl to C2 alkylthio, C2 to C3 alko~ycarbonyl, C3 to C5 dialkylaminocarbonyl, phenyl or 1 to 6 halogens; or Rg is morpholino, piperidino or . pyrrolidino, l-naphthosy, 2,2-dimethyl-2,3-- dihydrobenzofurano~y-7 or ON~sC~CH3)SCH3; :
. Rlo and Rll are independently Cl to C4 alkyl, C2 to C4 haloalkyl or phenyl optionally i substituted by 1 to 2 substituents ...
independently selected from W: or Rlo and Rll .' can be taken together as (CH2)2, (CH233 or CH2C(CH3)2CH2;
Y~ is S or O; and :
- a is 0 to 2. ~.
., ~' .
. Preferred compounds A are those of Formula I, Il or III wherein: :
-~ 30 Rl, R2, R3 and R14 are independently R4, CO2R4, ~rl halogen, CN, NO2, OR4, SR4, S(O)R4, S(O)2R4 or NR4R5, or when m, n or p is 2; .. :
Rl, ~2~ R3 or R14 can be taken together as OCH2O, x OCH2CH2O or CH2CH2O, each of which can be :y 35 substituted with 1 to 4 halogen ~toms or 1 to 2 ~:
; methyl groups;
~, .
s :~, . , . ~(, . . -- -2~ 13~
R4 is Cl to C2 alkyl, C3 to C4 alkenyl, Cl to C2 haloalkyl, C3 to C4 haloalkenyl or phenyl optionally substituted with halogen;
R5 is H or-Cl to C2 alkyl;
Q is S~, CHO, C2 to C6 alkoxycarbonyl, C2 ~ to C6 haloalko~ycarbonyl, C2 to C6 alkyl-: . carbonyl, C2 to C4 haloalkylcarbonyl, C7 to C10 phenosycarbonyl, C7 to C10 phenylcarbonyl or C8 to ClO benzylo~Y
carbonyl each pheno~y, phenyl ~r benzyl-o~y group optional~y ~ubstituted with 1 ~ to 2 substituents selected from W;
15 X is Xl, X2, X3, X4 or Xs;
- R8 and R12 are independently Cl to C6 alkyl, Cl to C6 haloalkyl, CS to C6 cycloalkyl, ` C3 to C8 alko~ycarbonylalkyl, phenyl, benzyl or phenethyl, each optionally ~ independently substituted with W; or R8 and R12 can be taken together as (CH2)4, (cH2~5 or (CH2)2O(cH2)2;
. R1o and Rll are independently Cl to C3 alkyl ~` or phenyl;
; 25 a is 2; .
. Formula III is .:. .
.
.. . .
,( R1 3) 9 C R2) n~J ( z) n~BJ ~:
/~K N--N ~.:
- III-l III-2 . ::
., ~.
~`. .
,~ .
., .
., . ,; .
2~ 130 ~R~=~; (R~)r,~; or N--N N--N
" 10 .. ' .
., .
:,`'.' .
` 15 .:
, ~'.' ', '.
~,~ 20 (u,~
.~ N~
. :, `' III-5 ~.`;1 2 5 .~i , . ' ~: .
~`;. :, .. :
.30 X^ is O or S;
t i8 O, 1 or 2;
V is 0, S(O)q, or NR6;
'. Z~ is O or NR6;
:~; R13 is H, halogen, Cl to C6 alkyl, C2 to C9 ;; alko~ycarbonyl, phenyl or phenyl substi-.~ tuted by 1 to 3 ~ubstituents independently selected from W; and .y g is 0, 1 or 2.
.-, , .
'7~i ~
.,~ ., .
.~ ' '- .
, - ,: : '- .: ;. : .,: ` . : : , ::: : , :: ' : : , : . ~ :
2~Q0~3~ ~
:: g Preferred compounds B are compounds A wherein:
Rl is halogen, CN, NO2, OCF2H, OCF3, OCH2CF3, .. 5 OCF2CF2H, CF3 or when m is 2 then Rl may be taken together ~s CH2C(CH3)2O or CF2CF2O to :
:: form a 5 membered ring; .
R2 is H, halogen, CN, NO2, OCH3, OCF2H, OCH2CF3, OCP3, SCH3, SCF2H, SCF3, CF3, OCF2CF2H or . 10 pheno~y: .
R3 and R14 are independently R2 or ~O2R4;
Q is SX, C2 to C4 alko~ycarbonyl, C2 to C4 alkylcarbonyl, C7 to C8 phenylcarbonyl or CHO;
. 15 X is Xl, X2 or X3;
RB is Cl to C4 alkyl, CF3, cyclohexyl, phenyl . optionally substituted with W or benzyl : optionally substituted by W;
. Rg is F, Cl to C22 alkyl, Cl to C6 haloalkyl, ~ 20 phenyl or phenosy optionally substituted b~
:. W; Cl to C22 alkoxy, dimethylamino or Cl to C4 alkoxy substituted with NO2, C2 to C4 alko~y or 1 to 6 halogens;
: m, n or p are independently 1 to 2 and one substituent is in the 4-position and is H~ Cl-C4 alkyl~ CO2R4, C~O)R4 or phenyl ~,'! optionally substituted by (R14)p.
,......................................................................... . .
.j Preferred compounds C are preferred compounds B
-. 30 wherein: .
~t X iS Xl;
; R8 is Cl to C4 alkyl;
i- Rg is Cl to C22 alko~y;
,.J Formula III is III-l or III-2;
`. 35 V is O or CH2; - :~.
. t is l; and .j R13 iS ~
., . :
~'',~ ' . ' .
~ '-. :
. . ~:
,. .. ~
- 2~ Q C 13~
:
,.'. ::. Preferred compounds D are preferred c~mpounds B
5 wherein:
X is X ;
R8 is Cl to C4 alkyl or phenyl optionally ~: substituted with CH3 or Cl; and Rg is Cl to C6 alkyl, Cl to C6 haloalkyl, : 10 dimethylamino or phenyl optionally substituted with CH3 or Cl.
i :
Preferred compounds E are preferred compounds C
. of Formula 1.
; 15 Preferred compounds F are preferred compounds B
of Formula II. :~
Preferred compounds G are preferred compounds B
of Formula III.
~ Specifically preferred are the compounds:
:............ 20 H. methyl 3,4-di-(4-chlorophenyl)-1-l[N- :
tl(ethoxycarbonyl)(l-methylethyl)-amino]thio]-N-t4-(trifluoromethyl)- ~,' ^~1 phenyl]amino]carbonyl]-4,5-dihydro-j~ lH-pyrazole of preferred E;
.. 25 1. N-acetyl-3,4-bis(4-chloropheny)-.~
~ 4,5-dihydro N-[4-(trifluoromethyl) ~ phenyl]-lH-pyrazole-l-carbo~amide of ~.~ preferred F; and , .. .
J. methyl 7-chloro-3,3a,4,S-tetrahydro-~ 30 2-[tN-[tN-methyl-N-toctadecyloxy)--~ carbonyl]amino~thio]-N-[4-(trifluoro-methyl)-phenyl]amino]carbonyl~-2H-benz-.~ [g]indazole-3a-carbo~ylate of preferred ::~ G.
.~ .
' ' . ,.
,; -,. ~... ,, " - .. , . : ,, . ;: . ., . .,. . -, . - . : -- . . . .. ~ - . -.:. , - . , .:- . . :~, : . ... .. . .. ..
.:. . , ,.... . : . , - ~ ~ . , . . . : , , .
f .. .. . . -, . . : -, . , . .. ~ ... .
l:L
etails of the Inven~inn Compounds of FormuIae I, II and III can be prepared by the reaction of a pyr~zoline compound of Formula V, VI or VII with a sulfenyl halide of Formula IV.
(RZ)n{~ ~5y : ITI
( R, ) m~NH
:., .
. . .
. V IV
., :.
; 20 .~ .
.'~
-,' (R2)n 25~kR3)p ~ N~N~ ~ XSY ' I
( RZ ) n~ R3 ~ P ~ 3 ) "
1 Q N~N N~X
x T H ~( Rl ) m ~a~( Rl ) m II .
` ., ,' . .
;'` A J.
~,~ O
.
~, .
wherein .j'!;'' A is a 1, 2 or 3-atom bridge ~omprising O ~o 3 i......................... carbon atoms, 0 to 1 o~ygen atoms, NR6, or .i 35 StO)q, wherein each carbon individually.can be sùbstituted with 1 to 2 substituents- .
selected from 1 to 2 balogen, Cl to C6 alkyl, ., .
':
.1 . , .
.~ , .
,',~, ' , -Z~ 30 C2 to C4 alkoxycarbonyl or phenyl optionally substituted with 1 to 3 substituents independently ~elected from W and one of the carbon atoms can be c~mbined into the group C(O) or C(S); .
H is H, Cl to C6 al~yl, C4 to C7 cycloalkyl alkyl, C3 to C6 cycloalkyl optionally substituted with 1 to 2 halogens or 1 to 2 CH3; Cl to C6 haloalkyl, C2 to C6 alkenyl, C2 to C6 haloalkenyl, C2 to C6 alkynyl, OR7, C2 ':r to C6 alkoxyalkyl, C2 to C6 cyanoalkyl, C3 to C8 alkoxycarbonylalkyl, CO2R4, C(O)R4, C(O)NR4Rs, C(S)NR4Rs, C(S)R4, C(S)~R~, phenyl, phenyl substituted by (R14)p, benzyl, or benzyl substituted with 1 to 3 substituents independently selected from W;
.: J is H, Cl to C4 alkyl or phenyl optionally substituted with W;
: R is H or CH3;
q is 0, 1 or 2;
. R1, R2, R3 and R14 are independently selected / from R4, halogen, CN, N3, SCN, NO2, OR4, SR4, :.~ 25 S(O)Rg~ S(O)2R4, OC(O)Rq~ OS(O)2R4, CO2R4, C(O)R4~ C(O)NR4R5~ S()2NR4R5~ NR4R5, NRSC(O)R4, OC(O)NHR~, NR5C(O)NHR4 and .~
NR5S(O)2R4: or w~en m, n or p is 2, Rl, R2, :-;; R3 or 214 can independently be tahen together ~. 30 as OCH2O, OCH2CH2O or CH2CH2O, to form a ~ or .
-~ 6-membere~ ring, each of which can be independently substituted with 1 to 4 halogen atoms or 1 to 2 methyl groups;
: R4 is selected from H, Cl to C6 alkyl, C3 to C6 cycloalkyl, C3 to C8 alko~ycarbonylalkyl, C3 to C6 alkenyl, C3 to C6 alkynyl, Cl to C6 ` ' ' .
, :
- , . . .
2~ 130 ':
haloalkyl, C3 to C6 haloalkenyl, Cl to C6 alkyl substituted with CN, CO2CH3, CO2CH2CH3, - OCH3~ OCH2CH3~ SCH3, ~CH2CH3 or NO2, or R4 is phenyl or benzyl, ~either optionally substituted with W; or R4 3nd R5 can be taken together as (CH2)4, (CH2)~ or CH2CH2OCH2CH2;
R5 is selected from H, Cl to C4 alkyl, C3 to C4 . .
.: 10 alkenyl, C3 t~ C4 alkynyl or Cl to C4 halo- ~ ~
alkyl; ~ ;
m, D and p are independently 1 to 3;
W is halogen, CN, NO2, Cl to C2 alkyl, Cl to C2 haloalkyl, Cl to C2 alko~Y, Cl to C2 halo ;~ 15 alkoxy, Cl to C2 alkylthio, Cl to C2 halo- :.
alkylthio, Cl to C2 alkylsulfonyl or Cl to C2 hal~alkylsulfonyl;
R6 is H, Cl to C4 alkyl, Cl to C4 haloalkyl, C2 to C4 alkenyl, C2 to C4 haloalkenyl, phenyl .. 20 optionally substituted with W or benzyl optionally substituted with W;
R7 is H, Cl ts C4 alkyl, C2 to C4 alkenyl, C2 to :
C4 alkynyl, C2 to C4 alkylcarbonyl, C2 to C4 ~, alko~ycarbonyl or Cl-C4 alkylsulfonyl;
~; 25 Q is SX, C2 to C22 alko~ycarbonyl, C2 to C22 haloalkoxycarbonyl, C7 to C15 pheno~ycarbonyl ; optionally substituted with 1 to 3 substi- :
tuents selected from W; C7 to C15 phenyl . carbonyl optionally substituted with 1 to 3 j.
~ 30 substituents independently selected from W;
-i C~ to C22 alkyl carbonyl, C2 to C22 haloalkyl carbonyl, CHO, C(O)CO2R5, or C8 to C12 ben- .
. zylo~ycarbonyl optionally substituteD with 1 : to 3 substituents independently ~elected from ., ~ .
., ~ .
..
', . : .
2t~ 3~
W; when Q is other than SX, R3 is other than C~2R4~ C(O)R4~ SO2NR3R4 or CONR4R5;
Y is C5 to C22 alkyl, C2 to C22 haloalkyl, C5 to C22 alkoxyalkyl, C4 to C22 alko~yalkoxyalkyl, C5 to C12 alkylthio, C5 to C12 haloalkylthio, ; C5 to C22 alkylcarbonyl, C5 to C22 haloalkylcarbonyl, C5 to C22 alkoxycarbonyl, . 10 C3 to C22 haloalkoxycarbonyl, or ~X;
Z is C7 to C22 alkyl~ C2 to C22 haloalkyl, C7 to C22 alko~yal~yl, C4 to C22 alko~yalko~yalkyl, C7 to C12 alkylthio, C7 to C12 haloalkylthio, C7 to C22 alkylcarbonyl, C7 to C22 :: 15 haloalkylcarbonyl, C7 to C2~ alko~ycarbonyl, C3 to C~2 haloalkoxycarbonyl or SX;
.
~ 20 X ~s NR8CRg, NR85~)aRg, NR8~ NR8P~ ;
~R9 PI~OR1O NRBR12 Or SR10 ~I - X~ ~ X1 ~8 R~ and R12 are independently Cl to C6 alkyl, ~; Cl to C6 haloalkyl, C3 to C6 cycloalkyl, C4 to . 30 C7 cycloalkylalkyl, phenyl optionally substituted by 1 to 2 substituents selected ` from W, benzyl optionally substituted by 1 to 2 substituents independently selected ~rom W, : phenethyl optionally substituted by 1 to 2 substituents independently selectea from W, C2 `~
to C6 cyanoalkyl, C2 to C6 alko~yalkyl, C3 to .'.. . .
", ~ . ., .. ~' 2~ 30 C8 alkoxycarbonylalkyl, C4 to C8 dialkylaminocarbonylalkyl; or RH and R12 can be - taken together as (CH2)4, (CH2)5 or (CH2~20(CH2)2' Rg is F, Cl to C22 alkyl, C3 to C6 cycloalkyl, C3 to C6 cycloalko~y, C2 to C8 dialkylamino, Cl to C6 haloalkyl, phenyl or pheno~y eithes optionally substituted by 1 to 2 substituents independently selected from W; Cl to C22 . alkoxy, Cl to C4 alkoxy substituted by cyano, nitro, C2 to C4 alko~y, C4 to C8 alko~yalko~y, Cl to C2 alkylthio, C2 to C3 alko~ycarbonyl, C3 to C5 dialkylaminocarbonyl, phenyl or 1 to 6 halogens; or Rg is morpholino, piperidino or . pyrrolidino, l-naphthosy, 2,2-dimethyl-2,3-- dihydrobenzofurano~y-7 or ON~sC~CH3)SCH3; :
. Rlo and Rll are independently Cl to C4 alkyl, C2 to C4 haloalkyl or phenyl optionally i substituted by 1 to 2 substituents ...
independently selected from W: or Rlo and Rll .' can be taken together as (CH2)2, (CH233 or CH2C(CH3)2CH2;
Y~ is S or O; and :
- a is 0 to 2. ~.
., ~' .
. Preferred compounds A are those of Formula I, Il or III wherein: :
-~ 30 Rl, R2, R3 and R14 are independently R4, CO2R4, ~rl halogen, CN, NO2, OR4, SR4, S(O)R4, S(O)2R4 or NR4R5, or when m, n or p is 2; .. :
Rl, ~2~ R3 or R14 can be taken together as OCH2O, x OCH2CH2O or CH2CH2O, each of which can be :y 35 substituted with 1 to 4 halogen ~toms or 1 to 2 ~:
; methyl groups;
~, .
s :~, . , . ~(, . . -- -2~ 13~
R4 is Cl to C2 alkyl, C3 to C4 alkenyl, Cl to C2 haloalkyl, C3 to C4 haloalkenyl or phenyl optionally substituted with halogen;
R5 is H or-Cl to C2 alkyl;
Q is S~, CHO, C2 to C6 alkoxycarbonyl, C2 ~ to C6 haloalko~ycarbonyl, C2 to C6 alkyl-: . carbonyl, C2 to C4 haloalkylcarbonyl, C7 to C10 phenosycarbonyl, C7 to C10 phenylcarbonyl or C8 to ClO benzylo~Y
carbonyl each pheno~y, phenyl ~r benzyl-o~y group optional~y ~ubstituted with 1 ~ to 2 substituents selected from W;
15 X is Xl, X2, X3, X4 or Xs;
- R8 and R12 are independently Cl to C6 alkyl, Cl to C6 haloalkyl, CS to C6 cycloalkyl, ` C3 to C8 alko~ycarbonylalkyl, phenyl, benzyl or phenethyl, each optionally ~ independently substituted with W; or R8 and R12 can be taken together as (CH2)4, (cH2~5 or (CH2)2O(cH2)2;
. R1o and Rll are independently Cl to C3 alkyl ~` or phenyl;
; 25 a is 2; .
. Formula III is .:. .
.
.. . .
,( R1 3) 9 C R2) n~J ( z) n~BJ ~:
/~K N--N ~.:
- III-l III-2 . ::
., ~.
~`. .
,~ .
., .
., . ,; .
2~ 130 ~R~=~; (R~)r,~; or N--N N--N
" 10 .. ' .
., .
:,`'.' .
` 15 .:
, ~'.' ', '.
~,~ 20 (u,~
.~ N~
. :, `' III-5 ~.`;1 2 5 .~i , . ' ~: .
~`;. :, .. :
.30 X^ is O or S;
t i8 O, 1 or 2;
V is 0, S(O)q, or NR6;
'. Z~ is O or NR6;
:~; R13 is H, halogen, Cl to C6 alkyl, C2 to C9 ;; alko~ycarbonyl, phenyl or phenyl substi-.~ tuted by 1 to 3 ~ubstituents independently selected from W; and .y g is 0, 1 or 2.
.-, , .
'7~i ~
.,~ ., .
.~ ' '- .
, - ,: : '- .: ;. : .,: ` . : : , ::: : , :: ' : : , : . ~ :
2~Q0~3~ ~
:: g Preferred compounds B are compounds A wherein:
Rl is halogen, CN, NO2, OCF2H, OCF3, OCH2CF3, .. 5 OCF2CF2H, CF3 or when m is 2 then Rl may be taken together ~s CH2C(CH3)2O or CF2CF2O to :
:: form a 5 membered ring; .
R2 is H, halogen, CN, NO2, OCH3, OCF2H, OCH2CF3, OCP3, SCH3, SCF2H, SCF3, CF3, OCF2CF2H or . 10 pheno~y: .
R3 and R14 are independently R2 or ~O2R4;
Q is SX, C2 to C4 alko~ycarbonyl, C2 to C4 alkylcarbonyl, C7 to C8 phenylcarbonyl or CHO;
. 15 X is Xl, X2 or X3;
RB is Cl to C4 alkyl, CF3, cyclohexyl, phenyl . optionally substituted with W or benzyl : optionally substituted by W;
. Rg is F, Cl to C22 alkyl, Cl to C6 haloalkyl, ~ 20 phenyl or phenosy optionally substituted b~
:. W; Cl to C22 alkoxy, dimethylamino or Cl to C4 alkoxy substituted with NO2, C2 to C4 alko~y or 1 to 6 halogens;
: m, n or p are independently 1 to 2 and one substituent is in the 4-position and is H~ Cl-C4 alkyl~ CO2R4, C~O)R4 or phenyl ~,'! optionally substituted by (R14)p.
,......................................................................... . .
.j Preferred compounds C are preferred compounds B
-. 30 wherein: .
~t X iS Xl;
; R8 is Cl to C4 alkyl;
i- Rg is Cl to C22 alko~y;
,.J Formula III is III-l or III-2;
`. 35 V is O or CH2; - :~.
. t is l; and .j R13 iS ~
., . :
~'',~ ' . ' .
~ '-. :
. . ~:
,. .. ~
- 2~ Q C 13~
:
,.'. ::. Preferred compounds D are preferred c~mpounds B
5 wherein:
X is X ;
R8 is Cl to C4 alkyl or phenyl optionally ~: substituted with CH3 or Cl; and Rg is Cl to C6 alkyl, Cl to C6 haloalkyl, : 10 dimethylamino or phenyl optionally substituted with CH3 or Cl.
i :
Preferred compounds E are preferred compounds C
. of Formula 1.
; 15 Preferred compounds F are preferred compounds B
of Formula II. :~
Preferred compounds G are preferred compounds B
of Formula III.
~ Specifically preferred are the compounds:
:............ 20 H. methyl 3,4-di-(4-chlorophenyl)-1-l[N- :
tl(ethoxycarbonyl)(l-methylethyl)-amino]thio]-N-t4-(trifluoromethyl)- ~,' ^~1 phenyl]amino]carbonyl]-4,5-dihydro-j~ lH-pyrazole of preferred E;
.. 25 1. N-acetyl-3,4-bis(4-chloropheny)-.~
~ 4,5-dihydro N-[4-(trifluoromethyl) ~ phenyl]-lH-pyrazole-l-carbo~amide of ~.~ preferred F; and , .. .
J. methyl 7-chloro-3,3a,4,S-tetrahydro-~ 30 2-[tN-[tN-methyl-N-toctadecyloxy)--~ carbonyl]amino~thio]-N-[4-(trifluoro-methyl)-phenyl]amino]carbonyl~-2H-benz-.~ [g]indazole-3a-carbo~ylate of preferred ::~ G.
.~ .
' ' . ,.
,; -,. ~... ,, " - .. , . : ,, . ;: . ., . .,. . -, . - . : -- . . . .. ~ - . -.:. , - . , .:- . . :~, : . ... .. . .. ..
.:. . , ,.... . : . , - ~ ~ . , . . . : , , .
f .. .. . . -, . . : -, . , . .. ~ ... .
l:L
etails of the Inven~inn Compounds of FormuIae I, II and III can be prepared by the reaction of a pyr~zoline compound of Formula V, VI or VII with a sulfenyl halide of Formula IV.
(RZ)n{~ ~5y : ITI
( R, ) m~NH
:., .
. . .
. V IV
., :.
; 20 .~ .
.'~
-,' (R2)n 25~kR3)p ~ N~N~ ~ XSY ' I
3 U H~ Rl ) m VI IV
, . .
: .
' ,.
5 -.
. ~ ( Ra)~ R3) p ~ XSY II
N,~, o~R1)m VII I~
: 15 ., ' ,~
wherein Y in Formula IV represents a halogen -such as ' 20 chloro, bromo, or iodo.
.;, -- The treatment of V, VI or VII with IV is carried ~,. out by mi~ing the two reagents in the presence of a .};~ base and a solYent. Suitable bases are the tertiary amines such as triethylamine or pyridine. Alkali metal bases such ~s sodium hydride or potassium tert-butoxide or organo lithium bases such as aryl or alkyllithium also can be utilized.
~ Suitable solvents include methylene chloride, -~ 30 tetrahydrofuran or ether. In some cases, the b~se can also be used ~s tbe solvent, e.g., pyridine. In most cases, it is desirable to mi~ compounds of Formula V, VI or VII and the desired base at a low temperature of ; about 5C to -70~C which is held at this. temperature 35 during treatment with the appropriate amount o ;
compounds of Formula IV. The mi~ture is then warmed .j .
.. . .
Z~ Q
to room temperature to complete the reaction.
Cenerally, it is desirable to employ a moderate 5 stoichiometric ex~ess, up to 10% of the base and ~-compounds of For~ula IV relative to compounds of Formula V, VI or VII. Water should be excluded from the reaction mixture by using anhydrous reagents and conducting the treatment in a nitrogen atmosphere.
The product is isolated and purified by conventional techniques as demonstrated in E~ample 1. The pyra-zoline precursors of Formula V, VI, and VII are compounds that can be prepared by methods known to those skilled in the art. The methods of pyrazoline synthesis have been re~ently reviewed by El-Rayyes and Al-Awadi in ~Synthesis" page 1028 to 1042, No~ember 1985.
Compounds of Formula V wherein 8-H can be prepared by the following sequence of reactions as ~0 shown in Scheme 1.
SCHEME I
~,, .
Rx A
tR2)n ~ ~ N~N-~N2 ~ ~ J
VIII IX !~
. ',' .
' ~' : :-Z~}~ 30 ~ .
; IX ~ CR,) ~ NCO ~ V CE~H~
:`
... :
In another embodiment, certain compounds of Formula V wherein B is other than H can be prepared . directly from compounds of Formula V wherein B is H
~. by further treatment with a base and the appropriate;~ type of electrophile as illustreted by Scheme 2.
ScHEME-~
; .
.. ; 1. Base ;
. ?, V ~ V
i~ :
:. (B is H) 2. electrophile (~ is other than H, .'~i phenyl, or substi-tuted phenyl) :i Compounds of Formula V where ~ is also phenyl ~
or substituted phenyl can be prepared by reaction of a .::
substituted ketone of Pormula X with hydrazine ~s .
~ shown in Scheme 3.
: 30 ... .
.;j .
..
.
:`
...... . .
, .:, , .
.. . .
.
. ' ' ' , .
Zi' 1 !~130 . :
~HEME.
5.
..
Rx (I~)n~ ~ H~N-~ ~ ~R~) f~N~
X XI
~X = Cl, E~r, to~yl Dr oth~ laavlng groups) .
.' . .
, 20 .
...
Xl ~ ( R1~ m~NC~ - -~ V :
2 5 ,1.. ~.. :.-... Cl~ 1~ ph~nyl or ~lubstltut~d phenyl) ~ .
. ,. j .
~, 30 For compounds of Formula VI, Grosscurt et al., ' have published the synthesis of 3,4-diphenyl-1-phenyl-~i carbamoyl-2-pyrazolines in Journal o~ Agricultural ~-and ~ood Chemistry, 27:406-409 ~1979). 8imilhr . methods of synthesis are also pre~ented in U.S.
.,. 35 4,633,341. Compounds of Fo~mula VII have been prepared using procedures indicated in PCT -.~ W0 88/05046.
.-~ .
'', '.
- , -2~C~ 13~
Sulfenyl halides of the type XSY (Formula IV) wherein X and Y are as specified in this di6closure are known in the literature. A review article by Kule in Synthesis, 561, (1970) describes the chemistry and preparation of the majority of sulfenyl halides utilized in this invention. The synthesis of N-chlorosulfenylcarbamates was described in U.S.
3,893,6~9. Other sulfenyl halides can be prepared by the general procedures described in these literature e~amples or obvious modifications thereof.
Compounds of Formula I (Q is other than SX) are synthesized from compounds of Formula VI.
Reaction of compounds of Formula VI in the presence of an acid acceptor with electrophilic carbonyl-containing reagents results in substitution on nitrogen. Strong bases known to deprotonate ureas - such as potassium t-butoxide, potassium hydride and sodium hydride are the preferred acid acceptors in the process. Suitable electrophiles include, but are not restricted to , acyl halides, acid anhydrides, carbonates, and chloroformates. The reaction sequence is normally run in the temperature range of -10 to 25C, but can be run at temperatures as high as 110C or as low as -50C in certain cases.
Solvents which are not deprotonated under the conditions of the reaction such as tetrahydrofuran, dimethylformamide, dimethoxyethane, and diethyl ether ~ 30 ": :
;
.'' . :
:
.~, . , . : . ~ . -- , . ~: , , , . ~:
Z.~ 130 are preferred. The electrophiles used in this process are well kn~wn to those skilled in the art and are generally commercially svailable.
Acid - Acceptor VI ~ QX ~ II
~ wherein: -; QX is selected from a~yl halides, chloroformates a~d acid anhydrides.
, . . .
The following Examples illustrate the in~ention.
.: .
Example l i~-3,3a,4,5-Tetrahydro-3a-metho~ycarbonyl-N-[4-(trifluoromethyl)pheny]-N-tN'-~l-methyl-; ethyl)-N~-(ethoxycarbonyl)aminosulfenyl]-2H-benzralindazole-2-carboxamide .
` Step A: 3,3a,4,5-Tetrahydro-N-14-(trifluoromethyl)-phenyl]-2H-benz[g]indazole-2-carbo~amide ::
-~-; A mi~ture of l0.0 9 of a-tetralone, 2.0 9 of paraformaldehyde, 6.5 9 of dimethylamine hydrochloride and 1.75 ml of conc. HCl in 20 ml of ethanol was heated at reflu~ for 24 h, Gooled to room temperature ~nd then partitioned between ether and water. The aqueous e~tracts were made basic with lN
'~ ~gueous NaOH and e~tracted with ether. The ether extracts were dried over magnesium sulfate ~nd concentrated to 12.3 9 of a yellow oil. The residual ` oil was dissolved in 40 ml of n-propyl alcohol, c~mbined with 6.7 ml f hydra&ine hydrate and h ated ., . ' Z~JIJ~1 30 1~
at reflu~ for 1 h. The reaction mi~ture was then concentrated under vacuum, partitioned between 5~
S aqueous NaHCO3 and methylene chloride and dried over magnesium sulfate. To the methylene chloride extracts were added 12.5 9 of 4-trifluoro-methylphenyl isocyanate and the mi~ture was then re-fluxed one hour, cooled to room temper3ture and con-~ 10 centrated to 26.1 9 of a brown oil. Chromatography - on silica gel followed by trituration with ether afforded 11.78 9 of the title compound as a tan powder, m.p. 149-151C.
H NMR ~CDC13), ~ 1.9 (m,lH), 2.4 (m,lH), 3.0 Sm, 2H), 3.5 (m,2H), 4.4 (m,lH), 7.3 (m,3H), 7.58 (d,2H), 7.65 (d,2H), 8.0 (d,2H), 8.3 (bs,lH).
Step B: 3,3a,4,S-tetrahydro-3a-metho~ycarbonyl-N-[9'-(trifluoromethyl)phenyl]-2H-benz[g]-indazole-2-carboxamide . . .
To a solution of 0.9 ml of diisopropylamine ,~ in 10 ml of THF, at -78C, was added 2.3 ml of 2.5 M
n-butyl lithium in hexane and the mi~ture was stirred for 5 mins. To this olution was added a solution of 1.0 9 of the title compound of Step A in 5 ml of THF. The reactio~ was warmed to 0C, recooled to - -78C and then 0.75 ml of methyl chloroformate was added. The reaction mi~ture was then stirred for 24 h, with gradual warming to room.temperature, quenched with 0.5 ml of glacial acetic acid, and poured into a 5% solution o aqueous NaHCO3. The mi~ture was -~ e~tracted with chloroform, dried over magnesium sulfate and concentrated. Chromatograph~ on ~ilica.
gel with 30% ethyl acetate hexane afforded 0.25 9 of the title compound, m.p. 177 to 180C.
.~ .
.' ` . .
.. . .
2~13(1'130 .' 19 ~.
lH NMR (CDC13), 6 2.1 (m,lH), 2.7 (m,lH), 3.0 (m,2H), ; 3.71 (s,3H), 3.76 (d,lH), ~.58 (d,lH), 7.3 (m,3H), 7.~7 (d,2H), 7.6Ç (d,2H), 8.0 (d,lH), 8.22 (s,lH).
Step C: Ethyl (l-methylethyl)carbamate . , To a solution of ethyl chloroformate (21.7 9, 0.2 mol~ in 200 ml ether cooled to 0C was added dropwise 35.7 ml of isopropylamine with stirring and cooling. After complete addition of t~e amine, the reaction mixture was stirred at room temperature for an additional 0.5 hour. The reaction mixture was filtered, and the ether solution was washed with ` water, and dried over magnesium sulfate. Evapora-tion of the ether and distillation of the residue in .~ a Kugelrohr apparatus resulted in 22. 6 9 of the title compound ~.p.: 50-66DC (bath temperature) at l.S mm Hg.
.
Step D: Ethyl (chlorosulfenyl)(l-methyl-ethyl)carbamate .; .
To a solution of ethyl (l-methylethyl)-- carbamate (13.1 g, 0.1 mol) in 100 ml methylene ~ chloride cooled to 0C was added sulfur dichloride - (11.3 9, 0.11 mol) in one portion. While maintaining -~i the temperature of the mixture at 0C, pyridine (8.7 30 9, 0.11 mol) was added dropwise over eleven minutes; -~
After complete addition of the pyridine the temperature was allowed to rise to room temperature ,j,!
snd stirring was continued for additional 1.5 hours.
The mixture was let ~tand overnight. Methylene : 35 chloride was evaporated under vacuum and 100 ml hexane was added. Filteration of the pyridine ;
~' ' -.
. . :
ZS}f ~130 hydrochloride and evaporation of hexane resulted in an orange oil which was distilled in a Kugelrohr appara~us to give 12.5 g of the title compound Bp:
64-80 (bath temper~ture) at 1.4 mm Hg.
Step E: 3,3a,4,5-Tetrahydro-3a-metho~ycarbonyl-N-[4-(trifluoromethyl)phenyl]-N-[N'-(l-methyl-ethyl)-N'-(etho~cycarbonyl)aminosulfenyli-2H-benz[g]indazole-2-carbo~amide , To a solution of the title compound of Step (2.0 9, 4.8 mmol) in 50 ml methylene chloride cooled to 0CC was added triethylamine (1.0 9, 0.01 mol~ and ethyl (chlorosulfenyl)(l-methylethyl)carbamate from Step D (1.4 9, 7.7 mmol). The misture was allowed to warm to room temperature and stirred for one hour.
; The crude mi~ture was purified by silica column . 20 chromatography using ether-hexane (1:2) as eluent.
- The title compound (2.38 9) was obtained in about 90%
- purity (mp: 130-134). Extraction of the product : with ether-hexane (2:1) gave 1.8 9 of highly pure '. material mp: 139-140C.
lH NMR (CDC13); ~ 0.92 (t,3H), 1.26 (d,3H), 1-35 (d,3H), 1.95 (m,lH), 2.7 (m,lH), 2.95 (m,2H), 3.67 (s,3H), 3.8 (m,3H), 4.5 (m,2H), 7.2 (m,3H), 7.45 ; (d,3H), 7.65 (d,2H~.
E~amPle 2 3,3a,4,5-Tetrahydro-3a-metho~ycarbonyl-N-:' 14-(trifluoromethYl)Phenyl]-N-~l-methyl-propo~ylcarbonylsulfenyl)-2H-benz[g]-_ indazole-2-carboxamide.
~; 35 Step A: (l-methylpropoxycarbonyl)sulfenyl chloride ., ' ~' .
... .. , .......... . ..... .. : . ,,, . -: .
:: . .. ~ ,: . : . . . ~ . . , :,. ,. . . . -Z~3~3C~
Chlorocarbonylsulfenyl chloride (13.1 ~, 0.1 m~l) was mixed with 2-butanol (6.7 9, 0.09 mol3 and wa~med to about 35 to 40C for one hour. Distil-lation resulted in the title compound (5.93 9) ~p.
70C/0.8 mm Hg. NMR spectrum was ~onsistent with the structure.
Step B: 3,3a,4,~-Tetrahydro-3a-metho~ycarbonyl-N-[4-(trifluoromethyl)phenyl]-N-~l-methyl-propo~ycarbonylsulfeny~)-2H-benz[g]indazole-2-carboxamide.
To a solution of the title sompound of Step B
-~ (Example 1) (0.4 9, 0.96 mmol) in 5 ml methylene chloride was added triethylamine (0.12 9) and cooled to 0C. To this solution was added (l-methylpropoxy-car~onyl)sulfenyl chloride (Step A) (0.2 9, 0.0012 mol). The mixture was stirred at room temperature for one hour. At this stage thin layer chromatography indicated only partial conversion, therefor, addition- al amounts of (l-methylpro-poxycarbonyl)~ulfenyl chloride (0.2 93 and triethylamine (0.12 9) was added and the mi~ture was let stand overnight. The reaction mi~ture was subjected to silica gel column chromatography using hexane-ether (7:1) as eluent. The title compound was `-obtained (0.22 9) in high purity; m.p.: 125-126C.
lH NMR (CDC13): ~ 0.9 ~m,3H), 1.3 ~m,3H), 1.6 (m,2H), 1.9 ~m,lH), 2.B (m,3H), 3.67 (s,3H), 3.8 (d,lH), 4.5 (d,lH), 5.0 (m,lH), 7.05 ~m,3H), 7.25 (m,lH), 7.5 (d,2H), 7.57 (d,2H).
'.'-. '.
.
: ':
. .
~, : . . . . . . . . . .
,;,. . . . . . , ... . . . ~ ` ~ . . . . . :
.,. . - .
Z~130 . ~ ~ ..
3,3a,4,5-Tetrahydro-3a-methoxycarbonyl-N-[4-(trifluoromethyl)phenyl~-N- (dibutyl amino-sulfenyl)-2H-benzrglind~zole-2-carbo~ami~e Step A: N,N'-bis-(dibutylamino)disulfide To a solution of dibutylamine (5Z g, 0.4 mol) in 200 ml hexane cooled to 0C was added ~ulfur mono-chloride (13.5 9, 0.1 mol) dropwise with stirring over a period of 20 minutes. The rea~tion mixture was warmed up to room temperature and stirring was continued for 30 minutes. The reaction miature was filtered and he~ane was evaporated to yield 30.1 9 of the title compound.
Step B: Dibutylaminosulfenylchloride To a solution of N,N~-bis-(dibutylamino)disul-`~ fide (13.2 g, 0.05 mol) in 12 ml carbontetrachloride was added. Sulfuryl chloride ~6.75 9, 0.05 mol) was added dropwise at ambient temperature. Then heated to about 60C for 10 minutes, and distilled to give ; the title compound (7.55 9) as a yellow liquid. Bp:
`~ 80-87C at 0.6 mm Hg.
'.'' Step C: 3,3a,4,5-Tetrahydro-3a-metho~ycarbonyl-N-14-, 30 (trifluoromethyl)phenyl~-N-(dibutylamino-sulfenyl)-2H-benz[g]indazole-2-earbosamide.
. :
To a solution of the title compound of Step (Example 1) (0.4 9, 0.96 mmol) in B ml methylene chloride cooled to 0C was added triethyla~ine (0.15 9) and dibutylaminosulfenylchloride (0.2 9~.
.. ..
.. .
., - .. . . ...
.. . ,, : . . . ... . .
2;1~J(~130 The reaction mixture was warmea to room temperature and stirred for one hour. l`he mi~ture was subjected to silica gel column chromatography using hexane-ether (6:1) as the eluent. The title compound was obtained (0.24 g) in high purity.
H NMR (CDC13): ~ 0.7 to 1.7 ~m,14H), 1.9 (m,lH), 2.6 to 3.1 (m,7H), 3.67 (s,3H), 3.75 (d,lH), 4.45 (d,lH), 7.1 (m,3H), 7.25 (m,lH), 7.4 (d,2H), 7.6 (d,2H).
Esample 9 7-Chloro-3,3a,4,5-tetrahydro-3a-methoxy-carbonyl-N-[4-(trifluoromethyl)phenyl]-N-: -[N'-(methyl)-N'-(hexoxycarbonyl)amino-; sulfenyll-2H-benzralindazole-2-carbo~amide ;.~ "
Step A: ((2-(3-chlorophenyl)ethyl)methanesulfonate To a 0C solution of 30.0 g of 3-chloro-; phenethyl alcohol and 15.3 ml of methane sulfonyl chloride in 150 ml of THF was added, dropwise, a solution of 2B.0 ml of triethylamine in 50 ml of THF. The reaction was warmed to room temperature, stirred overnight, and then filtered. The filtrate was partitioned between aqueous sodium bicarbonate and ether. The organic extracts were then dried over ` magnesium sulfate, filtered and concentrated under 3Q reduced pressure to afford 45.93 9 of a clear, colorless oil.
:: .
Step B: 3-chlorobenzenebutanoic acid ~
. .
To a mixture of 8.0 g of 60~ ~odium hydride in 300 ml of THF, under N2, was added dropwise a ; solution of 31.0 ml of diethyl malonate in 50 ml of ., ' ;~ ' ;
", .~
.
Z~3~?13~
THF. Upon complete addition of the diethyl malonate, a pale yellow homogenous solution was obtained. To this was added a solution of 45.93 9 of the sulfonate from Step A and the mixture was then heated at reflu~
` overnight. The reaction was then cooled to room temperature, poured into 400 ml of lN HCl, and e~tracted with ether. The ether extracts were dried over magnesium sulfate, filtered and concentrated under reduced pressure to afford 68.9 g of a yellow oil. The crude oil was dissolved in 400 ml of methanol, 100 ml of H2O and 40 ml of 50~ aqueous NaOH. The reaction was stirred overnight and the methanol was then removed at reduced pressure. The crude residue was partitioned between H2O and ether, the aqueous extracts were acidified with concentrated HCl and then e~tracted several times with ether. The ether e~tracts were dried over maqne- sium sulfate, filtered and concentrated to afford 51.7 9 of a yellow oil. The crude residue was dissolved in 200 ; ml of toluene and heated at reflux for 4 days under N2 to effect decarbo~ylation. After this time toluene was removed by concentration at reduced pressure to afford 35.72 9 of a yellow oil. lH NMR
; analysis of the crude product was consistent with 3-chlorobenzene- butenoic acid of purity estimated to be 80%. The crude product was used without further purification directly in the ne~t step.
-` 30 Step C: 6-chloro-3,4-dihydrG-1(2H)-naphthalenone ` A mi2ture of 35.72 of the produc~ from Step B
~nd 50 ml of thionyl chloride was heated-at reflus for 2 hours and then stirred at room temperature for 18 hours. After this time thionyl chloride was .
- . , . ~ . . , : ~.: : . - .
, ..
removed at reduced pressure and the product was dissolved in carbon tetrachloride and concentrated at reduced pressure The residue was dissolved in 150 ml of dichloroethane cooled to 0C and 28 g of aluminum chloride was added portionwise over about 1 hr in approximately 3 9 portions. After ~tirring for 3 hrs the reaction was poured over a mixture of ice/lN HCl and extracted three times with methylene chloride. The organic extracts were dried over ` magnesium sulfate and concentrated to appro~imately 30 9 of a brown oil. Chromatography on silica gel with 1~ ethyl acetate/hexane afforded 17.B3 g of 6-chloro-3,4-dihydro-1(2H)-naphthalenone as a brown oil. lH NMR was consistent with the structure.
~ Step D: 7-chloro-3,3a,4-5-tetrahydro-N-[4-(tri-'!`: fluoromethyl)phenyl]-2H-benz[g~-indazole-Z0 2-carboxamide : .
A mi~ture of 6-chloro-3,4-dihydro-1(2H)-naphthalenone (Step C), 2.5 9 of dimethylamine hydrochloride, 1.0 g of paraformaldehyde, 0.7 ml of concentrated HCl and 15 ml of ethanol was combined and heated at reflux for 18 hrs. ~he reaction was then concentrated at re- duced pressure and partitioned between H2O and ether. The aque~us extracts were made baic with lN NaOH and then extracted three times with ether. The ether e~tracts ` were dried over magnesium sulfate and concentrated to 4.64 9 of a ~ellow oil. This compound was dissolved in 25 ml of ethanol and 1.5 ml of hydrazine hydrate was added followed by S to 6 drops of 50~ 80dium hydro~ide. The reaction was ~hen heated at reflux, under N2, for 2 to 3 hrs after which time it was cooled and most of the ethanol was removed by ., . .
. . . - : - -. .
Zl" t~-130 concentration at reduced pressure. The crude residue was partitioned between 6aturated aqueous ~odium bicarbonate end methylene chloride. The methylene chloride e~tracts were dried over magnesium sulfate and filtered. The methylene chloride e~tracts were then combined with 3.5 g of 4-trifluoromethylphenyl isocyanate and stirred under N2 overnight. The reaction was then concentrated and the crude residue triturated with ether to afford 3.35 9 of the title compound as a white powder, m.p. 196 to 199C.
lH NMR (CDC13 9 ~ 1. 9 (m, lH), 2 . 2 (m, lH), 3 . O (m, 2H), 3.5 (m,2H), 4.43 (m,lH), 7.24 (m,2H), 7.55 (d,2H), 7.67 (d,2H), 7.92 (d,lH~, 8.20 (s,lH).
. .
Step E: 7-chloro-3,3a,4,5-tetrahydro-3a-methoxy-carbonyl-N-[4-(trifluoromethyl)phenyl]-2H-benz[g]indazole-2-carboxamide A solution of 50 ml of THF and 6.7 ml of - diisopropylamine was cooled under N2 to -78C and then 17.5 ml of 2.5 M n-butyllithium in hexane was ; added. After 5 min, a solution of 7.B g of the title .~ 25 compound of Step D in 15 ml of THF was added dropwise and the dark red solution that formed was stirred at -78C for an additiGnal 15 min. After this time a solution of 4.6 ml of methyl chloroformate in 10 ml of THF was added dropwise and the red color dissipated rapidly. The reaction was warmed to room temperature and after 1 hr guenched with 5% aqueouis sodium bicarbonate. The reaction mi~ture was partitioned between ether and 5% aqueous ~odium bicarbonate. The ether e~tracts were dr~ed o~er magnesium sulfate and concentrated to 14.1 9 of a yellou oily solid. The crude product uas triturated :~
':
. . ., , .: : . . - : ~ .
2i}~ 3~
with ether and the resulting white precipitate was filtered and dried to afford 5.56 9 of the title compound as a whi~e solid, m.p. 234 to 236C.
. 1H NMR(CDC13) 6 2.1 (m,lH), 2.7~ (m,lH), 2.95 (m,2H), 3.71 (s,3H), 3.75 (d,lH, Jo6Hz), 4.59 (d,lH, J~6Hz), 7.25 (m,2H), 7.57 (d,2H), 7.66 (d,2H), 7.94 (d,lH), 8.1B (d,lH).
Step F: 7-chloro-3,3a,4,5-tetrahydro-3a-methoxy-,~ carbonyl-N-14-(trifluoromethyl)phenyl]-N-[N'-(methyl)-~'-(hexoxycarbonyl)amino-sulfenyl]-2H-benz[g]indazole-2-carboxamide To a suspension of the title compound of Step E above (2.2 g, 0.005 mol) in 25 ml methylene chloride cooled to 0C was added triethylamine (1.0 g) and hexyl (chlorosulfenyl)(methyl)carbamate, (prepared in a manner similar to Example 1, Step D), ~ (2.5 9 75% pure) dropwise at 0C. The mixture was - stirred at room temperature for additional one hour.
:~ The reaction mixture was concentrated under high vacuum and subjected to silica gel column chromatography using hexane-ether (1:1) as an eluent. The title compound (2.5 9) was obtained, melting point 128-129C in high purity.
H NMR (CDC13) ~ O.B7 (t,3H), 1.18 (m,8H), 1.9(m,1H), ` 2.B (m,3H), 3.5 (s,3H), 3.66 (s,3H), 3.7 (m,3H), 4.5 - 30 (d,lH), 7.05 (m,3H), 7.35 (d,2H), 7.6 td,2H).
~sing the procedures described in Examples 1 to 4 with o~vious modifications, the compsund~ -exemplified in E~amples 5 to 28 were prepared.
,' . . .
, ''~
.
. :. ... -, . . , , . :, " , , . . .. ;.,: . ., . -. : .- . . ., ~ . . .. .
, . , .: , . . : ~ .
Z~ 3~
~blç A
' R~O~CH3 '. C =~
. C~3 ~N-S-Z
.~ ' .
Example R2 Z m.p.-C lH NMR (~ i~ ppm) : 20 ln CDC13 . .
H NtCH3)CtO)OC4H9 134 1.0(t,3H), 1.2(m,4H), - l.9(m,1H), 2.6-3(m,3B), ~ 3.5(~,3H), 3.66(6,3H), ; 25 3.7(m,2H), 3.75(d,1H), 4.45(d,1H),7.1(m,3H), ` 7.25(m,lH), 7.35(d,2H), ;1 7,6(d,2H).
6 H N(CN3)C(O)OC2H5 121-123 0.88(t,3H), l.9(m,1H), 3C 2.6-3(m,3H), 3.5(s.3H), 3.66 ~,3H), 3.8(m,3H), 4.47(d,1H), 7.11(m,3H), , 7.25 tm,lN), 7.35(d,2H), 7.6~d,2H).
.1 ~ . .
.
!~ .
`, :"
~'.
:f .
.
;: ;
; Example R2 Z m.p.-C lH NMR (6 ~n ppm) -:
~ ~ CDC 13 7 6-F N(CH3)C(O)OC4H9 120 0.83tt,3H), 1.2(m,4H), l.B5(m,1H), 2.7(m,2H),';
3.0(m,1N), 3.5(c,3H), 3.66(e,3H), 3.75(m,3H), ; 4.5(d,1H), 7.0(m,3H), 7.35(~,2H), 7.6(d,3H).
~; 8 H N(CH3~C(O)~cy~loC6H11 175-176 0.6-1.7(m,10H), l.9(m,1H), 2.6-3.0(m,3H), 3.51(s,3H), ~ 15 3.65(s,3H), 3.75(d,1H), : 4.35(m,1~), 4.45 (d,lH), 7.1(m,3H), 7.25(m,1H), ~^ 7.35(d,2H), 7.6(d,2H).
; 9 H N(cH3)c(c)oc8Hl71~4-145 0.88(t,3H), 1.21(m,12H), `~ 20 l.9(m,1H), 2.7(m~1H), 2.9~m,2H), 3.5(m,3H), 3.65(m,3H), 3.75(m,3H), 4.5(d,1H), 7.1(m,3H), ~ 7.25(m,1H), 7.35(d,2H), , '~ 25 7.6 ( d,2H ) .
( 10 ~ N(CH3)C(O)OcloH2l 76-780.88(t,3H), 1.25(m,16H).
-~ l.9~m,1H), 2.7(m,1H), -2.9(m,2H), 3~5(s,3H), , - 3.66(s,3H), 3.75~m 3H), ,~ . , ~ 30 4.5(d,1H), 7.15(m,3H), s~ 7.25(m,1H), 7.35(d,2H), 7.6 (d,2H).
.
~'' , ,',', ' .' :;~ .
, i. , : . . - - : . , . . ~ - . ~ . . .
~ t~3V .:
Example R2 z m.p.-C lB ~MR (6 in ppm) ~ p CDC13 11 6-F N-lCH(CN3~2~C(O)OC2H5 143.5 O.91(t,3H), 1.27(d,3H), 1.35~d,3H), l.9(m,lH), 2.75(m,2H), 3.05~m,1H), 0 3.67(s,3H), 3.75~m,3H), 4.5(m,2H), 7.25(m,3H), 7.45(d,2H), 7.6(d,2B).
12 H N(cH3)c(o)ocl2H25 0.88(t,3H), 1.26(m,20H), l.9(m,1H~, 2.7(m,1H), 2.9(m,2H), 3.5(~,3H), 3.66(~,3H1, 3.75(m,3H), 4.5(d,lH), 7.1(m,3H), ~- 7.25(m,lH), 7.35(d,2H), 7.6(d,2H).
13 H N(CH3)c(O)~c6Hl3 0?88(t,3H), 1.26(m,8Hj, l.9(m,1H), 2.7(m,1H), 2.9(m,2H), 3.51(~,3H), 3.66(6,3H), 3.75(m,3H), 4.5(d,2H), 7.1(m,3H), 7.25(m,1H), 7.35(d,2H), . 7.6(d,2H).
14 7-Cl C(0)0-6ec-C4Hg 132 0.88(t,3H), 1.3(m,3H), ; 1.6(m,2H), l.9(m,1H), ~ 2.6-3.0(m.3N). 3.88(s,3H), f,` 30 3.8(d.1H), 4.5(d,1H), S.O(m,lH), 7.0~m,3H), 7.35(d,2H~, 7.6~d,2H).
15 7-Cl N~ICH(CH3)2]C()C2Hs 152 Oo9~t~3N)~ 1.26(d,3H3, 1.35~,3H), 1.9(m,1H), 2.7(m,1H), 2.9(m,2H), 3.67( ,3H), 3.8(m,3H), 4.5(m,2H~, 7.14(m,2H), 7.4(m,3H), 7.6(d,2A).
.~ , :
,, ' :
r ~
2~0(~130 ' E~ample R2 Z m.p.-C lN NMR (~ in ppm) S ln CDC13 : :.
16 7-Cl N(CH3)C(O)OC2Hs ~ 0.88(t,3H), 1.9~m,1H), 2.65(m,1H), 2.9(m,2H), 3.49(c,3H), 3.66(~,3H), 3.B(m,3H), 4.5(d,1H), 7.07(m, 3H), 7.35(d,2H), 7.6(d,2H).
17 7-Cl N(cH3)c(o)oc8Hl7 103-106 0.88(t,3H), 1.23(m,12H), l.9(m,lH), 2.65(m,lH), 2.85(m,2H), 3.5(c,3H), 3.66(s,3H), 3.75(m,3H), .45(d,lH), 7.05(m,3H), , 7.35(d,2H), 7.6(~,2H).
`~ la 6-F C(O)O-sec-C4H9 125-126 O.9(m,3H), 1.3(m,5H), - 20 l.9(m,1H), 2.75(m,2H), 3.0(m,1H), 3.7(6,3H), . ., 3.8(d,1H), 4.5(d,1H), ~ ..
, . .
: .
' ,.
5 -.
. ~ ( Ra)~ R3) p ~ XSY II
N,~, o~R1)m VII I~
: 15 ., ' ,~
wherein Y in Formula IV represents a halogen -such as ' 20 chloro, bromo, or iodo.
.;, -- The treatment of V, VI or VII with IV is carried ~,. out by mi~ing the two reagents in the presence of a .};~ base and a solYent. Suitable bases are the tertiary amines such as triethylamine or pyridine. Alkali metal bases such ~s sodium hydride or potassium tert-butoxide or organo lithium bases such as aryl or alkyllithium also can be utilized.
~ Suitable solvents include methylene chloride, -~ 30 tetrahydrofuran or ether. In some cases, the b~se can also be used ~s tbe solvent, e.g., pyridine. In most cases, it is desirable to mi~ compounds of Formula V, VI or VII and the desired base at a low temperature of ; about 5C to -70~C which is held at this. temperature 35 during treatment with the appropriate amount o ;
compounds of Formula IV. The mi~ture is then warmed .j .
.. . .
Z~ Q
to room temperature to complete the reaction.
Cenerally, it is desirable to employ a moderate 5 stoichiometric ex~ess, up to 10% of the base and ~-compounds of For~ula IV relative to compounds of Formula V, VI or VII. Water should be excluded from the reaction mixture by using anhydrous reagents and conducting the treatment in a nitrogen atmosphere.
The product is isolated and purified by conventional techniques as demonstrated in E~ample 1. The pyra-zoline precursors of Formula V, VI, and VII are compounds that can be prepared by methods known to those skilled in the art. The methods of pyrazoline synthesis have been re~ently reviewed by El-Rayyes and Al-Awadi in ~Synthesis" page 1028 to 1042, No~ember 1985.
Compounds of Formula V wherein 8-H can be prepared by the following sequence of reactions as ~0 shown in Scheme 1.
SCHEME I
~,, .
Rx A
tR2)n ~ ~ N~N-~N2 ~ ~ J
VIII IX !~
. ',' .
' ~' : :-Z~}~ 30 ~ .
; IX ~ CR,) ~ NCO ~ V CE~H~
:`
... :
In another embodiment, certain compounds of Formula V wherein B is other than H can be prepared . directly from compounds of Formula V wherein B is H
~. by further treatment with a base and the appropriate;~ type of electrophile as illustreted by Scheme 2.
ScHEME-~
; .
.. ; 1. Base ;
. ?, V ~ V
i~ :
:. (B is H) 2. electrophile (~ is other than H, .'~i phenyl, or substi-tuted phenyl) :i Compounds of Formula V where ~ is also phenyl ~
or substituted phenyl can be prepared by reaction of a .::
substituted ketone of Pormula X with hydrazine ~s .
~ shown in Scheme 3.
: 30 ... .
.;j .
..
.
:`
...... . .
, .:, , .
.. . .
.
. ' ' ' , .
Zi' 1 !~130 . :
~HEME.
5.
..
Rx (I~)n~ ~ H~N-~ ~ ~R~) f~N~
X XI
~X = Cl, E~r, to~yl Dr oth~ laavlng groups) .
.' . .
, 20 .
...
Xl ~ ( R1~ m~NC~ - -~ V :
2 5 ,1.. ~.. :.-... Cl~ 1~ ph~nyl or ~lubstltut~d phenyl) ~ .
. ,. j .
~, 30 For compounds of Formula VI, Grosscurt et al., ' have published the synthesis of 3,4-diphenyl-1-phenyl-~i carbamoyl-2-pyrazolines in Journal o~ Agricultural ~-and ~ood Chemistry, 27:406-409 ~1979). 8imilhr . methods of synthesis are also pre~ented in U.S.
.,. 35 4,633,341. Compounds of Fo~mula VII have been prepared using procedures indicated in PCT -.~ W0 88/05046.
.-~ .
'', '.
- , -2~C~ 13~
Sulfenyl halides of the type XSY (Formula IV) wherein X and Y are as specified in this di6closure are known in the literature. A review article by Kule in Synthesis, 561, (1970) describes the chemistry and preparation of the majority of sulfenyl halides utilized in this invention. The synthesis of N-chlorosulfenylcarbamates was described in U.S.
3,893,6~9. Other sulfenyl halides can be prepared by the general procedures described in these literature e~amples or obvious modifications thereof.
Compounds of Formula I (Q is other than SX) are synthesized from compounds of Formula VI.
Reaction of compounds of Formula VI in the presence of an acid acceptor with electrophilic carbonyl-containing reagents results in substitution on nitrogen. Strong bases known to deprotonate ureas - such as potassium t-butoxide, potassium hydride and sodium hydride are the preferred acid acceptors in the process. Suitable electrophiles include, but are not restricted to , acyl halides, acid anhydrides, carbonates, and chloroformates. The reaction sequence is normally run in the temperature range of -10 to 25C, but can be run at temperatures as high as 110C or as low as -50C in certain cases.
Solvents which are not deprotonated under the conditions of the reaction such as tetrahydrofuran, dimethylformamide, dimethoxyethane, and diethyl ether ~ 30 ": :
;
.'' . :
:
.~, . , . : . ~ . -- , . ~: , , , . ~:
Z.~ 130 are preferred. The electrophiles used in this process are well kn~wn to those skilled in the art and are generally commercially svailable.
Acid - Acceptor VI ~ QX ~ II
~ wherein: -; QX is selected from a~yl halides, chloroformates a~d acid anhydrides.
, . . .
The following Examples illustrate the in~ention.
.: .
Example l i~-3,3a,4,5-Tetrahydro-3a-metho~ycarbonyl-N-[4-(trifluoromethyl)pheny]-N-tN'-~l-methyl-; ethyl)-N~-(ethoxycarbonyl)aminosulfenyl]-2H-benzralindazole-2-carboxamide .
` Step A: 3,3a,4,5-Tetrahydro-N-14-(trifluoromethyl)-phenyl]-2H-benz[g]indazole-2-carbo~amide ::
-~-; A mi~ture of l0.0 9 of a-tetralone, 2.0 9 of paraformaldehyde, 6.5 9 of dimethylamine hydrochloride and 1.75 ml of conc. HCl in 20 ml of ethanol was heated at reflu~ for 24 h, Gooled to room temperature ~nd then partitioned between ether and water. The aqueous e~tracts were made basic with lN
'~ ~gueous NaOH and e~tracted with ether. The ether extracts were dried over magnesium sulfate ~nd concentrated to 12.3 9 of a yellow oil. The residual ` oil was dissolved in 40 ml of n-propyl alcohol, c~mbined with 6.7 ml f hydra&ine hydrate and h ated ., . ' Z~JIJ~1 30 1~
at reflu~ for 1 h. The reaction mi~ture was then concentrated under vacuum, partitioned between 5~
S aqueous NaHCO3 and methylene chloride and dried over magnesium sulfate. To the methylene chloride extracts were added 12.5 9 of 4-trifluoro-methylphenyl isocyanate and the mi~ture was then re-fluxed one hour, cooled to room temper3ture and con-~ 10 centrated to 26.1 9 of a brown oil. Chromatography - on silica gel followed by trituration with ether afforded 11.78 9 of the title compound as a tan powder, m.p. 149-151C.
H NMR ~CDC13), ~ 1.9 (m,lH), 2.4 (m,lH), 3.0 Sm, 2H), 3.5 (m,2H), 4.4 (m,lH), 7.3 (m,3H), 7.58 (d,2H), 7.65 (d,2H), 8.0 (d,2H), 8.3 (bs,lH).
Step B: 3,3a,4,S-tetrahydro-3a-metho~ycarbonyl-N-[9'-(trifluoromethyl)phenyl]-2H-benz[g]-indazole-2-carboxamide . . .
To a solution of 0.9 ml of diisopropylamine ,~ in 10 ml of THF, at -78C, was added 2.3 ml of 2.5 M
n-butyl lithium in hexane and the mi~ture was stirred for 5 mins. To this olution was added a solution of 1.0 9 of the title compound of Step A in 5 ml of THF. The reactio~ was warmed to 0C, recooled to - -78C and then 0.75 ml of methyl chloroformate was added. The reaction mi~ture was then stirred for 24 h, with gradual warming to room.temperature, quenched with 0.5 ml of glacial acetic acid, and poured into a 5% solution o aqueous NaHCO3. The mi~ture was -~ e~tracted with chloroform, dried over magnesium sulfate and concentrated. Chromatograph~ on ~ilica.
gel with 30% ethyl acetate hexane afforded 0.25 9 of the title compound, m.p. 177 to 180C.
.~ .
.' ` . .
.. . .
2~13(1'130 .' 19 ~.
lH NMR (CDC13), 6 2.1 (m,lH), 2.7 (m,lH), 3.0 (m,2H), ; 3.71 (s,3H), 3.76 (d,lH), ~.58 (d,lH), 7.3 (m,3H), 7.~7 (d,2H), 7.6Ç (d,2H), 8.0 (d,lH), 8.22 (s,lH).
Step C: Ethyl (l-methylethyl)carbamate . , To a solution of ethyl chloroformate (21.7 9, 0.2 mol~ in 200 ml ether cooled to 0C was added dropwise 35.7 ml of isopropylamine with stirring and cooling. After complete addition of t~e amine, the reaction mixture was stirred at room temperature for an additional 0.5 hour. The reaction mixture was filtered, and the ether solution was washed with ` water, and dried over magnesium sulfate. Evapora-tion of the ether and distillation of the residue in .~ a Kugelrohr apparatus resulted in 22. 6 9 of the title compound ~.p.: 50-66DC (bath temperature) at l.S mm Hg.
.
Step D: Ethyl (chlorosulfenyl)(l-methyl-ethyl)carbamate .; .
To a solution of ethyl (l-methylethyl)-- carbamate (13.1 g, 0.1 mol) in 100 ml methylene ~ chloride cooled to 0C was added sulfur dichloride - (11.3 9, 0.11 mol) in one portion. While maintaining -~i the temperature of the mixture at 0C, pyridine (8.7 30 9, 0.11 mol) was added dropwise over eleven minutes; -~
After complete addition of the pyridine the temperature was allowed to rise to room temperature ,j,!
snd stirring was continued for additional 1.5 hours.
The mixture was let ~tand overnight. Methylene : 35 chloride was evaporated under vacuum and 100 ml hexane was added. Filteration of the pyridine ;
~' ' -.
. . :
ZS}f ~130 hydrochloride and evaporation of hexane resulted in an orange oil which was distilled in a Kugelrohr appara~us to give 12.5 g of the title compound Bp:
64-80 (bath temper~ture) at 1.4 mm Hg.
Step E: 3,3a,4,5-Tetrahydro-3a-metho~ycarbonyl-N-[4-(trifluoromethyl)phenyl]-N-[N'-(l-methyl-ethyl)-N'-(etho~cycarbonyl)aminosulfenyli-2H-benz[g]indazole-2-carbo~amide , To a solution of the title compound of Step (2.0 9, 4.8 mmol) in 50 ml methylene chloride cooled to 0CC was added triethylamine (1.0 9, 0.01 mol~ and ethyl (chlorosulfenyl)(l-methylethyl)carbamate from Step D (1.4 9, 7.7 mmol). The misture was allowed to warm to room temperature and stirred for one hour.
; The crude mi~ture was purified by silica column . 20 chromatography using ether-hexane (1:2) as eluent.
- The title compound (2.38 9) was obtained in about 90%
- purity (mp: 130-134). Extraction of the product : with ether-hexane (2:1) gave 1.8 9 of highly pure '. material mp: 139-140C.
lH NMR (CDC13); ~ 0.92 (t,3H), 1.26 (d,3H), 1-35 (d,3H), 1.95 (m,lH), 2.7 (m,lH), 2.95 (m,2H), 3.67 (s,3H), 3.8 (m,3H), 4.5 (m,2H), 7.2 (m,3H), 7.45 ; (d,3H), 7.65 (d,2H~.
E~amPle 2 3,3a,4,5-Tetrahydro-3a-metho~ycarbonyl-N-:' 14-(trifluoromethYl)Phenyl]-N-~l-methyl-propo~ylcarbonylsulfenyl)-2H-benz[g]-_ indazole-2-carboxamide.
~; 35 Step A: (l-methylpropoxycarbonyl)sulfenyl chloride ., ' ~' .
... .. , .......... . ..... .. : . ,,, . -: .
:: . .. ~ ,: . : . . . ~ . . , :,. ,. . . . -Z~3~3C~
Chlorocarbonylsulfenyl chloride (13.1 ~, 0.1 m~l) was mixed with 2-butanol (6.7 9, 0.09 mol3 and wa~med to about 35 to 40C for one hour. Distil-lation resulted in the title compound (5.93 9) ~p.
70C/0.8 mm Hg. NMR spectrum was ~onsistent with the structure.
Step B: 3,3a,4,~-Tetrahydro-3a-metho~ycarbonyl-N-[4-(trifluoromethyl)phenyl]-N-~l-methyl-propo~ycarbonylsulfeny~)-2H-benz[g]indazole-2-carboxamide.
To a solution of the title sompound of Step B
-~ (Example 1) (0.4 9, 0.96 mmol) in 5 ml methylene chloride was added triethylamine (0.12 9) and cooled to 0C. To this solution was added (l-methylpropoxy-car~onyl)sulfenyl chloride (Step A) (0.2 9, 0.0012 mol). The mixture was stirred at room temperature for one hour. At this stage thin layer chromatography indicated only partial conversion, therefor, addition- al amounts of (l-methylpro-poxycarbonyl)~ulfenyl chloride (0.2 93 and triethylamine (0.12 9) was added and the mi~ture was let stand overnight. The reaction mi~ture was subjected to silica gel column chromatography using hexane-ether (7:1) as eluent. The title compound was `-obtained (0.22 9) in high purity; m.p.: 125-126C.
lH NMR (CDC13): ~ 0.9 ~m,3H), 1.3 ~m,3H), 1.6 (m,2H), 1.9 ~m,lH), 2.B (m,3H), 3.67 (s,3H), 3.8 (d,lH), 4.5 (d,lH), 5.0 (m,lH), 7.05 ~m,3H), 7.25 (m,lH), 7.5 (d,2H), 7.57 (d,2H).
'.'-. '.
.
: ':
. .
~, : . . . . . . . . . .
,;,. . . . . . , ... . . . ~ ` ~ . . . . . :
.,. . - .
Z~130 . ~ ~ ..
3,3a,4,5-Tetrahydro-3a-methoxycarbonyl-N-[4-(trifluoromethyl)phenyl~-N- (dibutyl amino-sulfenyl)-2H-benzrglind~zole-2-carbo~ami~e Step A: N,N'-bis-(dibutylamino)disulfide To a solution of dibutylamine (5Z g, 0.4 mol) in 200 ml hexane cooled to 0C was added ~ulfur mono-chloride (13.5 9, 0.1 mol) dropwise with stirring over a period of 20 minutes. The rea~tion mixture was warmed up to room temperature and stirring was continued for 30 minutes. The reaction miature was filtered and he~ane was evaporated to yield 30.1 9 of the title compound.
Step B: Dibutylaminosulfenylchloride To a solution of N,N~-bis-(dibutylamino)disul-`~ fide (13.2 g, 0.05 mol) in 12 ml carbontetrachloride was added. Sulfuryl chloride ~6.75 9, 0.05 mol) was added dropwise at ambient temperature. Then heated to about 60C for 10 minutes, and distilled to give ; the title compound (7.55 9) as a yellow liquid. Bp:
`~ 80-87C at 0.6 mm Hg.
'.'' Step C: 3,3a,4,5-Tetrahydro-3a-metho~ycarbonyl-N-14-, 30 (trifluoromethyl)phenyl~-N-(dibutylamino-sulfenyl)-2H-benz[g]indazole-2-earbosamide.
. :
To a solution of the title compound of Step (Example 1) (0.4 9, 0.96 mmol) in B ml methylene chloride cooled to 0C was added triethyla~ine (0.15 9) and dibutylaminosulfenylchloride (0.2 9~.
.. ..
.. .
., - .. . . ...
.. . ,, : . . . ... . .
2;1~J(~130 The reaction mixture was warmea to room temperature and stirred for one hour. l`he mi~ture was subjected to silica gel column chromatography using hexane-ether (6:1) as the eluent. The title compound was obtained (0.24 g) in high purity.
H NMR (CDC13): ~ 0.7 to 1.7 ~m,14H), 1.9 (m,lH), 2.6 to 3.1 (m,7H), 3.67 (s,3H), 3.75 (d,lH), 4.45 (d,lH), 7.1 (m,3H), 7.25 (m,lH), 7.4 (d,2H), 7.6 (d,2H).
Esample 9 7-Chloro-3,3a,4,5-tetrahydro-3a-methoxy-carbonyl-N-[4-(trifluoromethyl)phenyl]-N-: -[N'-(methyl)-N'-(hexoxycarbonyl)amino-; sulfenyll-2H-benzralindazole-2-carbo~amide ;.~ "
Step A: ((2-(3-chlorophenyl)ethyl)methanesulfonate To a 0C solution of 30.0 g of 3-chloro-; phenethyl alcohol and 15.3 ml of methane sulfonyl chloride in 150 ml of THF was added, dropwise, a solution of 2B.0 ml of triethylamine in 50 ml of THF. The reaction was warmed to room temperature, stirred overnight, and then filtered. The filtrate was partitioned between aqueous sodium bicarbonate and ether. The organic extracts were then dried over ` magnesium sulfate, filtered and concentrated under 3Q reduced pressure to afford 45.93 9 of a clear, colorless oil.
:: .
Step B: 3-chlorobenzenebutanoic acid ~
. .
To a mixture of 8.0 g of 60~ ~odium hydride in 300 ml of THF, under N2, was added dropwise a ; solution of 31.0 ml of diethyl malonate in 50 ml of ., ' ;~ ' ;
", .~
.
Z~3~?13~
THF. Upon complete addition of the diethyl malonate, a pale yellow homogenous solution was obtained. To this was added a solution of 45.93 9 of the sulfonate from Step A and the mixture was then heated at reflu~
` overnight. The reaction was then cooled to room temperature, poured into 400 ml of lN HCl, and e~tracted with ether. The ether extracts were dried over magnesium sulfate, filtered and concentrated under reduced pressure to afford 68.9 g of a yellow oil. The crude oil was dissolved in 400 ml of methanol, 100 ml of H2O and 40 ml of 50~ aqueous NaOH. The reaction was stirred overnight and the methanol was then removed at reduced pressure. The crude residue was partitioned between H2O and ether, the aqueous extracts were acidified with concentrated HCl and then e~tracted several times with ether. The ether e~tracts were dried over maqne- sium sulfate, filtered and concentrated to afford 51.7 9 of a yellow oil. The crude residue was dissolved in 200 ; ml of toluene and heated at reflux for 4 days under N2 to effect decarbo~ylation. After this time toluene was removed by concentration at reduced pressure to afford 35.72 9 of a yellow oil. lH NMR
; analysis of the crude product was consistent with 3-chlorobenzene- butenoic acid of purity estimated to be 80%. The crude product was used without further purification directly in the ne~t step.
-` 30 Step C: 6-chloro-3,4-dihydrG-1(2H)-naphthalenone ` A mi2ture of 35.72 of the produc~ from Step B
~nd 50 ml of thionyl chloride was heated-at reflus for 2 hours and then stirred at room temperature for 18 hours. After this time thionyl chloride was .
- . , . ~ . . , : ~.: : . - .
, ..
removed at reduced pressure and the product was dissolved in carbon tetrachloride and concentrated at reduced pressure The residue was dissolved in 150 ml of dichloroethane cooled to 0C and 28 g of aluminum chloride was added portionwise over about 1 hr in approximately 3 9 portions. After ~tirring for 3 hrs the reaction was poured over a mixture of ice/lN HCl and extracted three times with methylene chloride. The organic extracts were dried over ` magnesium sulfate and concentrated to appro~imately 30 9 of a brown oil. Chromatography on silica gel with 1~ ethyl acetate/hexane afforded 17.B3 g of 6-chloro-3,4-dihydro-1(2H)-naphthalenone as a brown oil. lH NMR was consistent with the structure.
~ Step D: 7-chloro-3,3a,4-5-tetrahydro-N-[4-(tri-'!`: fluoromethyl)phenyl]-2H-benz[g~-indazole-Z0 2-carboxamide : .
A mi~ture of 6-chloro-3,4-dihydro-1(2H)-naphthalenone (Step C), 2.5 9 of dimethylamine hydrochloride, 1.0 g of paraformaldehyde, 0.7 ml of concentrated HCl and 15 ml of ethanol was combined and heated at reflux for 18 hrs. ~he reaction was then concentrated at re- duced pressure and partitioned between H2O and ether. The aque~us extracts were made baic with lN NaOH and then extracted three times with ether. The ether e~tracts ` were dried over magnesium sulfate and concentrated to 4.64 9 of a ~ellow oil. This compound was dissolved in 25 ml of ethanol and 1.5 ml of hydrazine hydrate was added followed by S to 6 drops of 50~ 80dium hydro~ide. The reaction was ~hen heated at reflux, under N2, for 2 to 3 hrs after which time it was cooled and most of the ethanol was removed by ., . .
. . . - : - -. .
Zl" t~-130 concentration at reduced pressure. The crude residue was partitioned between 6aturated aqueous ~odium bicarbonate end methylene chloride. The methylene chloride e~tracts were dried over magnesium sulfate and filtered. The methylene chloride e~tracts were then combined with 3.5 g of 4-trifluoromethylphenyl isocyanate and stirred under N2 overnight. The reaction was then concentrated and the crude residue triturated with ether to afford 3.35 9 of the title compound as a white powder, m.p. 196 to 199C.
lH NMR (CDC13 9 ~ 1. 9 (m, lH), 2 . 2 (m, lH), 3 . O (m, 2H), 3.5 (m,2H), 4.43 (m,lH), 7.24 (m,2H), 7.55 (d,2H), 7.67 (d,2H), 7.92 (d,lH~, 8.20 (s,lH).
. .
Step E: 7-chloro-3,3a,4,5-tetrahydro-3a-methoxy-carbonyl-N-[4-(trifluoromethyl)phenyl]-2H-benz[g]indazole-2-carboxamide A solution of 50 ml of THF and 6.7 ml of - diisopropylamine was cooled under N2 to -78C and then 17.5 ml of 2.5 M n-butyllithium in hexane was ; added. After 5 min, a solution of 7.B g of the title .~ 25 compound of Step D in 15 ml of THF was added dropwise and the dark red solution that formed was stirred at -78C for an additiGnal 15 min. After this time a solution of 4.6 ml of methyl chloroformate in 10 ml of THF was added dropwise and the red color dissipated rapidly. The reaction was warmed to room temperature and after 1 hr guenched with 5% aqueouis sodium bicarbonate. The reaction mi~ture was partitioned between ether and 5% aqueous ~odium bicarbonate. The ether e~tracts were dr~ed o~er magnesium sulfate and concentrated to 14.1 9 of a yellou oily solid. The crude product uas triturated :~
':
. . ., , .: : . . - : ~ .
2i}~ 3~
with ether and the resulting white precipitate was filtered and dried to afford 5.56 9 of the title compound as a whi~e solid, m.p. 234 to 236C.
. 1H NMR(CDC13) 6 2.1 (m,lH), 2.7~ (m,lH), 2.95 (m,2H), 3.71 (s,3H), 3.75 (d,lH, Jo6Hz), 4.59 (d,lH, J~6Hz), 7.25 (m,2H), 7.57 (d,2H), 7.66 (d,2H), 7.94 (d,lH), 8.1B (d,lH).
Step F: 7-chloro-3,3a,4,5-tetrahydro-3a-methoxy-,~ carbonyl-N-14-(trifluoromethyl)phenyl]-N-[N'-(methyl)-~'-(hexoxycarbonyl)amino-sulfenyl]-2H-benz[g]indazole-2-carboxamide To a suspension of the title compound of Step E above (2.2 g, 0.005 mol) in 25 ml methylene chloride cooled to 0C was added triethylamine (1.0 g) and hexyl (chlorosulfenyl)(methyl)carbamate, (prepared in a manner similar to Example 1, Step D), ~ (2.5 9 75% pure) dropwise at 0C. The mixture was - stirred at room temperature for additional one hour.
:~ The reaction mixture was concentrated under high vacuum and subjected to silica gel column chromatography using hexane-ether (1:1) as an eluent. The title compound (2.5 9) was obtained, melting point 128-129C in high purity.
H NMR (CDC13) ~ O.B7 (t,3H), 1.18 (m,8H), 1.9(m,1H), ` 2.B (m,3H), 3.5 (s,3H), 3.66 (s,3H), 3.7 (m,3H), 4.5 - 30 (d,lH), 7.05 (m,3H), 7.35 (d,2H), 7.6 td,2H).
~sing the procedures described in Examples 1 to 4 with o~vious modifications, the compsund~ -exemplified in E~amples 5 to 28 were prepared.
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' R~O~CH3 '. C =~
. C~3 ~N-S-Z
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Example R2 Z m.p.-C lH NMR (~ i~ ppm) : 20 ln CDC13 . .
H NtCH3)CtO)OC4H9 134 1.0(t,3H), 1.2(m,4H), - l.9(m,1H), 2.6-3(m,3B), ~ 3.5(~,3H), 3.66(6,3H), ; 25 3.7(m,2H), 3.75(d,1H), 4.45(d,1H),7.1(m,3H), ` 7.25(m,lH), 7.35(d,2H), ;1 7,6(d,2H).
6 H N(CN3)C(O)OC2H5 121-123 0.88(t,3H), l.9(m,1H), 3C 2.6-3(m,3H), 3.5(s.3H), 3.66 ~,3H), 3.8(m,3H), 4.47(d,1H), 7.11(m,3H), , 7.25 tm,lN), 7.35(d,2H), 7.6~d,2H).
.1 ~ . .
.
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.
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; Example R2 Z m.p.-C lH NMR (6 ~n ppm) -:
~ ~ CDC 13 7 6-F N(CH3)C(O)OC4H9 120 0.83tt,3H), 1.2(m,4H), l.B5(m,1H), 2.7(m,2H),';
3.0(m,1N), 3.5(c,3H), 3.66(e,3H), 3.75(m,3H), ; 4.5(d,1H), 7.0(m,3H), 7.35(~,2H), 7.6(d,3H).
~; 8 H N(CH3~C(O)~cy~loC6H11 175-176 0.6-1.7(m,10H), l.9(m,1H), 2.6-3.0(m,3H), 3.51(s,3H), ~ 15 3.65(s,3H), 3.75(d,1H), : 4.35(m,1~), 4.45 (d,lH), 7.1(m,3H), 7.25(m,1H), ~^ 7.35(d,2H), 7.6(d,2H).
; 9 H N(cH3)c(c)oc8Hl71~4-145 0.88(t,3H), 1.21(m,12H), `~ 20 l.9(m,1H), 2.7(m~1H), 2.9~m,2H), 3.5(m,3H), 3.65(m,3H), 3.75(m,3H), 4.5(d,1H), 7.1(m,3H), ~ 7.25(m,1H), 7.35(d,2H), , '~ 25 7.6 ( d,2H ) .
( 10 ~ N(CH3)C(O)OcloH2l 76-780.88(t,3H), 1.25(m,16H).
-~ l.9~m,1H), 2.7(m,1H), -2.9(m,2H), 3~5(s,3H), , - 3.66(s,3H), 3.75~m 3H), ,~ . , ~ 30 4.5(d,1H), 7.15(m,3H), s~ 7.25(m,1H), 7.35(d,2H), 7.6 (d,2H).
.
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Example R2 z m.p.-C lB ~MR (6 in ppm) ~ p CDC13 11 6-F N-lCH(CN3~2~C(O)OC2H5 143.5 O.91(t,3H), 1.27(d,3H), 1.35~d,3H), l.9(m,lH), 2.75(m,2H), 3.05~m,1H), 0 3.67(s,3H), 3.75~m,3H), 4.5(m,2H), 7.25(m,3H), 7.45(d,2H), 7.6(d,2B).
12 H N(cH3)c(o)ocl2H25 0.88(t,3H), 1.26(m,20H), l.9(m,1H~, 2.7(m,1H), 2.9(m,2H), 3.5(~,3H), 3.66(~,3H1, 3.75(m,3H), 4.5(d,lH), 7.1(m,3H), ~- 7.25(m,lH), 7.35(d,2H), 7.6(d,2H).
13 H N(CH3)c(O)~c6Hl3 0?88(t,3H), 1.26(m,8Hj, l.9(m,1H), 2.7(m,1H), 2.9(m,2H), 3.51(~,3H), 3.66(6,3H), 3.75(m,3H), 4.5(d,2H), 7.1(m,3H), 7.25(m,1H), 7.35(d,2H), . 7.6(d,2H).
14 7-Cl C(0)0-6ec-C4Hg 132 0.88(t,3H), 1.3(m,3H), ; 1.6(m,2H), l.9(m,1H), ~ 2.6-3.0(m.3N). 3.88(s,3H), f,` 30 3.8(d.1H), 4.5(d,1H), S.O(m,lH), 7.0~m,3H), 7.35(d,2H~, 7.6~d,2H).
15 7-Cl N~ICH(CH3)2]C()C2Hs 152 Oo9~t~3N)~ 1.26(d,3H3, 1.35~,3H), 1.9(m,1H), 2.7(m,1H), 2.9(m,2H), 3.67( ,3H), 3.8(m,3H), 4.5(m,2H~, 7.14(m,2H), 7.4(m,3H), 7.6(d,2A).
.~ , :
,, ' :
r ~
2~0(~130 ' E~ample R2 Z m.p.-C lN NMR (~ in ppm) S ln CDC13 : :.
16 7-Cl N(CH3)C(O)OC2Hs ~ 0.88(t,3H), 1.9~m,1H), 2.65(m,1H), 2.9(m,2H), 3.49(c,3H), 3.66(~,3H), 3.B(m,3H), 4.5(d,1H), 7.07(m, 3H), 7.35(d,2H), 7.6(d,2H).
17 7-Cl N(cH3)c(o)oc8Hl7 103-106 0.88(t,3H), 1.23(m,12H), l.9(m,lH), 2.65(m,lH), 2.85(m,2H), 3.5(c,3H), 3.66(s,3H), 3.75(m,3H), .45(d,lH), 7.05(m,3H), , 7.35(d,2H), 7.6(~,2H).
`~ la 6-F C(O)O-sec-C4H9 125-126 O.9(m,3H), 1.3(m,5H), - 20 l.9(m,1H), 2.75(m,2H), 3.0(m,1H), 3.7(6,3H), . ., 3.8(d,1H), 4.5(d,1H), ~ ..
5.0(m,1H), 6.8(m,1H), 7.05(m,2H), 7.45(d,2H), 7.6(d,ZH).
19 7-Cl ~(CH3)C(O)OC4H9 125-127 0.82(m,3H), 1.2(m,4H), l.9~m,1H), 2.65(m,1H), 2.85(m,2H), 3.5(6,3H), 3.66(~,3H), 3.75(m,3H), 4.45(d,lH), 7.05(m,3H), 7.35(d,2H), 7.6(d,2H).
7-Cl NlcH(cH3)2lc(o)oc4H9 - 0.84(t,3H), 1.25(m,10H), l.9(m.lN), 2.65~m,lH), 3.~6~c~3K), 3.7~m.3H).
4.45(m,2B), 7.15(m,2H), 7.4(m,3H), 7.6(d,2H).
i, .
Z~'(!13~0 Example R2 Z m.p.-C lH NMR (~ in ppm) ~ CDC13 21 7-Cl N( Q 3)C(O)ocl2H2~5 0.88(t,3H), 1.2(m,20H), l.9(m,1H), 2.65(m,1H), - 2.9~m,2H), 3.5(s,3H), 3.67(6,3B), 3.75(m,3H), 4.5(d,1H), 7.05(m,3H), 7.35(d,2H), 7.6(d,2H).
22 7-Cl N(CH3)C(O)O-cycloC6H11 87-91 0.8-1.7(Bro~d m,lOH), ; 2.65(m,1H), 2.9(m,2H), 3.51(s,3H), 3.66(s,3H), 3.75(d,lH), 4.35(m,lH), 4.q5(d,1H), 7.05(m,3H), 7.35(d,2H), 7.6(d,2H).
23 7-Cl N(CH3)C~0)0(CH2)20C4H9 ~ 0.9 ~t,3H), 1.4 (m,4H) - 20 1.9 (m,lH), 2.7 (m,lH) 2.9 (m,2H), 3.3 (m,4H) 3.5 (6,3H), 3.67 (~,3H), 3.9 (m,3H), 4.5 (d,lH), ~i 7.1 (m,3H), 7.4 (d,2H), 7.6 (d,2H).
``~ 24 7-Cl N(CH3)~(O)OC14H29 - 0.87 (t,3H), 1.26 (m,24H), ` 1.9 (m,lH), 2.65 (m,lH), - 2.9 (m,2H), 3.5 (~,3H), 3.68 ~,3H), 3.75 (m,3B), ~.47 (~,1H), 7.05 tm,3H), -~ 7.35 (d,2H), 7.57 (d,2H).
- 25 7-Cl N~CH3)C(O)OC16H33 ~ 0.87 (t,3H), 1026 (m,28H), ~ -1.9 (m,lH), 2.65 (m,lB), 2.9 (m,2H), 3.5 ~,3H), 3.67 (~,3H), 3.75 (m,3H), 4.47 (d,lB~, 7.05 (m,3H), 'I`
7.35 (a,2H), 7.6 (d,2H).
, : . .
.~,, Zl~Q130 ::
Ex~mple R2 Z m.p.-C lH NMR (6 in ppm) ~ D CDCl3 .
26 7-Cl N(cH3)c(o)ocl8H37 0.9 tt,3H), 1.26 (m,32H), ` 1.9 (m,lH), 2.65 (m,lH), 2.9 (m,2H), 3.5 (s,3H), 3.67 ~m,3H), 3.75 (m,3H), 4.5 (d,lH), 7.05 (m,3H), 7.35 ld,2H), 7.6 (d,2H~.
27 7-Cl N(cH3)c(o)oc22H45 O.BB (t,3H), 1.26 (m,40~, l.9 (m,lH), 2.65 (m,lH), 2.9 (m,2H), 3.5 (s,3H), 3.6~ (m,3H), 3.75 (m,3H), 4.4B (d,lH), 7.06 (m,3H), ' 7.3~ (d,2H), 7.6 (d,2H).
~`~ 28 7-Cl N~cH3)c(o)o(cH2)2o(cH2)2oc4Hg 0.91 (t,3H), 1.4 (m,4H), l.9 (m,lH), 2.i (m,lH), ~ 2.9 (m,2H), 3.5 (s,3H), -~ ` 3.67 (s,3H), 3.7 (m,9H). 7.
~ 4.0 (m,lH), 4.2 (m,lH).
.-1 4.5 (d,lN), 7.6 (m,3H), 7.4 (d,2H), 7.6 (d,2H).
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E~ample 29 1-(4-chlorophenyl)-5-(9-fluorophenyl)-4,5-dihydro-N-t4-(trifluoromethyl)phenyl]-N-[N~ methylethyl)-N~-(etho~ycarbonyl)aminothiol~-lH-pyrazole-3-carb~amide Step A: Ethyl (chlorosulfenyl)(l-methylethyl)-carbamate To a solution of ethyl (l-methylethyl)carbamate (13.1 9, 0.1 mol) in lO0 ml of methylene chloride cooled to 0C was added sulfur dichloride (11.3 9, 0.11 mol) in one portion. While maintaining the temperature of the mixture at 0C, pyridine (8-? 9, 0.11 mol) was added dropwise over eleven minutes.
After complete addition of the pyridine the temperature was allowed to rise to room temperature and stirring was continued ~or additional 1.5 hours.
The mi~ture was let stand overnight. Methylene chloride was evaporated under vacuum and 100 ml hexane was added. Filteration of pyridine hydrochloride and evaporation of he~ane resulted in an orange oil which was distilled in a Kugelrohr apparatus to give 12.5 9 of the title Compound ~.P.:
69-B0 (bath temp.) .; 1,,~,.
Step B: 1-(4-chlorophenyl)-5-(4-fluorophenyl)-4,5-dihydro-N-14-(trifluoromethyl)phenyl~- -N-tN'-(l-methylethyl)-N'-(ethoxycarbonyl)-ol] IH-pyrazole-3-Farbosamide To a solution of 1-(4-chlorophenyl)-5-(~-fluoro-phenyl)-4,5-dihydro-N-14-(tri~luoromethyl)phenyl]-lH-pyrazole-3-carbo~amide (0.95 g, 0.002 mol) in 10 ml .. , " ,' .
:
-,~ . ' Z~lt!130 of methylene chloride cooled to 0C was added triethylamine (0.25 9) followed by the title compound of Step A (0.5 9, 0.0025 m~l). The reaction mi~ture was all~wed to warm to room temperature with ~tirring for one hour. Methylene chloride (50 ml) was added and the mi~ture was washed with water, dried over magnesium sulfate and filtered. The ~olvent was evaporated and the residue was purified by silica gel column chromatograph using he~ane:ether (2:1) 95 the ; eluent. Obtained 1.0 9 of the title compound, m.p.: 136-137DC, 'H-NMR (CDC13): ~ 7.7 (d,2H), ~.4 (~, 2H), 7.0 (m, 6H), 6.3 (d, 2H), 5.2 (d of d, lH~, 4.5 (m, lH), 3.75 (m, 3H), 3.05 (d of ~, lH) 1.3 (d of d, 6H), ~.87 (t, 3H).
E~ample 30 3,4-bis-(9-chlorophenyl)-N-[4-(trifluoromethyl)-phenyl]-N-[N'-(l-methylethyl)-N'-(etho~ycarbonyl)-aminothioll-9~5-dih~dro-lH-pyraz~le-l-carbo~mide , T~ a solution of 3,4-bis-(4-chlorophenyl)-N-[9-(trifluoromethyl)phenyl)]-4,5-dihydro-lH-pyrazole-2S l-carbo~amide (Q.466 9, ~.001 mol) in 5 ml of methylene chloride cooled to 0C was added 0.3 9 of triethylamine and ethyl (chlorosulfenyl)(l-methyl-`i ethyl)carbamate (0.5 9). The mi~ture was allowed to warm to room temperature and let stand overnigh~. 20 ml CH2C12 was added and the mi~ture was washed with water ad dried over MgSO4 and filtered. The solvent ;
was evaporated under vacuum. The residue was purified by silica gel column chromatogr~phy using CH2C12:Butylchloride mi~ture (1:1) ~s a primary eluent followed by ether. The title compound was obtained in high purity (0.28 9), m.p.: 65-68C.
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. :,,: ' ' ., ~ 30 : 36 lH-NMR (CDC13), ~ 7.65 (d, 2H), 7.5 (d, 2H~, 7.27 (d, 2H), 7.17 (S, QH), 7.0 (d, 2H), 4.6-4.3 (m, 3H), 3.95 5(d-of d, lH), 3.8 (q, 2~), 1.3 (m,-6H), 0.95 (t, 3H).
The following additional E~amples (Tables B
and C) employed procedures similar to those described in the previous E~amples 29 and 30 ~r in the -~ 10 disclosed literature.
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rJ~cr3 - Example X m.p.C 'H-NMR ~ ln ppm) in CDC13 : .
31N[cH(cH3)2lc(o)oc4H9 165-170 7.23 ~d, 2H), 7.4 ~a, 2H), 7.0 lM, 6H), 6.3 (d, 2H), 5.2 (d of d, lH), 4.5 ~M, lH), 3.75 (M, 3H), 3.1 (d of d, lH), 1.4 2~ ~M, lOH), .85 (t, 3H) 32NlcN(cH3)(c2H5)]c(o)oc2H5 ~ 7.23 (d, 2N), 7.4 ~d, 2H), ., 7.0 ~M, 6H), 6.3 (d, 2H), 5.2 (d of ~, lH), 4.5 lM, lH), 3.75 (M, 3H), 3.1 (d of d, lH), 1.8 (M, SH), 0.9 (M, 6H).
. .
~ 35 .. ..
.
,, 2~ 30 Example X m.p.C 'H-NMR ~ ~n ppm) ln CDCl~
. _ 33 C(O)OCHtCH3)(C2H5) 159-161 7.25 (d, 2H), 7.55 (d, 2H), 7.0 (M. 6H), 6.25 (d, 2H), 5.2 (d of d, lH), 5.0 (M, lH), 3.75 (d of d, lH), 3.1 (d of d, lH), 1.65 (M, 2H), 1.28 (d, 3H), 0.9 (t, 3H).
34 N(CH3)C(O)O(cyclo C6Hll) 147-150 7.2 (d, 2H), 7.4 (d, 2H), 7.0 (M, 6H), 6.3 ta, 2H), 5.2 (d of d, lH), 4.3 -~ (M, lH), 3.7 (d of d, lH), 3.5 (5, 3H~, 3.2 (d of d, lH), 1.3-0.9 (M, lOH).
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i ~LE Q R3 Rl m.p.C 'H-NMR (6 in ppm) . . :
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.,; 35 5-N~CH3)C~0)0-cec-C4H9 Cl CF3 83-84 7.8-6.9 (m, 12H), . ,.3 ~ . 6-4 . 3 (M, 3H ), 4 . 0 ':
' (M, lH), 3.52 (S, 3H), 1.25 (M, 2H), 1.0--0.7 (M, 6H ) .
~.:
36 S-C(0)0-cec-C4Hg Cl CF3 78-60 7.7-7.0 (M, 12H), 5.0 ., (M, lH), ~1.45 (M, 2H), ~,, .
` ~.0 ~M, lB), 1.6 (M, .~ 2N), 1.3 ~d, 3H), 0.9 .. . .
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?130 EX- Q R3 Rl m.p.-C 'H-NMR (6 in ppm) AMPLE _ _ 37 S-C(O)O-6ec-CqNg Cl Cl 66-69 7.4-6.9 (M, 12H), 5.0 (M, lH), 4.5 (M, 2H), 4.0 (M, lH), 1.6 (M, 2H), 1.28 (d, 3H), 0.9 (M, 3H).
: .
; 38 CO2CH3 Cl CF3 151-154 7.7-7.0 (m, 12H), 4.7 ~d,d,lH), 4.5 (d,d,lH), 4.1 (d,d,lH), 3.86 ; (s,3B).
39 COCH3 F CF3 157-159 7.7-7.0 (m,12H), 4.7 (d,d,lH), 4.5 (d,d,lN), 4.1 (d,d,lH), 3.86 (~,3H).
S-N(cH(cH3)2)so2c2H5 Cl CF3 oil 7.65 (m,2H), 7.25 (m,4H), 7.05 (m,lH), 4.6-3.9 (m,3H), 3/65 (m,lH), 3.03 ` (q,2H), 1.36 (t,3H), 1.24 , (d,6H1-41 COCH3 Cl CF3 166-168 7.6-7.0 (m,12H), 4.7-4.0 (m,3H), -2.3 (~,3H).
. ' ~2 COCH3 F Cl 187-190 ~.5-7.0 ~m,12H), .6 (m,lN), 4.4 (m,lH~, 4.0 (m,lH), 2.26 (s,3H).
"
,. .
.. .
.;~ .
. . .
2~ 30 5 EX- Q R3 Rl m.p.-C 'B-NMR (~ ln ppm UMPLE __ _ Ç3 COCH3 , F Br181-186 7.6-7.0 (m,12H), 4.65 (m,lH), 4.4 (m,lN), ^ 10 q.0 (m,lH~, 2.25 ~,3H).
44 CO2Me F CF380-86 COPh F CF3176-179 46 COEt Cl CF3 169-170 , 47 EtCOCO Cl CF3 166-167 48 CO-~-Bu Cl CF3 60-62 ~ 49 COCH3 Cl Cl io5-206 .' . .
~ 25 50 COEt Cl Cl157-158 , .
51 CO2Me Cl Cl162-166 52 4-ClPhCO Cl CF3209-211 , ~0 53 t-BuCO Cl CF3140-145 :,.
54 PhOCO Cl CF3150-155 , ,~ 35 .' ' ~', ~', .
. ~ .
.: :
- - : ,.
`
2~ 130 Example 5S
- N~acetyl-3,4-bist4-chlorophenyl)-4,5-dihydro-N-[4-(trifluoromethyl)phenyl]-lH-pyrazole-l-__~lk~smi~e ' .
The compound of Step D of Esample 6 (0.65 9) was dissolved in tetrahydrofur~n ~20 ml) and treated with 60% sodium hydride in oil (0.12 9). After the - evolution of hydrogen was complete (30 minutes), acetic an~ydride (D.6 ml) was ~dded and the misture was stirred at room temperature for 16 hours. The reaction was diluted with saturated agueous ammonium chloride solution (15 ml) and ethyl acetate (30 ml).
~` The organic layer was dried with magnesium sulfate and evaporated. The residue was subjected to chromatography on silica gel with he~anes/ethyl acetate (3:1) as eluent. Addition of methanol (10 ml) to the product gave, after filtration, the title compound (0.4 9). m.p. 166 to 168~C.
NMR (CDC13) 7.6-7.0 (m, ArH, 12H), 4.7-4.0 (m, 3H, CH and CH2), 2.3 (s, COCH3, 3H).
:' , . .
,.......................................................................... .
~ 35 ;'~
'' ' '' '' :' ., .
. " . : .
211t~0130 Table 1 : 5 .
N~
~N J~R
S--N
R~, : 15 . . Rl R2 B R8 Rg 4-CF3 5-Cl H Me OEt ~ 4-CF3 5-Cl Me Me OEt 9-CF3 H CO2Me Me OEt . 4-Cl H CO2Me Me OEt :
4-Br H CO2Me Me OEt 4-OCP3 H CO2Me Me OEt . 4-CF3 5-Cl CO2Me Me OEt 4-C1 5-Cl CO2Me Me OEt ~ .
4-OCF3 5-Cl CO2Me Me OEt 4-CF3 5-CP3 C~2Me Me OEt 4-CF3 5-F CO2Me Me OEt .
4-CE3 5-Cl Ph Me OEt . 30 4-CF3 5-C1 9-Cl-Ph Me OEt :; 4-CF3 5-Cl CO2Et Me OEt . 4-CF3 5-Cl H Me O-n-Bu :' 4-CF3 4-F ~ Me O-n-Bu 4-CF3 H Me Me O-n-Bu . 35 4-CF3 5-Cl Me Me O-n-Bu 4-CF3 5-Br Me Me O-n-Bu 2~0~130 Rl R2 B R~ Rg .
4-CF3 4-F Me Me O-n-Bu 4-CF3 H COzMe Me O-n-Bu 4-Cl H C02Me .Me O-n-Bu 4-~r H CO2Me Me O-n-Bu 4-OCF3 H CO2Me Me O-n-Bu 4-CF3 5-Cl CO2Me Me O-n-Bu -~
4-C1 5-CI CO2Me Me O-n-Bu 4-Br 5-Cl CO2Me Me O-n-Bu 4-OCF3 5-Cl CO2Me Me O-n-Bu 9-CF3 5-Br CO2Me Me O-n-Bu 9-C1 5-Br CO2Me Me O-n-~u .
4-Br 5-Br CO2Me Me O-n-Bu 4-OCF3 5-Br CO2Me Me O-n-Bu 9-CF3 4-F CO2Me Me O-n-Bu 4-C1 4-F CO2Me Me O-n-Bu :
4-Br 4-F CO2Me Me O-n-8u 4-OCF3 4-F CO2Me Me O-n-Bu 4-CF3 5-CF3 CO2Me Me O-n-Bu .`
4-CF3 5-P CO2Me Me O-n-Bu .~! 25 4-CF3 5-Cl Ph Me O-n-Bu .. ~ 4-CF3 5-C1 4-Cl-Ph Me O-n-Bu 4-CF3 S-Cl ~O2Et Me O-n-Bu ~. 4-CF3 5-Cl Me Me O-n-hexyl ~ 4-CF3 H CO2Me Me O-n-he~yl 4 Cl H CO2Me ~e O-n-hesyl , 4-Br H CO2Me Me O-n-hexyl 4-OCF3 H CO2Me Me O-n-he~yl .~, 4-CF3 S-Cl C02Me Me O-n-he~cyl 4-C1 5-C1 C02Me Me O-n-he~yl .. ..
`~ 4-Br 5-Cl CO2Me Me O-n-he~yl ..
4-OCF3 5-Cl CO2Me Me O-n-hesyl 4-CF3 5-~r C02Me Me O-n-he~yl .... .
': ;
. '',' :-Z~ 130 . ~
Rl R2 B R8 Rg 4-C1 5-Br CO2Me Me O-n-he~yl 4-~r 5-Br CO2Me Me O-n-he~yl 4-OCF3 5-Br CO2Me Me O-n-he~yl 4-CF3 4-F CO2Ne Me O-n-hesyl 4-C1 4-F CO2Me Me O-n-hexyl 4-Br 4-F CO2Me Me O-n-hesyl 4-OCF3 4-F CO2Me Me O-n-he~yl 4-CF3 5-CF3 CO2Me Me O-n-he~yl 4-CF3 5-F CO2Me Me O-n-hesyl 4-CF3 5-Cl Ph Me O-n-hexyl 4-CF3 5-C1 4-Cl-Ph Me O-n-he~yl 4-CF3 5-Cl CO2Et Me O-n-he~yl 4-CF3 S-Cl Me Me O-n-octyl . 4-CF3 H CO2Me Me O-n-octyl , 20 4-Cl H CO2Me Me O-n-octyl ; 4-Br H CO2Me Me O-n-octyl 4-OCF3 H CO2Me Me O-n-octyl ~ 4-CF3 5-Cl CO2Me Me O-n-octyl ; 4-C1 5-Cl CO2Me Me O-n-octyl 4-Br 5-Cl CO2Me Me O-n-octyl ~ 4-OCF3 5-Cl CO2Me Me O-n-octyl .~. 4-CF3 5-Br CO2Me Me O-n-octyl 4-C1 5-Br CO2Me Me O-n-octyl 9-Br 5-Br CO2Me Me O-n-octyl 4-OCF3 5-Br CO2Me Me O-n-octyl 4-CF3 4-F CO2Me Me O-n-octyl 4-C1 4-F CO2Me Me O-n-octyl 4-Br 4-F CO2Me Me O-n-octyl 4-OCF3 4-F CO2Me Me O-n-octyl 4-CF3 5-CF3 CO2Me Me O-n-octyl 4-CF3 5-F C2Me Me O-n-octyl ,~
., , .:
~6 Rl ~2 B RB ~9 :.
4-CF35-Cl Ph Me O-n-octyl 4~CF35-C14-Cl-Ph Me O-n-octyl 4-CF35-Cl c02Et Me O-n-octyl g-CF35-Cl Me Me O-n-decyl 4-CF3 H CO2Me Me O-n-decyl 4-Cl H CO2Me Me O-n-decyl 4-Br H CO2Me Me O-n-decyl 4-OCF3 H CO2Me Me O-n-decyl 4-CF35-Cl CO2Me Me O-n-decyl 4-C15-Cl CO2Me Me O-n-decyl ..
~-Br 5-Cl CO2Me Me O-n-decyl 4-OCF35-Cl CO2Me Me O-n-decyl .
. 4-CF35-Br CO2Me Me O-n-decyl 4-C15-Br CO2Me Me O-n-decyl ; 20 4-Br 5-Br CO2Me Me O-n-decyl 4-OCF35-Br C2Me Me O-n-decyl `- 4-CF34-F CO2Me Me O-n-decyl 4-C14-F CO2Me Me O-n-decyl 4-Br 4-F CO2Me Me O-n-decyl 4-OCF34-F CO2Me Me O-n-decyl :
~,. 4-CF35-CF3 CO2Me Me O-n-decyl .. 4-CF35-~ CO2Me Me O-n-decyl 4-CF35-Cl Ph Me O-n-decyl -.................. 4-CF35-C14-Cl-Ph Me O-n-decyl ::
4-CF35-Cl Co2Et Me O-n-decyl :: 4-CF35-Cl Me Me O-n-dodecyl . 4-CF3 H CO2~e Me O-n-dodecyl .
: 4-Cl H CO2Me Me O-n-dodecyl :
.. 4-Br H CO2Me Me O-n-dodecyl ~::
4-OCF3 H CO2Me Me O-n-dodecyl :
4-CF35-Cl CO2Me Me O-n-dodecyl ., .
., .: : . : . .. . . . ~
2'~ ?130 Rl R2 - -_8 9_ 4-C1 5-Cl CO2Me Me O-n-dodecyl 4-8r 5-Cl CO2Me Me O-n-dodecyl 4-OC~3 5-Cl CO2Me Me O-n-dodecyl 4-CF3 5-Br CO2Me Me O-n-dodecyl 4-C1 5-~r CO2Me Me O-n-dodecyl 4-Br 5-Br CO2Me Me O-n-dodecyl 4-OCF3 5-~r CO2Me Me O-n-dodecyl 4-CF3 4-F CO2Me Me O-n-d~decyl 4-C1 4-F CO2Me Me O-n-dodecyl 4-Br 4-F CO2Me Me O-n-dodecyl 4-OCF3 4-F CO2Me Me O-n-dodecyl 4-CF3 5-CF3 CO2Me Me O-n-dodecyl - 4-CF3 5-F CO2Me Me O-n-dodecyl 4-CF3 5-Cl Ph Me O-n-dodecyl ; 20 4-CF3 5-C1 4-Cl-Ph Me O-n-dodecyl 4-CF3 5-Cl CO2Et . Me O-n-dodecyl 4-CF3 5-Cl Me Me O-sec-Bu 4-CF3 iH CO2Me Me O-sec-Bu . 9-Cl H CO2Me Me O-sec-Bu 4-Br H CO2P~e Me O-sec-Bu . 4-OCF3 H CO2Me Me O-sec-Bu 4-CF3 5-Cl CO2Me Me O-sec-Bu 4-C1 5-Cl CO2Me Me O-sec-Bu 4-Br 5-Cl CO2Me Me O-sec-Bu 4-OCF3 5-Cl CO2Me Me O-sec-Elu 4-CF3 5-Br CO2Me Me O-sec-Bu 4-C1 5-Br CO2Me Me O-~ec-Bu 4-Br 5-Br CO2Me Ne O-sec-Bu 4-OCF3 5-Elr CO2Me Me O-sec-Bu 4-CF3 4-F CO2Me Me O-sec-Bu 4-C1 4-F CO2Me Me O-sec-Bu , ,. . .
:, . , , . . . :
2~ 130 Rl R2 ~ R8 Rg 4-Br 4-F CO2Me Me ~-~ec-Bu 4-OCF34-F CO2Me Me O-sec-Bu 4-CF35-CF3 CO2Me Me O-sec-Bu 4-CF35-F CO2Me Me O-sec-~u 4-CF3 5-Cl Ph Me O-sec-~u 4-CF35-C14-Cl-Ph Me O-sec-Bu 4-CF3 5-Cl CO2Et Me O-sec-~u 4-CF35-Cl Me Me OCH2CH20Et . 4-CF3 H CO2Me Me OCH2CH20Et :~ 15 4-Cl H CO2Me Me OCH2CH20Et 4-Br H CO2Me Me OCH2CH20Et 4-OCF3 H CO2Me Me OCH2CH20Et .. 4-CF35-Cl CO2Me Me OCH2CH20Et `~ 4-C15-Cl c02Me Me OCH2CH20Et 2~ 4-~r 5-Cl CO2Me Me OCH2CH20Et 4-OCF35-Cl CO2Me Me OCH2CH20Et 4-CF35-Br CO2Me Me OCH2CH20Et 4-C15-Br CO2Me Me OCH2CH20Et 4-Br 5-Br CO2Me Me OCH2CH20Et 4-OCF35-Br CO2Me Me OCH2CH20Et . 4-CF34-F CO2Me Me OCH2CH20Et ` 4-C14-F ~2Me Me OCH2CH20Et ` 4-Br 4-F CO2Me Me OCH2CH20Et .~ 4-OCF34-F CO2Me Me OCH2CH20Et 4-CF3 S-CF3 C02Me Me OCH2CH20Et 4-CF35-F CO2Me Me OCHiCH20Et 4-CF3 5-Cl Ph Me OCH2CH20Et 4-CF3 5-C1 4-Cl-Ph Me OCH2CH20Et 4-CF35-Cl C02Et Me OCH2CH2~Et 4-CF35_Cl Me Me OCH2CC13 .. '! 4-CF3 H CO2Me Me OCH2CC13 4-Cl H CO2Me Me OCH2CC13 .~ 4-Br H CO2Me Me OCH2CC13 ~-':~
~,:
". ''.
,:
, ~ . ... . : . , . ~ :
Zt~(?c~130 .
1 R2 B R8 Rg 4-OCF3 H CO2Me Me OCH2CC1 4-CF3 5-Cl CO2Me Me OCH2CC1 4-C1 5-Cl C~2Me Me OCH2CC1 4-Br 5-Cl CO2Me Me OCH2CC1 4-OCF3 S-Cl CO2Me Me OCH2CC1 4-CF3 5-Br CO2Me Me OCH2CC1 4-C1 5-Br CO2Me Me OCH2CC1 4-Br 5-Br CO2Me Me OCH2CC1 4-OCF3 5-~r CO2Me Me OCH2CC1 4-CF3 4-F CO2Me Me OCH2CC1 4-C1 4-F CO2Me Me OCH2CC1 4-Br 4-F CO2Me Me OCH2CC1 4-OCF3 4-F CO2Me Me OCH2CC1 4-CF3 5-CF3 CO2Me Me OCH2CC1 4-CF3 5-F CO2Me Me OCH2CC1 - 4-CF3 5-Cl Ph Me OCH2CC1 4-CF3 5-C1 4-Cl-Ph Me OCH2CC1 4-CF3 5-Cl CO2Et Me OCH2CC1 4-CF3 5-Cl Me Me OCH2CF3 4-CF3 H CO2Me Ne OCH2CF3 .``~ 9-Cl H CO2Me Me OCH2CF3 4-Br H CO2Me Me OCH2CF3 -~ 4-OCF3 H CO2Me Me OCH2CF3 :- 4-CF3 5-Cl CO2Me ~e OCH2CF3 4-C1 5-Cl CO2Me Me OCH2CF3 4-Br 5-Cl CO2Me Me OCH2CF3 4-OCF3 5-Cl CO2Me Me OCH2CF3 4-CF3 5-~r CO2Me Me OCH2CF3 ; 4-Cl S-Br CO2Me Me OCH2CF3 : 35 4-Br 5-~r CO2Me Me OCH2CF3 4-OCF3 5-Br CO2Me Me OCH2CF3 :. ~
. . ~
:
2~ 30 .: '.-:
.. . .
1 R2 ~ R8 Rg ~ 4-CF34-F CO2Me Me OCH2CF3 : 4-C14-F CO2Me Me OCH2CF3 4-Br 4 F CO2Me Me OCH2CF3 9-OCF34-F CO2Me Me OCH2CF3 4-CF35-CF3 CO2Me Me OCH2CF3 4-CF35-F CO2Me Me OCH2CF3 ~ 4-CF35-Cl Ph Me OCH2CF3 :. 4-CF35-C14-Cl-Ph Me OCH2CF
4-CF35-Cl CO2Et Me OCH2CF3 :~ lS 4-CF35-Cl Me Me OCH2CO2Et 4-CF3 H CO2Me Me OCH2~O2Et 4-Cl H CO2Me Me OCH2CO2Et 4-Br H C2M~ Me OCH2CO2Et 4-OCF3 H CO2Me Me OCH2CO2Et ~ 20 4-CF35-Cl CO2Me Me OCH2CO2Et .~- 4-C15-Cl CO2Me Me OCH2CO2Et ~` 4-Br S-Cl CO2Me Me OCH2CO2Et 4-OCF35-Cl CO2Me Me OCH2CO2Et -, 4-CF35-Br CO2Me Me- OCH2CO2Et 4-Cl S-Br CO2Me Me OCH2CO2Et .~. 4-Br 5-8r CO2Me Me OCH2CO2Et 4-OCF35-Br CO2Me Me OCH2C2Et ~ 4-CF34-F CO2Me Me OCH2CO2Et .~ 4-C14-F CO2Me Me OCH2CO2Et 4 Br 4-F CO2Me Me OCH2CO2Et 4-OCF34-F CO2Me Me OCH2CO2Et . 4-CF35-CF3 CO2Me Me OCH2CO2Et 4-CF35-F CO2Me Me OCH2CO2Et 4-CF35-Cl Ph Me OCH2CO2Et 4-C~35-Cl 4-Cl-Ph Me OCH2CO2Et 4-CF35-Cl CO2Et Me OCM2COzEt :
, ;. - . . .
Z~Q0130 Rl R2 B R8 Rg 4-CF3 H H Me F
4-CF3 5-Cl H Me F
- 4-CF3 5-Br H Me F
4-CF3 4-F H Me F
4-CF3 H Me Me F
4-CF3 5-Cl Me Me F
. 4-CF3 5-Br Me Me F
4-CF3 4-F Me Me F
. 4-CF3 H CO2Me Me F
4-Cl H CO2Me Me F
4-Br H CO2Me Me F
4-OCF3 H CO2Me Me F
4-CF3 5-Cl CO2Me Me F : -~. 4-C1 5-Cl CO2Me Me :.: 20 4-Br 5-Cl CO2Me Me F
4-OCF3 5-Cl CO2Me Me F
. 4-CF3 5-~r CO2Me Me F
4-C1 5-Br CO2Me Me F
4-Br 5-Br CO2Me Me F
4-OCF3 5-Br CO2Me Me F
4-CF3 4-F ~O2Me Me F
4-C1 4-F CO2Me Me F
4-Br 4-F CO2Me Me F
4-OCF3 4-F CO2Me Me F
4-CF3 5-CF3 CO2Me Me F
4-CF3 5-F CO2Me Me F
~ 4-CF3 5-Cl Ph Me F
: 4-CF3 5-C1 4-Cl-Ph Me F
4-CF3 5-Cl CO2Et Me F
4-CF3 5-Cl CO2Me Me piperidino 4-CF3 4-F Me Me piperidino 4-CF3 Cl CO2Me Me morpholino .'' ' ~
"
~ :
Z~-~U0:130 .. .
.
Rl R2 B R8 Rg 4-OCF3 Cl CO2Me Me m~rph~lino 4-CF3 5-Cl CO2Me Me n-Pr 4-OCF3 5-Cl CO2Me Me n-Pr 4-CF3 5-Br CO2Me Me sec-~u 4-C1 5-Br CO2Me Me ~ec-Bu 4-Br 5-Br CO2Me Me sec-Bu ; 4-OCF3 5-Br CO2Me Me sec-Bu 4-CF3 4-F CO2Me Me 4-Cl-Ph 4-C1 4-F CO2Me Me 4-Cl-Ph 4-Br 4-F CO2Me Me 4-Cl-Ph 4-OCF3 4-F CO2Me Me 4-Cl-Ph 4-CF3 S-Cl Me Et OCH2CC13 4-CF3 H CO2Me Et NEt2 4-Cl H CO2Me Et NEt2 4-Br H CO2Me Et NEt2 4-OCF3 H CO2Me Et NEt2 .~ 4-CF3 5-Cl CO2Me Et 2,6-di-Me-morpholino :` 4-C1 5-Cl CO2Me Et 2,6-di-Me-morpholino . 4-Br S-Cl CO2Me Et 2,6-di-Me-morpholino .-~ 25 4-OCF3 5-Cl CO2Me Et 2,6-di-Me-morpholino `~:
.~, 4-CF3 5-Cl Me iPr OEt - 4-CF3 H CO2Me iPr OEt 4-Cl H CO2Me iPr OEt -~ 4-Br H CO2Me iPr OEt 4-OCF3 H CO2Me iPr OEt 4-CF3 5-Cl CO2Me iPr OEt --.
. 4-C1 5-Cl CO2Me iPr OEt ; 4-Br 5-Cl CO2Me iPr OEt 4-OCF3 5-Cl CO2Me iPr OEt 4-CF3 5-Br CO2Me iPr OEt 4-C1 5-Br CO2Me iPr OEt -~.
~',( ';
i , ' ' . ~ .
. .. ..
, . .
~,::; - : - .
. . . : . .. , - . . : .
- : . - . - - . ... ~ , .,. ~, , 2~ 130 Rl R2 B R~ Rg ' ~, ' .
4-Hr S-Br CO2Me iPr OEt 4-OCF35-Br C02Me iPr OEt 4-CF34-F CO2Me iPr OEt 4-C14-F CO2Me iPr OEt 1~ 4-Br 4-F CO2Me iPr OEt 4-OCF34-F CO2Me iPr OEt 4-CF35-CF3 co2Me iPr OEt 4-CF35-F CO2Me iPr OEt : 4-CF35-Cl Ph iPr OEt - 15 4-CF35-C14-Cl-Ph iPr OEt 4-CF3 S-Cl CO2Et iPr OEt 4-CF35-Cl CO2Me Me ON~(CH3)SCH3 . 4-CF35-Cl CO2Me Me 2,3-dihydro-2,2-dimethylbenzofuranyl ' ~Y-7 ~; 4-CF35-Cl CO2Me Me l-naphthosy : 4-CF35-Cl Me iPr O-n-Bu 4-CF3 ~ CO2Me iPr O-n-Bu . 4-Cl H CO2Me iPr O-n-Bu 4-Br H CO2Me iPr O-n-Bu , 4-OCF3 H CO2Me iPr O-n-Bu 4-CF35-Cl CO2Me iPr O-n-Bu :~. 4-C15-Cl CO2Me iPr O-n-Bu ~' . 4-Br 5-Cl CO2Me iPr O-n-Bu : 30 4-OCF35-Cl CO~Me iPr O-n-Bu 4-CF35-Br CO2Me iPr O-n-Bu.
4-C~ 5-Br CO2Me iPr O-n-Bu 4-Br 5-Br CO2Me iPr O-n-Bu 4-OCF35-Br C2~e iPr O-n-Bu 4-CF34-F CO2Me iPr O-n-Bu ~ 4-C14-F CO2Me iPr O-n-Bu : .
4-Br 4-F CO2Me iPr O-n-Bu ~. . .
,"
2a~i31~
Rl R2 B R8 Rg .
4-OCF3 4-F ~O2Me iPr O-n-Bu 4-CF3 5-CF3 CO2Me iPr ~-n-Bu 4-CF3 5-F CO2Me iPr O-n-Bu 4-CE3 5-Cl Ph iPr O-n-~u 4-CF3 5-C1 4-Cl-Ph iPr O-n-Bu 4-CF3 S-Cl CO2Et iPr O-n-Bu 4-CF3 H CO2Me iPr OCH2CO2Me . 4-CF3 5-Cl CO2Me iPr OCH2CO2Me t 4-CF3 5-Br CO2Me iPr OCH2CO2Me : 15 4-CF3 4-F CO2Me iPr OCH2CO2Me 4-CF3 H CO2Me iPr NMe2 4-Cl H CO2Me iPr NMe2 ~: 4-~r H CO2Me iPr NMe2 4-OCF3 H CO2Me iPr NMe2 ~; 20 4-CF3 5-Cl CO2Me iPr NEt2 4-C1 5-Cl CO2Me iPr NEt2 4-Br 5-Cl CO2Me iPr NEt2 4-OCF3 5-Cl C~2Me iPr NEt2 4-CF3 5-Br CO2Me iPr piperidino :~
4-C1 5-Br CO2Me iPr piperidino . 4-~r 5-Br CO2Me iPr piperidino ~`
4-OCF3 5-~r CO2Me iPr piperidino 4-CF3 4-F CO2Me iPr Et : 4-C1 4-F CO2Me iPr Et 4-Br 4-F CO2Me iPr Et 4-OCF3 4-F CO~Me iPr Et 4-CE3 H H CH2Ph OEt 4-CF3 5-Cl H CH2Ph O-n-octyl 4-CF3 5-Br H CH2Ph OCH2CO2Et 4-CF3 H Me CH2Ph NEt2 ', .
."
, ~ .
... .
: . :
' ~
~ .
'` ~ ' ' -' ' . :'` ' ' ' ' ' .,` ' '~ ' ' 2~ 0130 Rl R2 ~ R8 Rg 4-CF3 5-Cl he CH2Ph morpholino 4-CF3 5-Br Me. CH2Ph 4-Cl-Ph : 4-CF3 4-F Me CH2Ph Et 4-CF3 H CO2Me CH2Ph O-n-Bu 4-Cl ~ CO2Me CH2Ph O-iPr 4-Br H CO2Me CH2P~ OCH2CF3 4-OCF3 H CO2Me CH2Ph NMe2 q-CF3 5-Cl CO2Me CH2Ph piperidino 4-C1 5-Cl CO2Me CH2Ph Ph lS 4-Br 5-Cl CO2Me CH2Ph 4-NO2-Ph : 9-OCF3 5-Cl CO2Me CH2Ph ~u 4-CF3 5-Br CO2Me CH2Ph O-n-he~yl ~ 4-C1 5-Br CO2Me CH2Ph O-sec-Bu `: 9-Br S-Br CO2Me CH2Ph OCH2CH20Et :............ 2~ 4-OCF3 5-Br CO2Me CH2Ph NMe2 4-CF3 4-F CO2Me CH2Ph 2,6-di-Me-morpholino 4-C1 4-F CO2Me CH2Ph 3-Br-Ph 4-Br 4-F CO2Me CH2Ph 4-Me-Ph ^ 4-OCF3 4-F CO2Me CH2Ph nPr 4-CF3 5-CF3 CO2Me CH2Ph Me 4-CF3 5-F CO2Me CH2Ph OEt .' 4-CF3 5-Cl Ph CH2Ph O-n-Bu 4-CF3 5-C1 4-Cl-Ph CH2Ph O-n-octyl 4-CF3 5-Cl C02Et CH2Ph OCH2ccl3 -: .:
. .
... ..
^: 35 . ~ , .'. .
. . .:
:~' , - .'~ :. ,.
2"~ L3~
::
' ~' : 5 -:' .
4 , ..
N~ R~
:. ~N d~
:~ S-N-S-R~
: .
.
l _ R2 B R8 Rg s 9-CF3 H CO2Me Me NMe2 4-Cl H CO2Me Me NMe2 4-Br H CO2Me Me NMe2 4-OCF3 H CO2Me Me NMe2 4-CF3 5-Cl CO2Me Me NMe2 4-C1 5-Cl CO2Me Me NMe2 -:~ 4-Br 5-Cl . CO2Me Me NMe2 4-OCF3 5-Cl CO2Me Me NMe2 ,. 30 4-CF3 5-Br CO2Me Me NMe2 4-C1 5-Hr CO2Me Me NMe2 ;-. 4-Br S-Br CO2Me Me NMe2 ;~ 4-OCF3.5-Br CO2Me Me NMe2 4-CF3 4-F CO2Me Me NMe2 ;. 35 4-C1 4-F CO2Me Me NMe2 . ., , ~ .
;
-~
~ .
.. . .
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2'~QQ130 : - 57 Rl R2 E~ R8 Rg 5 .
4-~r 4-F CO2Me Me NMe2 4-OCF3 4-F CO2Me Me NMe2 4-CF3 5-CF3 CO2Me Me NMe2 4-C~3 5-F CO2Me Me NMe2 : 104-CF3 5-Cl Ph Me NMe2 ~:. 4-CF3 5-C1 4-Cl-Ph Me NMe2 4-CF3 5-Cl CO2Et Me NMe2 : 9-CF3 H CO2Me Me NEt2 -~ 4-Cl H CO2Me Me NEt2 !~:-15 9-Br H CO2Me Me NEt2 4-OCF3 H CO2Me Me NEt2 -CF3 5-Cl CO2Me Me NEt2 4-C1 5-Cl CO2Me Me NEt2 4-Br 5-Cl CO2Me Me NEt2 204-OCF3 5-Cl CO2Me Me NEt2 4-CF3 5-8r CO2Me Me NEt2 4-C1 5-Br CO2Me Me NEt2 - 4-Br 5-Br CO2Me Me NEt2 4-OCF3 5-Br CO2Me Me NEt2 4-CF3 4-F CO2Me Me NEt2 :~, 4-C1 4-F CO2Me Me piperidino . 4-BI 4-F CO2Me Me piperidino ;. 4-OCF3 4-F CO2Me Me piperidino .. 4-CF3 5-CF3 CO2Me Me piperidino . 304-CF3 5-F CO2Me Me piperidino 4-CF3 5-Cl Ph Me piperidino . 4-CF3 !5-C1 4-Cl-Ph Me piperidino 4-CF3 S-Cl CO2Et Me piperidino 4-CF3 H CO2Me Me C2H5 354-CF3 5-Cl CO2Me Me C2H5 ~ ~::
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4-CF3 5-Cl CO2Me Me Ph 4-C1 5-Cl CO2Me Me Ph 4-Br S-Cl CO2Me Me Ph 4-OCF3 5-Cl CO2Me Me Ph 4-CF3 5-Br CO2Me Me 4-Cl-Ph 4-C1 5-Br CO2Me Me 4-Cl-Ph 4-Br 5-Br CO2Me Me 4-Cl-Ph 4-OCF3 5-Br CO2Me Me 4-Cl-Ph 4-CP3 9-F CO2Me Me 4-Me-Ph ;~ 4-C1 4-F CO2Me Me 4-Me-Ph ;:
. 20 4-Br 4-F CO2Me Me 4-Me-Ph 4-OCF3 4-F CO2Me Me 4-Me-Ph 4-CF3 5-CF3 CO2Me Me n-Bu 4-CF3 5-F CO2Me Me n-Bu ` 4-CF3 5-Cl Ph Me n-Bu " . 25 4-CF3 5-C1 4-Cl-Ph Me n-13u 4-CE3 5-Cl CO2Et Me n-Bu . 4-CF3 H H Et NMe2 ., 4-CF3 5-Cl H Et NMe2 4-CF3 5-Br H Et NMe2 3~ 4-CF3 4-F H Et NMe2 . 4-CF3 H Me Et NEt2 4-CF3 5-Cl Ne Et NEt2 .` 4-CF3 5-Br Me Et NEt2 4-CF3 4-F Me Et NEt2 . 35 4-CF3 5-Cl CO2Me Et morpholino 4-C1 5-Cl CO2Me Et morpholino 4-Br 5-Cl CO2Me Et morpholino 4-OCF3 5-C1 ~02Me Et morpholino . .
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9-CF35-Cl CO2Me Et iPr 4-C1 5-Cl CO2Me Et iPr 4-Br 5-Cl CO2Me Et iPr 4-OCF3 5-Cl CO2Me Et iPr 10 4-CF3 5-ESr CO2Me Et n-Bu 4-C1 5-~r CO2Me Et n-Bu 4-Br 5-Br CO2Me Et n-Bu ~4-OCF3 5-Br CO2Me Et n-~u 4-CF3 4-F CO2Me Et Ph . 15 4-C1 4-F CO2Me Et Ph - 4-Br 4-F CO2Me Et Ph 4-OCF3 4-F CO2Me Et Ph 4-CF3 H CO2Me i Pr NMe2 4-Cl H CO2Me iPr NMe2 20 4-Br H CO2Me iPr NMe2 4-OCF3 H CO2Me i Pr NMe2 4-CF3 5-Cl CO2Me iPr NMe2 ` 4-C1 5-Cl CO2Me iPr NMe2 1~ 4-Br 5-Cl CO2Me iPr NMe2 -` 25 4-OCF3 5-Cl CO2Me iPr NMe2 -~ 4-CF3 5-Br CO2Me iPr NMe2 4-C1 5-Br CO2Me iPr NMe2 ' 4-Br 5-Br CO2Me iPr NMe2 ' . 4-OCF3 5-Br CO2Me iPr NMe2 - 30 4-C~3 4-F CO2Me iPr NMe2 4-C1 4-F CO2Me iPr NMe2 4-Br 4-F CO2Me iPr NMe2 ; 4-OCF3 4-F CO2Me iPr NMe2 4-CF3 5-CF3 C2 iPr NMe2 ' 35 4-CF3 5-F C2M~ iPr NMe2 4-CF3 5-Cl Ph iPr NMe2 4-CF3 5-C1 4-Cl-Ph iPr NMe2 4-CF3 5-Cl CO2Et iPr NMe2 '~',, ;
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Z'~Q~130 . Rl R2 B RB Rg :' . , : 4-CF3 H ~O2Me iPr 2,6-di-Me-morpholino 4-CF3 5-Cl CO2Me iPr 2,6-di-Me-m~rpholino 4-CF3 5-Br CO2Me iPr 2,6-di-Me-morpholino 4-CF3 4-F CO2Me iPr 2,6-di-Me-morpholino 4-CF3 H CO2Me iPr piperidino : 4-OCF3 H CO2Me iPr piperidino 4-CF3 5-Cl CO2Me iPr Et 4-C1 5-Cl CO2Me iPr Et 4-Br 5-Cl CO2Me iPr Et : 15 4-OCF3 5-Cl CO2Me iPr Et q-CF3 5-Br CO2Me iPr n-Bu ;.~ 4-C1 5-Br CO2Me iPr n-Bu : 4-Br 5-Br CO2Me iPr n-Bu 4-OCF3 5-Br CO2Me iPr n-Bu ; 20 4-CF3 4-F CO2Me iPr Ph .~~ .
'. 4-C1 4-F CO2Me iPr Ph 4-Br 4-F CO2Me iPr Ph ~: 4-OCF3 4-F CO2Me iPr Ph -~ 4-CF3 5-CF3 CO2Me iPr 4-Cl-Ph . 25 4-CF3 5-F CO2Me iPr 4-Cl-Ph 4-CF3 5-Cl Ph iPr 4-Cl-Ph '~ 4-CF3 5-C1 4-Cl-Ph iPr 4-Cl-Ph -~
4-CF3 5-Cl C~2Et iPr 4-Cl-Ph .
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4-CF3 H CO2Me tBu S OEt OEt 4-Cl H CO2Me t~u S OEt OEt 4-Br H CO2Me tBu S OEt OEt 4-OCF3 H CO2Me tBu S OEt OEt 4-CF3 S-Cl CO2Me tBu S OEt OEt `~; 4-Cl S-Cl CO2Me tBu S OEt OEt 4-Br S-Cl CO2Me tBu S OEt OEt ., 4-OCF3 5-Cl CO2Me tBu S OEt OEt ` 4-CF3 S-Br CO2Me tBu S OEt OEt ~; 4-C1 5-Br CO2Me tBu S OEt OEt 4-Br 5-Br CO~Me tBu S OEt OEt 4-OCF3 S-Br CO2Me tBu S OEt OEt 4-CF3 4-F CO2Me tBu S OEt OEt 4-C1 4-F CO2Me tBu S ~ OEt OEt 9-Br 4-F CO2Me tBu S OEt OEt ~` 4-OCF3 4-F CO2Me tBu S OEt . OEt 4-CF3 5-CF3 CO2Me tBu S OEt OEt 4-CF3 5-F CO2Me tBu S OEt OEt 4-CF3 S-Cl Ph tBu S OEt OEt .,' ~.
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10 4-Cl H CO2Me tBu S OCH2C(Me)2CH2o 4-Br H CO2Me tBu S OCH2C(Me)2CH20 4-OCF3 H C02Me tBu S OCH2C(Me)2CH20 : 4-CF3 5-Cl CO2Me t8u S OCH2C(Me)2CH20 4-C1 5-Cl CO2Me tBu S OCH2C(Me)2cH2o 15 4-Br 5-Cl CO~Me tBu S OCH2c(Me)2cH20 4-OCF3 5-Cl CO2Me tBu S OCH2C(Me~2CH20 4-CF3 5-Br CO2Me tBu S OCH2C(Me)2CH20 4-C1 5-Br CO2Me tBu S OCH2c~Me)2cH20 4-Br 5-Br CO2Me tBu S OCH2c(Me~2cH20 2~ 4-OCF3 5-Br CO2Me tBu S OCH2c~Me)2c~20 : 4-CF3 4-F CO2Me tBu S OCH2C(Me)2cH2o 9-C1 4-F CO2Me tBu S OCH2C~Me)2c~20 4-Br 4-F CO2Me tBu S OCH2C~Me)2CH20 4-OCF3 4-~ CO2Me tBu S OCH2C~Me)2CH20 25 ~-CF3 5-CF3 CO2Me tBu S OCH2c(Me)2cH20 4-CF3 5-F ~2Me t~u S OCH2c(Me)2cH20 i 4-CF3 5-Cl Ph tBu S OCH2C(Me)2cH2o 4-CF3 5-C1 4-Cl-Ph t9u S OCH2c(Me~2cH20 4-CF3 5-Cl CO2Et tBu S OCH2c(Me)2cH20 30 4-CF3 H CO2Me tBu S OCH2CH2CH20 4-C~ ~ C2~e tBu S OCH2CH2CH20 4-Br H CO2Me tBu S OCH2CH2CH20 4-OCF3 H CO2Me t~u S OCH2CH2CH20 4-CP~ 5-Cl CO2Me t~u S OCH2CH2CH20 35 4-Cl S-Cl CO2Me tBu S OCH2CH2CH20 4-Br 5-Cl CO2Me tBu S OCH2CH2CH20 4-OCF3 5-Cl CO2Me tBu S CH2CH2CH20 ~ ' ' ~, .
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5 1 R2 B R~ Y' Y'Rlo Y Rll 4-CF3 5-Br CO2Me tBu S OcH2cH2cH2o 4-C1 5-Br CO2Me tBu S OCH2CH2CH2o 4-Br 5-Br CO2Me tBu S OCH2CH2CH2O - ~.
4-OCF3 5-Br CO2Me tBu S OcH2cH2cH2o .
4-CF3 4-F CO2Me tBu S OCH2CH2CH2O . .
4-C1 4-F CO2Me t~u ~ OCH2CH2CH2 ~ .
4-Br 4-F CO2Me tBu S OCH2CH2CH2 4-OCF3 4-F CO2Me tBu S OCH2CH2CH2O
4-CF3 5-CF3 CO2Me tBu OCH2CH2CH2 4-CF3 5-F CO2Me tBu S OCH2CH2CH2O :.
4-CF3 S-Cl Ph tBu S OCH2CH2CH2 4-CF3 5-C1 4-Cl-Ph tBu S OCH2cH2cH2O
4-CF3 5-Cl CO2Et tBu S OCH2CH2CH2O .
4-CF3 H CO2Me tBu S OCHzCH2O
4-Cl H CO2Me tBu S OCH2CH2O
4-Br H CO2Me tBu S OCH2CH2 4-OCF3 H CO2Me tBu S OCH2CH2O .
; 4-CF3 5-Cl CO2Me tBu S OCH2CH2 ~- 254-C1 5-Cl CO2Me tBu S OCH2CH2O :;
9-Br S-Cl CO2Me tBu S OCH2CH2O
4-OCF3 5-Cl CO2Me tBu S OCH2CH2O '.
4-CF3 5-~r CO2Me tBu S OCH2CH2O
, 4-C1 5-Br CO2Me tBu S OCH2CH2O . .
- 304-Br 5-Br CO2Me tBu S OCH2CH2O .~
4-OCF3 5-Br CO2Me tBu S OCH2CH2O ::
4-CF3 4-F CO2Me tBu S OCH2CH2O
4-C1 4-F CO2Me tBu S OCH2CH2 4-Br 4-F CO2Me tBu S OCH2CH2 4-OCF3 4-F CO2Me tBu S OCH2CH2O
. 4-CF3 5-CF3 CO2Me tBu S OCH2CH2 4-CF3 5-F CO2Me tBu S OCH2CH2O
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4-CF3 5-Cl Ph tBu S Q2CH2O
4-CF3 S-Cl 4-Cl-Ph tBu S ~H2C~2 4-CP3 5-Cl CO2Et tBu S CH2cH2 4-CF3 H CO2Me iPr S OEt OEt :~ 4-Cl H CO2Me . iPr ~ OEt OEt 4-Br H CO2Me iPr S OEt OEt 4-OCF3 H ~O2Me iPr S OEt OEt 4-CF3 5-Cl CO2Me iPr S OEt OEt ~ lS 4-C1 5-Cl CO2Me iPr S OEt OEt - 4-Br 5-Cl CO2Me iPr S OEt OEt 4-OCF3 S-Cl CO2Me iPr S OEt OEt 4-CF3 5-~r CO2Me iPr S OEt OEt 4-Cl S-Br CO2Me iPr S OEt OEt 4-Br 5-Br CO2Me iPr S O~t OEt :~ 4-OCF3 5-Br CO2Me iPr S OEt OEt 4-CF3 4-F CO2Me iPr S OEt OEt , . . .
4-C1 4-F CO2Me iPr S OEt OEt ~ 9-Br 4-F CO2Me iPr S OEt OEt ; 25 4-OCF3 4-F CO2Me iPr S OEt OEt.
4-CF3 5-CF3 CO2Me iPr S OEt OEt 4-CF3 S-F CO2Me iPr S OEt OEt 4-CF3 5-Cl Ph iPr S OEt OEt 9-CF3 5-C1 4-CI-Ph iPr S OEt OEt 3C 4-CF3 5-Cl CO2Et iPr S OEt OEt 4-CF3 H CO2Me iPr S OCH2c~Me~2cH2 4-Cl H CO2Me iPr S OCH2C~Me)2cH2O
4-Rr H CO2Me iPr S OCH2C(Me)2cH2O
4-OCF3 H .C02Me iPr S OcH2c(Me)2cH2o 4-CF3 S-Cl CO2Me iPr S OcH2c(Me)2c~2o 4-C1 5-Cl CO2Me iPr S OCH2c(Me)2cH2O
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4-Br 5-Cl CO2Me iPr 5 OcH2c(Me)2cH2o 4-OCF3 5-Cl CO2Me iPr S OCH2C(Me)2CH2o 4-CF3 5-Br CO2Me iPr S OCH2c(Me)2cH2O
4-C1 5-Br CO2Me iPr S OCH2C(Me)2CH2O
4-~r 5-Hr CO2Me iPr S OCH2C(Me)2CH2O
4-OCF3 5-Qr CO2Me iPr S OCHzC(Me)2CH2O
4-CF3 4-F CO2Me iPr S OCH2C(Me)2cH2o 4-C1 4-F CO2Me iPr S OCH2C(Me)2cH2o ; 15 4-~r 4-F CO2Me iPr S OCH2C(Me)2CH2O
4-OCF3 4-F CO2Me iPr S OCH2C(Me)2CH2O
4-CF3 S-CF3 CO2Me iPr S OCH2C(Me)2CH2O
4-CF3 5-F CO2Me iPr S OCH2C(Me)2CH2O ..
4-CF3 5-Cl Ph iPr S OCH2c(Me)2cH2O
~. 20 4-CF3 5-C1 4--Cl-Ph iPr S OCH2C(Me)2CH2O
:~ 4-CF3 5-Cl CO2Et iPr S OCH2CtMe)2CH2O ~-4-CF3 H CO2Me Me S OEt OEt 4-Cl H CO2Me Me S OEt OEt .. 4-Br H CO2Me Me S OEt OEt '?`: 25 4-OCF3 H CO2Me Me S OEt OEt 4-CF3 5-Cl CO2Me Me æ OEt OEt .. 4-C1 5-Cl CO2Me Me S OEt OEt ~ 4-Br 5-Cl CO2Me Me S OEt OEt ,'~ . 4-OCF3 5-Cl CO2Me Me S OEt OEt -: 30 4-CF3 5-Br CO2Me Me S OEt OEt : 4-C1 5-Br CO2Me Me S . OEt OEt ;.
4-Br 5-Br CO2Me Me S OEt OEt `
4-OCF3 5-Br C02Me Me S OEt OEt 4-CF3 4-F CO2Me Me S OEtOEt . ~:
:~- 35 4-C1 4-F CO2Me Me S OEt OEt 4-Br 4-F CO2Me Me S OEt OEt :
4-OCF3 4-F CO2Me Me S OEt OEt 4-CF3 5-CF3 co2Me Me S OE:tOEt ` .
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4-CF35-F CO2Me Me S OEt OEt 4-CF3 S-Cl Ph Me S OEt OEt 4-CF35-C14-Cl-Ph Me S OEt OEt 4-CF3 H CO2Me tBu o OEt OEt 4-Cl H CO2Me tBu O OEt OEt q-Br H CO2Me tBu O OEt OEt ; 4-OCF3 H CO2Me tBu O OEt OEt .
4-CF35-Cl C02Me tBu O OEt OEt 4-C15-Cl CO2Me tBu O OEt OEt ; 4-Br S-Cl CO2Me tBu O OEt OEt g-OCF35-Cl CO2Me tBu O OEt OEt 4-CF35-Br CO2Me tBu O OEt OEt 4-C15-Br CO2Me tBu O OEt OEt 4-Br 5-Br CO2Me tBu O OEt OEt 4-OCF35-Br CO2Me tBu o OEt OEt 4-CF34-F CO2Me tBu O OEt OEt 4-C14-F CO2Me tBu O OEt OEt . 4-Br 4-F C02Me tBu O OEt OEt 4-OC~34-~ CO2Me $Bu O OEt OEt 4-CF35-CF3 CO~Me tBu O OEt OEt 4-CF35-F CO2Me tBu O OEt OEt 4-C~3 ~-Cl Ph tBu O OEt OEt 4-CF35-C14-Cl-Ph tBu O OEt OEt -~
4-CF35-Cl C~2Et tBu O OEt OEt 4-CF3 H CO2Me tBu O OCH2C~Me)2CH2~
; 4-CI H CO2Me tBu O OCH2C~Me)2CH20 :
~, 4-Br ~ CO2Me tBu O OCH2C(Me)2 Q2 4-OCF3 H CO2Me tBu O ocH2c(Me)2Q2o 4-CF35-Cl CO2Me tBu o OCH2C~Me)2cH2O
~ 4-Cl S-Cl C02Me tBu o OCH2C(Me)2cH2O
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9-Br 5-Cl CO2Me tBu ~ OCH2C(Me~2CH20 - 4-OCF3 5-Cl CO2Me tBu O OCH2CtMe)2CH2o 4-CF3 5-Br CO2Me tBu O OCH2C(Me)2CH2O
: 10 4-C1 5-Br CO2Me tBu O OCH2C(Me)2CH2O
4-Br 5-Br CO2Me tBu O OCH2C(Me)2CH2O
4-OCF3 S-Br CO2Me tBu O OCH2C(Me)2CH2O
: 9-CF3 4-F CO2Me tBu O OCH2C(Me)2cH2o 4-C1 4-F CO2Me tBu O OCH2C(Me)2CH2O
9-Br 4-F CO2Me tBu O OCH2C(Me)2cH2o 4-OCF3 4-F CO2Me tBu O OCHzC(Me)zCH2O
4-CF3 5-CF3 CO2Me tBu O OCH2C(Me)2cH2o : 4-CF3 5-F CO2Me tBu O OCH2C(Me)2cH2o . 4-CF3 5-Cl Ph tBu O OCH2C(Me)2CH2O
4-CF3 5-C1 4-Cl-Ph tBu O OCH2C(Me)2cH2o ,~ 4-CF3 5-Cl CO2Et tBu O OCH2C(Me)2cH2o 'J ~,;
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4-C1 4-F CO2Me iPr O Et OEt 4-Br 4-F CO2Me iPr O Et OEt 4-OCF3 4-F CO2Me iPr O Et OEt 4-CF3 5-CF3 CO2Me iPr O Et OEt 4-CF3 S-~ CO2Me iPr O Et OEt ~ 4-CF3 5-Cl Ph iPr O Et . OEt ; 4-CF3 5-C1 4-Cl-Ph iPr O Et OEt 4-CF3 5-Cl CO2Et iPr O Et OEt 4-CF3 H CO2Me iPr O Et O-iPr : 15 4-Cl H CO2Me iPr O Et O-iPr :
"` 4-~r H CO2Me iPr O Et O-iPr .. 4-OCF3 H CO2Me iPr O Et O-iPr . 4-CF3 5-Cl CO2Me iPr O Et O-iPr 4-Cl S-Cl CO2Me iPr O Et O-iPr :
`:- 4-Br 5-Cl CO2Me iPr O Et o-iPr 4-OCF3 5-Cl CO2Me iPr O Et O-iPr :~
` 4-CF3 5-Br CO2Me iPr O Et O-iPr `~ 4-C1 5-Br CO2Me iPr O Et O-iPr .`~ 4-8r 5-8r CO2Me iPr O Et O-iPr 25 9-OCF3 5-Br CO2Me iPr O Et o-iPr - 4-CF3 4-F CO2Me iPr O Et O-iPr 4-C1 4-F CO2Me iPr O Et O-iPr 4-Br 4-F CO2Me iPr O Et O-iPr 4-OCF3 4-F CO2Me iPr O Et O-iPr . 30 4-CF3 5-CF3 CO2Me iPr O Et o-iPr . 4-CF3 5-F C2M~ iPr O Et O-iPr 4-CF3 5-Cl Ph iPr O Et O-iPr 4-CF3 S-Cl 4-Cl-Ph iPr O Et O-iPr 4-CF3 S-Cl CO2Et iPr O Et O-iPr 35 4-CF3 H CO2Me iPr O Et OPh 4-Cl H CO2Me iPr O Et OPh ~" .
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4-Br H CO2Me iPr O Et . OPh 4-OCF~ H C02Me iPr O Et OPh 4-CF3 5-Cl CO2Me iPr O Et OPh 4-C1 5-Cl CO2Me iPr O Et OPh 4-Br 5-Cl CO2Me iPr O Et OPh 4-OCF3 5-Cl CO2Me iPr O Et OPh 4-CF3 S-~r CO2Me iPr O Et OPh 4-Cl S-Br CO2Me iPr O Et OPh 4-Br 5-Br CO2Me iPr O Et OPh 4-OCF3 5-Br CO2Me iPr O Et OPh 4-CF3 4~~ CO2Me iPr O Et OPh 4-C1 4-F CO2Me iPr O Et OPh ~-~ 9-Br 4-F CO2Me iPr O Et OPh 4-OCF3 4-F CO2Me iPr O Et OPh 4-CF3 5-CF3 CO2Me iPr O Et OPh . 4-CF3 S-P CO2Me iPr O Et OPh 4-CF3 5-Cl Ph iPr O Et OPh 4-CF3 5-C1 4-Cl-Ph iPr O Et OPh 4-CF3 5-Cl CO2Et iPr O Et OPh . 2~ 4-Br 4-F CO2Me iPr O Ph OEt 4-OCF3 4-F CO2Me iPr O Ph OEt ~` 4-CF3 5-CF3 CO2Me iPr O Ph OEt 4-CF3 5-F CO2Me iPr O Ph OEt 4-CF3 5-Cl Ph iPr O Ph OEt 4-C~3 S-Cl 4-Cl-Ph iPr O Ph OEt 4-CF3 5-Cl CO2Et iPr O Ph OEt ~ 4-CF3 H CO2Me tBu O Et OEt : 4-Cl H CO2Me tBu O Et OEt 4-Br H CO2Me tBu O Et OEt 4-OCF3 H CO2Me tBu O Et OEt 4-CF3 5-Cl C~2Me tBu O Et OEt 4-C1 5-Cl CO2Me tBu O Et OEt ., ' ~''~'~
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21~ ~0'~30 ` R R2 B R8 Y' Rlo Y Rll 9-Br 5-Cl CO2Me tBu O Et OEt 4-OCF3 5-Cl CO2Me tBu O Et OEt 4-CF3 5-Br CO2Me tBu O Et OEt ::: 4-Cl S-E~r C02Me tBu O Et OEt 4-Bs 5-Br COzMe tBu O Et OEt 4-OCF3 5-Br C02Me tE~u O Et OEt 4-CF3 4-F CO2Me tBu O Et OEt 4-C1 4-F C02Me tBu O Et OEt 4-E~r 9-F C02Me tBu O Et OEt :~ 15 4-OCF3 4-F CO2Me tBu O Et OEt 4-CF3 5-CF3 CO2Me tBu O Et OEt 4-CF3 5-F CO2Me tBu O Et OEt 9-CF3 5-Cl Ph tBu O Et OEt 4-CF3 5-C1 4-Cl-Ph tBu O Et OEt 20 4-CF3 5-Cl CO2Et tBu O Et OEt 4-CF3 H CO2Me tBu O Et O-iPr 4-Cl H CO2Me tBu O Et O-iPr . 4-Br H CO2Me tBu O Et O-iPr ; 4-OCF3 H CO2Me tBu O Et O-iPr 25 4-CF3 5-C1 CO2Me tBu O Et O-iPr 4-C1 5-Cl CO2Me tBu O Et O-iPr 4-Br 5-Cl CO2Me tBu O Et O-iPr 4-OCF3 5-Cl CO2Me tBu O Et O-iPr 4-CF3 5-Br CO2Me tBu O Et O-iPr 5-Br CO2Me tBu O Et O-iPr . 4-Br 5-Br CO2Me tBu O Et O-iPr 4-OCF3 5-Br CO2Me tBu O Et O-iPr 4-CF3 4-F CO2Me tBu O Et O-iPr 4-C1 4-F CO2Me tBu O Et O-iPr .` 35 4 Br 4-F CO2Me tBu O Et O-i~r - 4-OCF3 4-F C02Me tE~u O Et O-iPr 4-CF3 5-CF3 CO2Me tBu O Et O-iPr 4-CF3 5-F CO2Me tBu O Et O-iPr ., .''. .
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24~00130 . Rl R2 BR& Y' Rlo Y Rll .__ 4-CF3 5-Cl Ph t~u O Et O-iPr 9-CF3 5-C1 4-Cl-Ph tBu O Et O-iPr 4-CF3 5-Cl CO2Et tBu O Et O-iPr 4-CF3 H CO2Me tBu S Et OPh 4-Cl H CO2Me tBu S Ph OEt : 4-Br H CO2Me tBu S Ph O-iPr 4-OCF3 H CO2Me tBu S Ph OPh 4-Br 5-Br CO2Me iPr S iPr OEt 4-OCF3 5-Br CO2Me iPr S iPr O-iPr 4-CF3 4-F CO2Me iPr S iPr OPh 4-Cl 9-F CO2Me iPr S nPr OEt 4-Br 4-F CO2Me iPr S nPr O-iPr 4-OCF3 4-F CO2Me iPr S nPr OPh . 4-CF3 5-CF3 CO2Me tBu S Me OEt 4-CF3 5-F CO2Me tBu S Me O-iPr 4-CF3 5-Cl Ph t9u S Me OPh 4-CF3 5-C1 4-Cl-Ph tBu S Me O-sec-Bu 4-CF3 5-Cl CO2Et tBu S Me O-nPr .
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1 R2 B Rlo 11_ . 4-CF3 ~ CO2Me Et Et 4-Cl H CO2Me Et Et `' 4-Br H CO2Me Et Et , 4-OCF3 ~ CO2Me Et Et ;, 4-CF3 5-Cl CO2Me Et Et . 4-C1 5-Cl CO2Me Et Et 4-Br 5-Cl CO2Me Et Et 4-OCF3 5-Cl CO2Me Et Et ~ 4-CF3 5-Br CO2Me Et Et ;~ 4-C1 5-Br CO2Me Et Et !~
4-8r 5-8r CO~Me Et Et 4-OCF3 5-Br CO2Me Et Et 4-F C~2Me Et Et . ~ , .
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Rl R2 El Rlo Rll 4-C1 4-F CO2Me Et Et 4-Br 4-F CO2Me Et Et 4-OCF3 4-F CO2Me ~t ~t 4-CF3 5-CF3 C2Me Et ~t q-CF3 5-~ CO2Me Et ~t J-CF3 5-Cl Ph Et ~t 4-CF3 5-Cl q-Cl-Ph ~t Et ~ 4-CF3 5-CI CO2Et Et Et : 4-CF3 5-Cl Ph Ph Ph .. 15 4-CF3 5-C1 4-Cl-Ph Ph Ph 4-CF3 5-Cl C2Et Ph Ph :
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~: 20 .` Rl R2 B R~ R12 . _ ~ 4-CF3 ~ CO2Me nBu nBu '~ 4-Cl H CO2Me nBu nBu :~ . 25 4-Br H CO2Me nBu nBu 4-OCF3 H CO2Me nBu nBu . 4-CF3 5-CI CO2Me nBu nBu . 4-C1 5-Cl CO2Me nBu DBu ..
4-Br 5-Cl CO2Me nBu nBu ~` 30 4-OCF3 5-CI CO2Me nBu nBu .
~ 4-CF3 5-Br C02Me nBu ~Bu ,~ 4-C1 5-Br CO2Me nBu ~8u 4-Br 5-Br C02Me ~9u n8u 4-OCF3 5-Br C2~e nBu nBu . 35 4-CF3 4-F CO2Me nBu nBu -'; ' ' ~' ~
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2~001 30 Rl R2 ~ R8 R12 5 .
4-C1 4-F CO2MenBu DBu 4-Br 4-F CO2MeD~U DBU
4-OCF3 4-F CO2MenBu nBu 4-CF3 5-CF3 CO2Me nBu nBu 4 CF3 5-F CO2Me DBU nBu 4-CF3 5-Cl Ph nBu DBu 4-CF3 5-Cl q-Cl-Ph ~Bu DBu 4-CF3 5-Cl C02EtD}IU ~Bu . 4-CF3 H CO2Me-CH2CH2C~2cH2cH2-.:. 15 4-Cl H CO2Me-CH2CH2CH2cH2cH2-4-Br H CO2Me-CH2CH2CH2cH2cH2-4-OCF3 H C02Me-CH2CH2C~2cH2cH2-: 4-CF3 5-Cl CO2Me-CH2CH2CH2cH2cH2-4-C1 5-Cl CO2Me-CH2CH2CH2cH2cH2 .: 2 0 4-Br 5-Cl CO2Me-CH2CH2CH2cH2cH2-. 4-OCF3 5-Cl CO2Me-CH2CH2CH2cH2cH2-4-CF3 5-Br CO2Me-CH2CH2CH2cH2cH2-4-C1 5-Br C02Me-CH2CH2CB2cH2cH2-4-Br 5-Br CO2Me-CH2CN2CH2CH2CH2-.t 2 5 4 OCF3 5-BrCO2Me -CH2CH2CH2c~2cH2-4-CF3 4-F CO2Me-CH2CH2CH2cH2cH2-4-C1 4-F CO2Me-CH2CH2CH2CH2CH2-4-Br 4-F CO2MeCH2CH2CH2C~32cH2-4-OCF3 4-F CO2Me-CH2CH2CH2CH2CN2_ CF3 S-CF3 CO2Me -CH2CH2CN2cH2cH2-4-CF3 5-F CO2Me-CH2CH2CH2cH2cH2 ,~ 4-CF3 5-Cl Ph-CH2CH2CH2CH2~H2 4 CF3 S-Cl -CI-Ph -CH2CH2CH2CH2CH2-4-CF3 5-Cl C02Et -CH2CH2CH2cH2cH2-3 5 4-CF3 H C02Me-CH2CH20CH2cH2-4-Cl H C02Me-CN2CHZOcH2cH2-.
4-~r H C02Me-CN2CH20C~2cN2-.
, ' `' Z;l~f~0130 :
~1 R2 B R8 R12- ---4-OCF3 H CO2Me -CH2CH2~CH2CH2-q C~3 5-Cl CO2Me -CH2CH2OCH2CH2-4-C1 5-Cl CO2Me -CH2CH2OCH2CH2_ 4-Br 5-Cl CO2Me -CH2cH2OcH2cH2 4-OCF3 5-Cl CO2Me -CH2cH2OcH2cH2-4-CF3 5-Br CO2Me -CH2CH2~CH2cH2-4-C1 5-Br CO2Me -CH2cH2OcH2cH2 4-Br 5-Br CO2Me _CH2cH2OcH2cH2 4-OCF3 5-Br CO2Me -CH2cH2OcH2cH2 4-CF3 4-F CO2Me -CH2cH2OcH2cH2-4-C1 4-F CO2Me -CH2CH2OCH2CH2-4-Br 4-F CO2Me -CH2cH2OcH2cH2-4-OCF3 4-F CO2Me -CH2CH2OCH2CHz-4-CF3 5-CF3 CO2Me -CH2cH2OcH2cH2-`; 20 4-CF3 5-F CO2Me -CH2CH2OCH2CH2_ 4-CF3 5-Cl Ph -CH2cH2OcH2cH2 ~:. 4-CF3 5-C1 4-Cl-Ph -CH2CH2OCH2CH2-4-CF3 5-Cl CO2Et -CHzCH2OCH2CH2_ ;
~.i q-CF3 H CO2Me -CH2CHMeOCHMeCH2-:` 25 4-Cl H CO2Me -CH2CHMeOCHMeCN2-. 4-~3r H CO2Me -CH2CHMeOCHMeCH2-.. 4-OCF3 H CO2Me -CH2CHMeOCHMeCH2- ~ -~: 4-C~3 S-C~ C~2Me -CH2CHMeOCNMeCH2-.~ 4-C1 5-CI CO2Me -C~2CNMeOCHMeCH2_ :~ 30 4-Br 5-Cl CO2Me -CN2CHMeOCHMeCH2-~ 4-OCF3 5-Cl CO2Me -CH2CKMeOCHMeCH2_ .~ 4-CF3 5-Br C02Me -CH2CHMeOCHMeCH2-q-Cl 5-Br CO2Me -CN2CHMeOCNMeCN2_ 4-Br 5-Br C02Me -CH2C~MeOCHMeCH2-4-OCF3 5-Br CO2Me -CH2CHMeOCHMeCH2_ ~ ç-cr3 4-r C~2M~ -CNzCNMeOCNMoCNz-.. .. .
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4-C1 4-F C02~e -CH2CHMe~CHMeCH2-4-~r 4-F CO2Me -CH2C~M~OCHMeCH2_ 4-OCF3 4-F C02Me -CH2CHMeOCHMeCH2-~-CF3 5-CF3 C02Me -CH2CHMeOC~MeCH2-4 CF3 5-F CO2Me -CH2CHMeOCHMeCH2- !`
4-CF3 5-Cl Ph -C~2CHMeOCHMeCH2 4-CF3 5-Cl 4-CI-Ph -CH2C~MeOCHMeCH2-4-CF3 5-Cl CO2~t -CH2CHMeOCHMeCH2-4-CF3 H CO2Me Et cyClo-c6Hll 4-CI H CO2Me Et cyclo-C6Hli -Br H CO2Me Et cyclo-c6 4-OCF3 H CO2Me Et cyclo-C6H
4-C~3 5-Cl CO2Me Et cyclo-C
4-C1 5-Cl CO2Me Et CYC1~
^, 20 4-9r 5-Cl CD2Me Et cyclo-~6 ;`' 4-OCF3 5-Cl CO2Me Et CYC1-4-CF3 5-Br CO2Me Et cyclo-C
4-Cl S-Br CO2Me Et cyclo-C
4-Br 5-Br CO2Me Et cyclo-C6B
4-OCF3 5-9r CO2Me Et cyclo-c6Hll ~, 4-CF3 4-F CO2Me Et cyclo-C6Hll :
-~ 4-C1 4-~ CO2Me Et cyclo-C6H
;~ 4-Br 4-F CO2Me Et CYC1~
~-OCr3 4-F CO2Me Et cyclo-C6H
4-CF3 5-CF3 CO2Me Et cyclo-C6H
4-CF3 5~~ CO2Me Et cyCl~-c6H
~ 4-CF3 S-Cl Ph Et cyclo-C6H
:: 4-CF3 5-C1 4-Cl-Ph Et ~YCl~c6Hll. ' ~- 4-CF3 5-Cl CO2Et Et CYel~C6Nll ~ .
4-CF3 H CO2Me iPr CH2CH2CO2Et 4-Cl H CO2Me iPr CN2CH2C02Et "
4-Br H CO2Me iPr CH2CH2C2~t . . ~'-,.
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- . Rl R2B ~8 R12 4-OCF3 HCO2Me iPr CN2CH2C2Et : ~-C~3 S-Cl CO2Me ~Pr C~2CH2C2Et 4-C1 5-Cl CO2Me iPr CH2CH2~2Et 4-~r 5-Cl CO2Me lPr CH2CH2C2~t 4-OCF3 5-Cl CO2Me iP~ . CH2CH2C2Et 4-CF3 5-Br CO2Me iPr CH2 Q2C2Et ;~ 4-C1 5-Br CO2Me ~Pr CH2CH2C2Et 4-~r S-Br CO2Me iPr Q2CH2CO2Et 4-OCF3 5-Br CO2Me iPr CH2CH2CO2Et ~: 15 4-CF3 4-FCO2Me iPr Q2CH2CO2Et 4-C1 4-FCO2Me iPr CH2CH2C02Et 4-Br q-FCO2Me iPr CH2CH2C2Et ; 4-OCF3 4-FCO2Me iPr Q2CH2CO2Et 4-CF3 5-CF3 CO2Me iPr CH2CH2C2Et q-CF3 S-~CO2Me iPr CH2C~2C2Et .;~ 4-CE3 5-Cl Ph iPr CH2CH2C2Et .~ 4-CF3 S-Cl 4-Cl-Ph iPr CH2CH2C2Et 4-CF3 S-Cl CO2Et iPr C~2C~2C2Et .~ :
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S-SRlo Rl R2 Rlo . _ 4-CF3 H CO2Me tBu 4-Cl H CO2Me t8u .
4-Br H CO2Me tBu ~ ' ` 25 4-OCF3 H CO2Me tBu ~ .
; 4-CF3 S-Cl CO2Me tBu 4-C1 5-CI CO2Me tBu 4-8r S-CI CO2Me tBu 4-OCF3 5-Cl CO2Me tBu 4-CF3 5-Br CO2Me tBu 4-C1 5-8r CO2Me tBu 4-Br 5-Br CO2Me tBu 4-OCF3 S-~r CO2Me tBu -~ 4-CF3 4-F CO2Me tBu CO2Me tBu ' , , ' .
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~1 Rl R2 B Rlo 4-Br 4-F CO2Me tBu 4-OCF34-F CO2Me tBu 4-CF35-CF3 CO2Me tBu 4-CF35-F CO2Me ti3u 4-CF35-Cl Ph tBu 4-CF35-C14-Cl-Ph tBu 4-CF35-Cl c02Et tBu 4-CF3 H C~2Me Ph 4-Cl H CO2Me Ph 4-Br H CO2Me Ph 4-OCF3 H C02Me Ph 4-CF35-Cl CO2Me Ph 4-Cl S-Cl CO2Me Ph 4-Br S-Cl CO2Me Ph 4-OCF35-Cl CO2Me Ph 4-CF35-Br CO2Me Ph 4-Cl S-Br CO2Me Ph 4-Br S-Br CO2Me Ph 4-OCF35-Br CO2Me Ph 4-CF34-F CO2Me Ph 4-C14-F CO2Me Ph 4-F CO2Me Ph 4-OCF34-F C02Me Ph 4-CF35-CF3 C~2Me Ph n 4 CF35-F CO2Me Ph 4-CF35-Cl Ph Ph 4-CF35-C14-Cl-Ph Ph 4-CF3 S-Cl C02Et Ph ~:
4-CF3 H C02Me 4-Cl-Ph 4-CI H CO2Me 4-Cl-Ph 4-Br H CO2Me 4-Cl-Ph :
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2~3~?~30 Rl R2 Rlo . 4-OCF3 H CO2Me 4-Cl-Ph -CF3 5-Cl CO2Me 4-Cl-Ph 4-C1 5-Cl CO2Me 4 -Cl -Ph 4-8r 5-Cl CO2Me 4-Cl-Ph 4-OCF3 5-Cl CO2Me 4-Cl-Ph 4-CF3 5-8r CO2Me 4-Cl-Ph 4-C1 5-Br CO2Me 4-Cl-Ph .~
4-Br 5-8r CO2Me 4-Cl-Ph 4-OCF3 S-Br CO2Me 4-Cl-Ph 4 CF3 4 F C2Me 4-Cl-Ph 4-C1 4-F CO2Me 4-Cl-Ph .. 4-Br 4-F CO2Me 4-Cl-Ph 4-OCF3 4-F CO2Me 4-Cl-Ph Ç-CF3 5-CF3 CO2Me 4-Cl-Ph 4-CF3 5-F CO2Me 4-Cl-Ph ''~. - ,' .i, :~, .
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4-CF3 5-Br H O Me OEt 4-C1 5-Br H O Me OEt i 4-Br 5-Br H O Me OEt 4-OCF3 5-Br H O Me OEt ~, ~-CF3 5-Cl H O Me OEt .,. 4-C1 5-Cl H O Me OEt :~ 4-Br 5-Cl H O Me OEt ~= 4-CF3 S-C~3 H O Me OEt 4-CF3 4-F H O Me OEt 4-CF3 H H O Me OEt ; 4-CF3 S-Br CO2Me O Me OEt 4-CF3 5-Cl CO2Me O Me OEt 4 CF3 S-CF3 CO2Me O Me OEt ; 35 4 C~3 4-F CO2Me Me OEt .
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Z~f~0130 Rl R2 B V R~ ~9 . _ 4-CF3 H CO2Me Me OEt 4-CF35-Cl H S ~e OEt 4-C15-CI B S Me OEt 4-~r 5-CI H S Me OEt 4-CF35-Br H S Me OEt 4-CF35-F H S Me OEt 4-CF34-Cl H S Me OEt 4-CF34-F H S Me OEt 4-CF3 H N S ~e OEt , 15 4-CF35-Cl CO2Me S Me OEt - 4-CF35-Br CO2Me S Me OEt :` 4-CF35-F CO2Me S Me OEt 4-CF34-Cl CO2Me S Me OEt 4-CF34-F CO2Me S Me OEt 4-CF3 H CO2Me S Me OEt 4-CF35-Br B , O Me O-D-Bu 4-C15-Br H O Me O-n-Bu 4-Br 5-Br H O Me O-n-Bu ~; 4-OCF35-Br H O Me O-D-Bu . 25 4-CF35-Cl H O Me O-n-Bu 4-C15-Cl H O Me O-~-Bu i,~ 4-Br 5-Cl H O Me O-D-Bu -, 4-CF35-CF3 H o Me O-~-Bu . 4-CF34-F N O Me O-n-Bu 4-CF3 H B O Me O-n-Bu 4-CF35-Br CO2Ne o Me O-D-Bu .. 4-CF35-Cl CO2Me O Me O-n-Bu : 4-CF35-CF3 CO2Me O Me O-n-Bu 4-CF34-F CO2Me Me O-D-BU
' 35 4-Cr3 ~ CO2Me Me O-D-Bu h, 4-CF35-Cl H S Me O-D-Bu 4-C15-Cl N S Me O-n-Bu ." ~.'.
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~5 5. R2 B V 89 _ 4-Br 5-Cl H S Me O-n-8u 4-CF35-Br H S Me O-D-Bu 4-CF3 s-r H S .Me O-n-Bu 4-CF34-Cl H S Me O-n-Bu 4 CF34-F H S Me O-n-Bu 4-CF3 H H S Me O-D-Bu 4-CF35-Cl CO2Me S Me O-n-9u 4-CF35-Br CO2Me S Me O-n-13u - 4-CF35-F CO2Me S Me O-n-Bu 4-CF34-Cl CO2Me S Me O-n-Bu 4-CF34-F CO2Me S Me O n-Bu 4-CF3 H CO2Me S Me O-n-Bu 4-CF35-Br H O Me O-n-he~yl 4-C15-Br H O Me O-D-he~yl .~,, 4-Br 5-Br H O Me O-n-hexyl 4-OCF35-Br H O Me O-n-hexyl 4-CF35-Cl H O Me O-n-hexyl 4-C15-Cl H O Me O-n-hexyl 4-Br 5-Cl H O Me O-n-hexyl 4-CF35-CF3 H o Me O-n-he~yl :
-~ 4-CF34-F H O Me O-n-hexyl 4-CF3 H H O Me O-n-hexyl . 4-CF35-Br CO2Me O Me O-n-hexyl ; 4-CF3 s-Cl CO2Me O ~e O-n-hexyl 4-CF35-CF3 CO2Me O Me O-n-hexyl 4-CF34-F CO2Me Me O-D-hexyl 4-CF3 H CO2Me O Me O-n-he~yl 4-CF35-Cl H S Me O-n-hexyl 4-C15-Cl H S Me O-n-hexyl 4-Hr 5-Cl H S Me O-D-hexyl 4-CF35-Br H S Me O-D-hexyl 4-CF35-F H S Me O-n-he~yl . :
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Z~ ?~1;30 e6 4-CF34-Cl H S Me O-n-he~yl 4-CF34-F H S Me O-n-he~yl 4-CF3 ~ ~ S Me O-n-he~yl 4-CF35-Cl CO2~e S ~e O-D_~Y1 4-CF35-Br CO2Me S Me O-n-he~yl - 4-CF35-F ~02Me S Me O-n-hexyl 4-CF34-Cl CO2Me S Me O~-he~yl 4-CF3 ~-~ CO2Me S Me O-n-he~yl ; 4-CF3 H CO2Me S Me O-n-he~yl 15 4-CF35-Br H O Me O-n-octyl ' 4-C15-Br H O Me O-n-octyl 4-~r 5-Br H O Me O-n-octyl 4-OCF35-Br H O Me O-n-octyl 4-CF35-Cl H O Me O-n-octyl 4-C15-Cl H O Me O-n-octyl 4-Br S-Cl H O Me O-n-octyl ~: 4-CF35-CF3 ~ O Me O-n-octyl . 4-CF34-F H O Me O-n-octyl 4-CF3 H H O Me O-n-octyl 4-CF35-~r CO2Me O Me O-n-octyl 4-CF35-Cl CO2Me O Me O-n-octyl 4-CF35-CF3 CO2Me O Me O-n-octyl 4-CF34-F CO2Me Me O-n-octyl 4-CF3 H CO2Me Me O-n-octyl 4-CF35-Cl H S Me O-D-o~tyl 4-C15-Cl N ~ Me O-n-o.ctyl 4-~r 5-Cl H S Me O-n-octyl 9-CF35-Br H S Me O-n-octyl : ~-CF35-F H S Me D-D-octyl 4-CF34-Cl N S Me O-n-octyl 4-CF3 ~-F H S Me O-n-octyl 4-CF3 H HS Me O-n-octyl . , ' ~
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2t~01.~0 ~7 Rl R2 ~ V RB R9 _ 4-CF35-Cl CO2Me ~ Me O-D_OCtY1 4-CF35-~r CO2Me S Me O-D_~CtY1 4-CF35-F C2~e 5 Me O-n-octyl : 4-CF34-Cl CO2Me S Me O-D_OCeY1 4-CF34-F CO2Me S Me O-n-~ctyl 4-CF3 H CO2Me S Me O-n-octyl 4-CF35-Br H O He O-n-decyl . 4-C~ 5-Br H O Me O-n-decyl 4-Br 5-~r B O Me O-n-decyl 4-OCF35-Br H O Me O-n-decyl 4-CF35-Cl H O Me O-D-deCyl 9-C15-Cl H O Me O-n-decyl 4-Br S-Cl H O Me O-n-decyl ~ 4-C~35-CF3 H O Me O-n-decyl .~ 20 4-CF34-F H O Me O-n-decyl - 4-CF3 N H O Me O-n-decyl 4-CF35-ar CO2Me O Me O-n-decyl : 4-CF35-Cl CO2Me O Me O-n-decyl ~` 4-CF35-CF3 Co2Me o Me O-n-decyl :- 25 4-CF34-F CO2Me O Me O-n-decyl 4-CF3 H CO2Me Me O-n-decyl . 4-CF35-Cl H S Me O-n-decyl - 4-Cl S-Cl H S Me O-n-decyl 4-Fr 5-Cl H S Me O-n-decyl 3 S Me O-~-dccyl 4-CF35-F H S Me O-D-decyl ~-~ 4-CF34-Cl H S Me O-D-decyl 4-CF34-F H S Me O-n-decyl 4-CF3 H H ~ Me O-D-deCyl 4-C~35-cl CO2Me S Me O-D-decyl . 4-CF35-Br CO2Me S Me O-n-decyl 4-CF35-F CO2Me S Me O-~-decyl 4-CF34-Cl CO2Me S Me O-n-decyl ., :
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4-CF3 5-Cl H S Me O-cec-Bu q-Cl 5-Cl H S Me O-cec-Bu . 4-Br 5-Cl H S Me O-~ec-Bu .. . .
4-CF3 S-Br H S Me O-cec-Bu '. 4-CF3 5-F H S Me O-cec-Bu 4-CF3 4-Cl N S Me O-~ec-Bu 4-CF3 4-F H S Me O-cec-Ku 4-CF3 H H S Me O-cec-8u 4-CF3 5-Cl C02Me S Me O-cec-Bu 4-CF3 5-Br C02Me S ~e O-sec-Bu 4-CF3 s-r C02Me S Me O-sec-Bu 4-CF3 d-Cl C02Me S Me O-cec-9u 4-CF3 4-F C02Me S Me O-cec-Bu ~-CF3 N C2M~ 5 lle O-~-c-Bu ;~''"
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4-C1 5-Cl H S Me NMe2 4-Br 5-Cl ~ S Me NMe2 ., 4-CF3 5-Br H S Me NMe2 ,: 4-CF3 5-F H S Me NMe2 . 25 4-CF3 4-Cl B S Ne NMe2 ::~ 4-CF3 4-F H S Me NMe2 4-CF3 H H S Me NMe2 4-CF3 5-Cl CO2Me S Me NMe2 4-CF3 5-Br C~2Me S Me NMe2 : 4-CF3 5-F C02Me S Me NMe2 -~
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4 CF35-F H S iPr OEt 4-CF34-CI H S iPr OEt 4-CF34-F H S iPr OEt 4-CF3 H H S iPr OEt 4-CF35-Cl CO2Me S iPr OEt 3D 4-CF35-Br CO2Me S iPr OEt : 4-CF35-F CO2Me S iPr OEt ~: 4-CF34-Cl CO2Me S iPr OEt .. 4-CF34-F CO2Me S iPr OEt 4-CF3 H CO2Me S iPr OEt : 35 ' ' .`''' .
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4-CF3 5-Cl CO2Me O CH2Ph NEt2 4-CF3 S-CF3 CO2Me O CH2Ph morpholino : 4-CF3 4-F CO2Me O CH2Ph 4-Cl-Ph 4-CF3 H CO2Me O CH2Ph Et 4-CF3 5-Cl H S CH2Ph Ph , .
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` 15 4-CF3 5-Br CO2Me S Me NEt2 g-CF3 s-F CO2Me S Me NEt2 4-CF3 4-Cl C02Me S Me NEt2 ~:
4-CF3 4-F CO2Me S Me NEt2 4-CF3 H CO2Me S Me NEt2 2 0 4-CF3 5-Br H 0 Me piperidino 4-C1 5-Br H O Me 6ec-Bu 4-Br 5-Br H O Me n-he%yl 4-OCF3 5-Elr H O Me Ph 4-CF3 5-Cl H O Me 4-Cl-Ph 2 5 4-C1 5-Cl H o Me 4-Me-Ph 4-Br 5-Cl H O Me n-Bu 4-CF3 5-CF3 H . O Et NMe2 4-CF3 4-F H O Et NEt2 - 4-CF3 H H O Et morpholino i` 3 0 4-CF3 5-Br CO2Me O Et iPr 4-CF3 5-Cl CO2Me O Et n-Bu 4-CF3 5-CF3 CO2Me O Et Ph :.
4-CF3 4-F CO2Me O Et 4-MeO-Ph ; 4-CF3 H CO2Me Me NMe2 3 5 4-CF3 5-Cl H S Me NEt2 4-C1 5-Cl H S Me morphollno 4-Br 5-Cl H S Me iPr :, .. ..
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4-CF35-Br H S Me ~-8u 4-CF35-F H S Me Ph 4-CF3 ~-Cl H S Me 4-MeO-Ph 4-CF3 ~-F H S Et piperi~i~o ' 4-CF3 H H S Et 6ec-~u 4-CF35-Cl CO2Me S Et ~-hesyl 4-CF35-Br CO2Me S St Ph 4-CF35-F CO2Me S Et 4-Cl-Ph ~-C~34-cl C02Me S Et 4-Me-Ph lS 4-CF34-F CO2Me S Et n-Bu 4-CF3 H ~02Me S Et 2,6-di-Me-morpholino ` 4-CF35-Br H O iPr NMe2 : 4-C15-Br H O iPr NMe2 4-Br S-Br H O iPr NMe2 4-OCF35-Br H O iPr NMe2 ` 4-CF35-Cl H O iPr NMe2 :
~`. 4-C15-Cl H O iPr NMe2 4-Br S-Cl H O iPr NMe2 4-CF35-CF3 H o iPr NMe2 .. 2~ 4-CF34-F H O iPr NMe2 4-CF3 H H O iPr NMe2 4-CF35-Br CO2Me O iPr NMe2 4-CF35-Cl CO2Me O iPr NMe2 4-CF35-CF3 CO2Me o iPr NMe2 .~ 30 4-CF34-F C02Me o lPr NMe2 4-CF3 H C02Me iPr NMe2 -~ 4-CF35-Cl N S {Pr NM
4-C15-Cl H S ~Pr NMe2 : 4-Br 5-Cl H S ~Pr NMe2 4~CF35-Br H S iPr NMe2 4-CF35-F H S iPr NMe2 .~ .
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Z1~ 30 1 2 B V RB Etg 4-CF3 4-Cl H S ~Pr NNe2 4-CF3 4-F H S {Pr NMe2 4-C~3 H H S lPr NMe2 4-CF3 5-Cl C02Me S iPr NMe2 4-CF3 5-Br CO2Me S {Pr NMe2 4-CF3 5-F CO2Me S ~Pr NMe2 4-CF3 4-Cl CO2Me S lPr NMe2 4-CFB 4-F CO2Me S 1Pr NMe2 4-CF3 H CO2Me S lPr NMe2 . . .
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4-CF3 5-Br H O tBu S OEt OEt 4-C1 5-9r H O tBu S OEt OEt . 4-Br 5-Br H O tBu S OEt OEt 4-OCF3 5-Br H O tBu S OEt OEt .
.~ 4-CF3 5-Cl H O t8u S OEt OEt ; 4-C1 5-Cl H O tBu S OEt OEt 9-Br 5-Cl H O tBu S OEt OEt j 4 CF3 5 CF3 N o tBu S OEt OEt `~ 30 4-CF3 4-F ~ O tBu S OEt OEt : 4-CF3 H H O tBu S OEt OEt 4-CF3 S-Br CO2Me O tBu S OEt OEt 4-CF~ S-Cl CO2Me O tBu ~ OEt OEt 4-CF3 5-CF3 C02Me O tBu S OEt OEt :
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Rl Rz B V RB Y y Rlo Y Rll 4-CF3 4-F CO2Me tBu S OEt OEt 4-CF3 H CO2Me t8u ~ OEt OBt 4-CF3 5-C~ H S tBu S OEt OEt 4-C1 5-Cl H S tBu S OEt OEt 4-8r S-Cl H S tBu ~ OEt OEt 4-CF3 S-Br ~ S t8u S OEt OSt 4-CF3 5-F fi S tBu S ~Et OEt 4-CF3 4-Cl ~ S tBu S OEt OEt 4-CF3 4-F H S tBu S OEt OEt .`
4-CF3 H H S t8u S OEt OEt .
:. 4-CF3 S-Cl CO2Me S thu S OEt OEt , 4-CF3 5-Br CO2Me S tRu S OEt OEt :; 4-CF3 5-F CO2Me S tBu S OEt OEt ..
4-CF3 4-Cl CO2Me S t8u S OEt OEt ':
; 20 4-CF3 4-F CO2Me S tBu S OEt OEt 4-CF3 H CO2Me S tBu S OEt OEt 4-CF3 5-Br H O tBu S -OCH2C(Me)2CH20-4-C1 5-Br H O t8u S -OCH2C(Me)2CH20-4-8r 5-Br H O tBu S -OCH2C(Me)2CH20-~. 25 4-OCF3 5-Br H O tBu S -OCH2C(Me)2CH20- ~.
`~X 4-CF3 5-Cl H O teu S -OCH2C(~e)2CH20-4-C1 5-Cl H O tBu S -OCH2C(Me)2CH20-4-Br 5-Cl H O t8u S -OCH2C(Me)2CHzO-4-CF3 5-CF3 H tBu S -OCH2C(M~)2CH20-4-CF3 4-F H O tBu S -OCH2C(Me)2CH2 . 4-CF3 H H O tBu S -OCH2C~Me)2C~20- -~
4-CF3 5-Br CO2Me O tBu S -OCH2G(Me)2CH20_ 4-CF3 5-Cl CO2Me O tBu S -OCH2C(Me~2CH20_ ; 4-CF3 5-CF3 CO2Me O tBu S -OCH2C(Me)2CH20-~`:' 35 4-CF3 4-F CO2Me O tBu S -OCH2C(Me)2CH20-4-CF3 H CO2Me t8u S -OCH2C(Me)2CH20-4 CF3 5-Cl H S t8u S ,OCH2c(Me)2Q20-"
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4-C1 5-Cl H S tBu ~ -OCH2C(Me)2CH2O-4-9r 5-Cl H S tBu S -OCH2C(Me)2CH2O-4-CF3 5-Br N S tBu S -OCH2C(Me)2CH20-4-CF3 5-F H S tBu S -OCH2C(Me)2CH2O-:: 10 4-CF3 4-Cl H S tBu S -OCH2C(Me)2CH2O-4-CF3 4-F H S tBu S -OCH2C(Me)2C~2 4-CF3 ~ H S t~u S -OCH2C(Me)2CH20-4-CF3 5-C~ CO ~ S t~u S -OCH2C(Me)2CH20-4-CF3 5-Bs CO2Me S tBu S -OCH2C(Me)2cH2 4-CF3 5-F CO2Me S tBu S OCH2C(Me)2c~2O-4-CF3 4-Cl CO2Me S tBu S -OCH2C(Me)2CH2O- ::
4-CF3 4-F CO2Me S tBu S -OCH2C(Ne)zCH2O-4-CF3 H CO2Me S tBu 6 -OCH2C(Me)2CH2O
~ 4-CF3 5-Br H O tBu S OCH2CH2CH2O-:. 4-C1 5-Br H O tBu S -OCN2CH2CH2O-4-Br S-Br H O tBu S -OCH2CH2CH2O-4-OCF3 5-2r H O tBu S OCH2CH2CH2O_ 4-CF3 5-Cl H O tBu S CH2cH2cH2-4-Cl S-CI H O tBu S -OCH2CH2CH2O-4-Br 5-Cl H O t~u S CH2CH2CH2O-4-CF3 5-CF3 H O tBu S -OCH2CH2CH2O-4-C~3 4-F H O tBu S -OCH2CH2CH2O_ 4-CF3 H H O tBu S -CH2cH2c~2-4-CF3 5-Br CO2Me O tBu S -OCH2CH2CH2O-`~ 30 4-CF3 5-Cl CO2Me O tBu S -OCB2CH2CH2O-4-CF3 5-CF3 CO2Me O tBu S -OCH2CH2CH2O-: 4-CF3 4-F CO2Me t~u S -CH2cH2~H2-~; ~-CF3 H CO2Me O tBu S -OCH2CH2CH2O-4-CB3 S-Cl H S tBu S -CH2cH2~H2-4-Cl S-Cl H S tBu S -OCH2CH2CH2O-4-Br S-Cl H S tBu S -OCH2CH2CH2O_ , .:. :
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; 4-CF3 4-Cl ~ S tBu S -OCH2CH2CH20-; 4-CF3 4-F H S t~u S -OCH2C82CH20-4-CF3 N H S tBu S -CH2cH2cH2-4-CF3 5-Cl CO2Me S tBu S -~CH2CH2CH20- .
4-CF3 5-Br CO2Me S tBu S -OCH2CH2CH20- :
. 4-CF3 S-F CO2Me S tBu S -OCH2CH2CH20-4-CF3 9-Cl CO2Me S tBu S -OCH2CH2CH20-4-CF3 4-F CO2Me S tBu S -OCH2CH2CH20-. 4-CF3 H CO2Me S tBu S -OCH2CH2CH20-4-CF3 5-Br H O tBu S -OCH2CH20-. 4-Cl S-Br H O tBu S -OCH2CH20-``~ 4-Br S-Br H O tBu S -OCH2CH20- :
4-OCF3 5-Br H O t~u S -OCH2CH20- : .
; 4-CF3 S-Cl H O tBu S -OCH2CH20-4-C1 5-Cl N O tBu S OCH2CH20-4-Br 5-Cl H O tl3u S -OCH2CH20- ~,:
4-CF3 S-CF3 H O t8u S OCH2CH20-: 25 4-CF3 4-F H O tBu S -OCH2CH20-~ 4-CF3 H H O tBu S -CH2cH2-.,' 4-CF3 S-Br CO2Ne O tBu S -OCH2cH2 4-CF3 S-Cl CO2Me O tBu S OCH2CH20-4-CF3 S-CF3 CO2Me O tBu S -OCH2CH20-- 30 4-CF3 4-F CO2Me tBu S -OCH2CH20-s~ 4-CF3 H C02Me tBu S -OCH2CH20-4-CF3 5-Cl H S t8u S -OCH2CH20-``` 4-Cl S-Cl H S tBu S -OCH2CH20-4-Br 5-Cl H S tBu S -OCH2CH20-~, 35 4-CF3 S-Br H S tBu S -OCH2CH20- :~
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4-CF3 5-Er CO2Mr O iPr S OEt OEt 4-CF3 S-Cl CO2Me O iPr S OEt OEt . 4-CF3 5-CF3 CO2Me O iPr S OEt OEt 4-CF3 4-F CO2He iPr S OEt OEt 4-CF3 H CO2Me O iPr S OEt OEt 4-CF3 5-Cl H, S iPr S OEt OEt 4-C1 5-Cl H S ~Pr S OEt OEt 4-Br 5-Cl H S ~Pr S OEt OEt 4-CF3 5-~r H S iPr S OEt OEt 4-CF3 5-E H S iPr S 3Et OEt -. 4-CF3 4-Cl H S iPr S OEt OEt 4-CF3 4-F N S iPr S OEt OEt 4-CF3 H H S iPr S OEt OEt . 4-CF3 5-Cl CO2Me S iPr S OEt OEt '. ;' ::
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4-CF3 ~-Cl C02Me S iPr S -OCHiC(Me)2CH20-4 CF3 4 F CO2Me S lPr S -OCH2C(Me)2CN20-4-CF3 8 CO2Me S iPr E -OCH2C(Me)2CH20-4-CF3 5-Br ~ O Me ~ OEt OEt 10 4-C1 5-Br H O Me S OEt OEt 4-Br S-Br H O Me S OEt OEt 4-OCF3 5-Br H O Me S OEt OEt 4-CF3 5-Cl H O Me S OEt OEt 4-C1 5-Cl ~ O Me S OEt OEt 15 4-Fr 5-Cl H O Me S OEt OEt 4-CF3 5-CF3 H O Me S OEt OEt 4-CF3 4-F H O Me S OEt OEt ~:~ 4-CF3 H H O Me S OEt OEt 4-CF3 S-Br CO2Me O Me S OEt OEt 4-CF3 S-Cl CO2Me O Me S OEt OEt 4-CF3 5-CF3 C02Me O Me S OEt OEt 4-CF3 4-F CO2Me Me S OEt OEt 4-CF3 H CO2Me Me S OEt OEt ~- 4-CF3 S-Cl H S Me S OEt OEt .` 25 4-Cl S-Cl H S Me S OEt OEt 4-Br S-Cl N S Me S OEt O~t 4-CF3 S-Br N S Me S OEt OEt ~.
4-CF3 S-F H S Me S OEt OEt ~; 4-CF3 4-Cl H S Me S OEt OEt 30 4-CF~ 4-F H S Me S OEt OEt 4-CF3 H H S Me S OEt OEt ::
i 4-CF3 S-Cl CO2Me S Me S OEt OEt . 4-CF3 S-~r CO2Me S Me S OEt OEt ; 4-CF3 5-F C02Me S Me S OEt OEt .. - 35 4-CF~ 4-Cl C02Me S Me S OEt OEt : 4-CF3 4-F CO2Me S Me S OEt OEt -~ 4-CF3 H CO2Me S Me S OEt OEt - .-' :. , ' ' . '.. : ,,: ,:,: .. .. ::. .: . .: . . :.: , . ::
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4-Br 5-Cl ~ O tBu O OEt OEt - 4-CF35-CF3 B O tBu O OEt aEt 4-CF34-F H O tnu O OEt OEt 4-CF3 H H O t8u O OEt OEt ,. 4-CF35-Br COzMe O t8u O OEt OEt 4-CF35-Cl CO2Me O tBu O OEt OEt 4-CF35-CF3 CO2Me O t9u O OEt OEt - 4-CF34-F CO2Me t8u O OEt OEt 4-CF3 H CO2Me t8u O OEt OEt 4-CF35-CI H , S t8u O OEt OEt ,.'. 4-C15-Cl H S tBu O OEt OEt :.Y- 4-9r 5-Cl H S t8u O OEt OEt . 4-CF35-8r H S tBu O OEt OEt 4-CF35-F H S tBu O OEt OEt 4-CF34-Cl H S tBu O OEt OEt 4-CF3 q-F H S tBu O OEt OEt ;~ 9-CF3 H ~ S tBu O OEt OEt `~' 4-CF35-Cl CO2Me S tBu O OEt OEt , 30 4-CF35-Bs CO2Me S tBu O OEt OEt 3 4-CF35-F CO2Me S tBu O OEt OEt ~ 4-CF34-Cl CO2Me S t8u O O~t OE~ :-.. 4-CF34-F CO2Me S tBu O OEt OEt : 4-CF3 H CO2Me S tBu O OEt OEt :' .`' . ' , .
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104-CF35-Cl H O t8u O -OCH2ClMe)2CH2O-4-C15-Cl H O tHu O -OC~2C(Me)2CH2O-4-Br 5-Cl H O tBu O -OCH2C(Me)2CH2O-4 CF35-CF3 H ~ t8u O -OCH2C(Me)2CH2O-4-CF34-F H O tBu O -OCH2C(Me)2CB2O-154-CF3 ~ H O t8u O -OCH2C(Me)2CH2O-4-CF3 5-Br CO2Me O tBu O -OCH2C(Me)2C~2O-4-CF3 5-Cl CO2Me O tBu O -OCH2C(Me)2CH2O-4-CF3 5-CF3 CO2Me O tBu O -OCH2C(Me)2CH2O-4-C}3 4-F CO2Me O t8u o -OCH2C(Me)2CH2O-4-CF3 N CO2Me t8u O -OCH2C(Me)2CH2O-4-CF35-Cl H S tBu O -OCH2C(Me12CH2O-4-C15-Cl N S tBu O -OCH2C(Me)2CH2O-- 4-8r 5-Cl H S t8u O -OCH2C(Me)2CH2O-4-CF35-Br H S t8u O -OCH2C(Me)2CH20-254 CF35-F H S t8u o -OCH2C(Me)2CN2O--CF34-Cl H S t5u O -OCH2C(Me)2CH2O-. 4-CF34-F H S t8u O -OCH2C(Me)2CH2O- :~
4-CF3 H N S tBu O -OCH2C(Me)2CH2O-4-CF35-C~ C~2Me S tBu O -OCH2C(Me)2CH20-4-CF35-Fr CO2Me S tBu O -ocHzc(Me) 4-CF35-F CO2Me S tBu o -OCH2C(Me)2CH2O-4-CF34-C~ C02Me S t~u O -OCH2C(Me)2CH20-4-CF3 q-F C02Me S tBu O -OCH2C(Me)2CH20-4-CF3 N CO2Me S tBu O -OCH2C(Me)2CH2O-: 35 . "
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4-CF35-Br CO2Me S iPr O Et OEt 4-CF35-F CO2Me S iPr O Et OEt : 20 4-CF34-Cl CO2Me S iPr .O Et OEt 4-CF34-F CO2Me S iPr O Et OEt 4-CF3 H CO2Me S iPr O Et OEt 4-CF35-Br N O iPr O Et O-iPr ; .
4-C15-Br H O iPr O Et O-iPr , 25 4-Br 5-Br H O iPr O Et O-iPr 4-OCF35-Br H O iPr O Et O-iPr 4-CF35-Cl H O iPr O Et O-iPr '.~ 4-Cl S-Cl H O iPr O Et O-iPr 4-8r 5-Cl N O iPr O Et O-iPr 4-CF35-CF3 H O ~Pr O Et O-lPr 4-CF34-F H O iPr O Et O-iPr 4-CF3 H H O iPr O - Et O-iPr -:' 4-CF35-8r CO2Me iPr O Et O-~Pr ~-CF35-Cl CO2Me O lPr O Et O-lPr q-CF35-CF3 C2Me O ~Pr O Et O-iPr 4-CF34-F CO2Me O iPr O Et O-iPr ~ 4-CF3 H CO2Me iPr O Et O-iPr .~ .- .
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Rl R2 B V RB Y' Rlo Y Rll 4-CF3 5-Cl H S iPr O Et O-iPr 4-C1 5-Cl H ~; ~Pr O Et O-iPr 4-Br 5-Cl H ~i iPr O Et O-~Pr 4-CF3 S-Br H S iPr O Et O-iPr ~ CF3 5-F ~ S lPr O Et O-iPr 4-CF3 4-Cl H S iPr O Et O-iPr 4-CF3 4-F H S iPr O E:t O-iPr 4-CF3 H H S iPr O Et O-iPr 4-CF3 5-Cl CO2Me S iPr O Et O-iPr 4-CF3 S-13r C02Me S iPr O Et O-iPr 4-CF3 5-F CO2Me S iPr O Et O-iPr 4-CF3 4-Cl CO2Me S iPr O Et O-iPr :- 4-CF3 4-F CO2Me S iPr O Et O-iPr 4-CF3 B CO2Me S iPr Q Et O-iPr 2 0 4-CF3 5-Br H O iPr O Et OPh 4-C1 5-Br H O lPr O Et OPh ;; 4-9r 5-Br H O iPr O Et OPh 's 4-OCF3 5-Br H O iPr O Et OPh 4-CF3 5-Cl H O iPr O Et OPh 4-C1 5-Cl H O iPr O Et OPh ' 4-Br S-Cl H O iPr O Et OPh 4-C~3 5-CF3 H O iPr O Et OPh :~ 4-CF3 4-F H O iPr O Et OPh 4-CF3 N H O iPr O Et OPh 3 o 4-CF3 5-Br CO2Me iPr O Et OPh 4-CF3 5-Cl CO2Me O iPr O Et OPh 4-CE'3 5-CF3 C02Me O lPr O Et OPh 4-CF3 4-E C02Me O iPr O Et OPh 4-CE3 H CO2Me iPr O St OPh 3 5 4-~F3 5-Cl N S iPr O Et OPh 4-C1 5-Cl H S iPr O Et OPh ,, .
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Rl R2 B Y R8 YRlo Y Rll 4-Br . 5-Cl H S ~Pr O ISt OPh 4-CF3 5-8r H S lPr O ~t OPh ~-CF3 5-F H S iPr O Et OPh 4 CF3 4-Cl ~ S iPr O Et OPh 10~--CF3 4-r 9' S iPr O tt OPh 4-CF3 H H S lPr O Et OPh 4-CF3 5-Cl CO2Me S iPr O Et OPh ~-CF3 5-8r C2Me E; ~Pr O ~it OPh 4-CF3 5-F CO2Me S iPr O Et OPh 4-CF3 4-Cl C2M~ S iPr O E:t OPh 4-CF3 4-F CO2Me S iPr O Et OPh. !`
4-CF3 H ~02Me S iPr O Et OPh ;.~ 4-CF3 5-Br H 0 iPr O Ph OEt 4-C1 5-}lr H O iPr O Ph OEt : 2 o 4-E~r 5-EJr H O iPr O Ph OEt 4-OCF3 5-Br H O ~Pr O Ph OEt q-CF3 5-Cl H O iPr OPh OEt .~ 4-C1 5-Cl H O iPr OPh OEt .
4-Br 5-Cl H O iPr OPh OEt . 2 5 4-CF3 5-CF3 H o iPr OPh OEt 4-CF3 4-F H O iPr OPh OEt .~ 4-CF3 H H O iPr O Ph OEt 4 CF3 S-E~r C02Me O lPr O P2~ OEt 4-CF3 5-Cl CO2Me .O ~Pr O Ph OEt ~l-cF3 5_~ F3 C02Me O iPr O Ph OEt ~-CF3 ~-F C02Me lPr O Ph OE;t -~, 4-CF3 H CO2Me O iPr O Ph OEt 4-CF3 5-C~ a ~ iPr O Ph OEt 4-Cl S-Cl ~1 5 iPr O Ph O~:t : --.
`:~ 3 S 4-Br 5-Cl H S iPr O Ph OEt 4-CF3 5-Br H 5 iPr O Ph OEt ~ ~;.
4-CF3 5-F H S iPr O Ph OEt ~ ~;
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4-CF3 4-Cl H SiPr O Ph OEt 4-CF~ q-F H S ~Pr O PhOEt ~-CF3 1~ H S iPr O PhO.Et 4-CF3 5-Cl CO2Me S iPr O Ph OEt 4-CF3 5-Br C2M~ S iPrO Ph OEt 4-CF3 5-F CO2Me S ~PrO Ph OEt q-CF3 4-Cl CO2Me S ~PrO Ph OEt 4-CF3 4-F C02Me S iPrO P~ ~Et . 4-CF3 H C2Me S iPrO Ph OEt - 15 4-CF3 5-Br H O t8u O Et OEt 4-C1 5-8r H O t8u O EtOEt 4-8r 5-8r H O t8u O EtOEt 4-OCF3 5-Br H O tBu O EtOEt 4-CF3 5-Cl H O t8u O Et OEt 2 0 4-C1 5-Cl H O tBu O EtOEt . 4-8r 5-Cl H O t8u O EtOEt 4-CF3 5-CF3 H O tBu O Et OEt 4-CF3 4-F H O tBu O Et OEt 4-CF3 H H O t8u O Et OEt 2 5 4-C~3 5-8r CO2Me tBuO Et OEt : 4-CF3 5-Cl CO2Me tBuO Et OEt .. , 4-CF3 5-CF3 C~02Me ot8u O Et OEt 4-CF3 4-F CO2Me tBu O Et OEt q-CF3 8 CO~Me O tl3u O Et OEt n 4-CF3 S-Cl 8 5 tl~u O Et OEt .: 4-C1 5-Cl H S tBu O IStOEt -i 4-8r 5-Cl N S tBu O Et. OEt 4-CF3 5-Br 13 5t~u O Et OEt 4-CF3 5-F H S t8u O I:t OEt 3 5 4-CF3 4-C1 ~3 S tBuO Et OEt 4-CF3 4-F H S tBu O Et OEt . . .
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Z~00130 R2 B V 28 Y' RlC Y Rll 4-CF3 H H S tBu O Et, . OEt 4-CF3 5-Cl C02Me S tBu O Et OEt ~l-cF3 S-Br CO2Me S tBu O Çt OEt 4-CF3 5-F C02Me S tBu O Et OEt ~.
4-CF3 4-Cl CO2Me S tBu O Et OEt 4-CF3 4-F CO2Me S tBu O Et OEt 4-CF3 13 C02Me S tBu O Et OEt 4-C1 5-Br H O iPr S Et O-~Pr 4-Br 5-Br H O iPr S Et OPh 4-OC~3 5-Br H C> iPr S Ph OEt 4-CF3 5-Cl H O iPr S Ph O-iPr .~ 4-C1 5-Cl H O iPr S Ph OPh 4-Br S-Cl ~ O tBu S Et OEt '-' 4-CF3 5-CF3 H tBu S Et O-iPr 2 0 4-CF3 4-F H O tBu S Et OPh ; 4-CF3 H H O tBu S Ph OEt 4-CF3 5-i3r CO2Me tBu S Ph O-iPr ~,; 4-CF3 5-Cl CO2Me O tBu S Ph OPb -.~ 4-CF3 5-Br H S iPr S ~Pr OEt . 2 5 4-CF3 5-F H S iPr S iPr O-iPr ~- 4-CF3 4-Cl H S iPr S iPr OPh 4-CF3 4-F H S iPr S DPr OEt 4-CF3 H H S iPr S nPr O-iPr 4-CF3 5-Cl C2Me S iPr S nPr OPh ~ i 3 o 4-CF3 5-Br C02Me ~; tBu S Me OEt i~ ;
4-CF3 5-F C02~e S tBu S ~Se O-iPr ~ "
- e-CF3 4-Cl C02Me S tBu S Me OPh ~~
4-CF3 ~-F C02Me S ~Bu E; ~lle O-sec-8u '`
4-CF3 H CO2Me S tBu S Me O-nPr .
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, ,,, ' . ", 2~C~0130 T~ble 12 : 5 lC
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'. 4-CF3 5-8r H O Et Et 4-C1 5-Br H O Et Et 4-8r 5-Br H O Et Et . 4-OCF3 5-8r H O Et Et 4-CF3 S-Cl ~ Et Et 4-C1 5-Cl N O Et Et ; 4-Br 5-Cl H O Et Et 4-CF3 5-C~3 H o St Et 4-CF3 4-E H O Et Et 4-CF3 H H O Et Et ` 4-CF3 5-Br CO2Me O Et tt :' 4-CF3 5-CI CO2Me O ~t Et . . .
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; - ' , 2~00130 Rl R2 E~ V Rlo R
: 5 4-CF3 5-CF3 C~2Me O Et St ~-CF3 q-F C2M~ Et Et 4-CF3 H C2~e ~t Et - 4 CF3 S-Cl ~ S Et Et 4-C1 5-Ci H S Et Et 4-Br 5-Cl H S Et Et 4-CF3 5-9r H S Et Et 4-CF3 5-F H S Et Et 4-CF3 4-Cl H S Et St 15 4-CF3 4-F H S Et Et :-; 4-CF3 H H 5 Et Et '; 4-CF3 5-Cl C02Me S St Et 4-CF3 5-9r C02Me S Et Et 4-CF3 5-F C02Me S Et Et ., 20 4-CF3 4-Cl C02Me S Et. Et `~: 4-CF3 4-F C02Me S Et Et 4-CF3 H C02Me S Et St , ~5 .
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N-N ~ 1 .~ ~N `, ' 15 S-N-Re , R, 2 .
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:~ 20 :~.; Rl R2 B V RB R12 . .. i .
.~ 4-CF3 5-Br H O nBu DBu .; 4-C1 5-Br H O n9u DBu .. 25 4-Br 5-Br H O nBu ~Bu :. 4-OCF3 5-8r H O nBu nBu 4-CF3 5-Cl H O n8u DBu ~.~ 4-C1 5-Cl H O ~Bu nBu :.' 4-Br 5-Cl H O nBu nBu . 30 4-CF3 5-CF3 H O nBu ~Bu ,ri 4-CF3 4-F H O nBu D8U
.X 4-CF3 H ~ DBu DBu 4-CF3 5-8r CO2Me D8U n8u 4-CF3 5-Cl CO2Me O DBu nBu 4-CF3 5-CF3 CO2Me o D8U DBU
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2~C~0~310 .:.
. Rl R2 B V R,3 ~12 4-CF3 4-F C02Me nBu ~113U
. 4-CF3 B C02Me ~Bu n~3u 4-CF3 5-Cl H ~ nBu l~Bu 4-C1 5-Cl H S nl~u DBu ~-8r 5-Cl H S l~Bu ~Bu 4-CF3 5-Br H S nBu nBu 4-CF3 5-F ~ S nBu nBu 4-CF3 4-Cl ~1 5 ~Bu nl~ ~
4-CF3 4-F H S nBu nBu ~ ~ `
4-CF3 H H S nBu nBu ` 4-CF3 5-Cl CO2Me S nBu nBu . !
4-CF3 5-Br CO2Me S nBu nBu -~:
.~ 4-CF3 5-F CO2Me S rlBu ~Bu 4 CF3 4-Cl C02~e S nBu IlBu 2 0 4-CF3 4-F C02Me S nl~u nBu 4-CF3 H CO2Me 5 ~IBu nBu 4-CF3 5-Br H O -cH2c82cHzcH2cH2 4-C1 5-Br H O -CH2CH2CH2cH2cH2-4-Br 5-Br H O -CH2CH2CH2cH2cH2-. 2 5 4-OCF3 S-Br 8 O -CH2CH2CH2cH2cH2 4-CF3 5-Cl ~ O -CH2CH2CH2cH2cH2 .~. 4-C1 5-CI H O -cH2cH2cH2cH2cH2 4-Br 5-Cl H O -C82CH2CH2CH2cH2 . 4-CF3 5-CF3 H o -CH2CH2CH2cH2cH2-3 o 4-CF3 i-F H O -CH2CH2CH2cH2cH2-. 4-CF3 H H O -CN2CH2CH2cH2cH2-:: 4-CF3 5-13r ~:02Me O _C~i2C~2CH2CH2cH2-4-CF3 5-Cl CO2Me O -CH2C~2CB2cH2cH2-4-CF3 5-CF3 CO2Me O -CH2C~2CH2cH2c~2-3 5 3 CO2Me O -CN2CH2C~2cH2cH2-; 4-CF3 H CO2Me O -CH2CH2CH2cH2cH2-4-CF3 5-Cl H S -cH2cH2cH2cH2cH2 .,' .
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21~0(~130 Rl R2 B Y R8 R12 _.
4-C1 5-Cl H S -CH2CN2CH2cH2cH2-4-Br S-Cl H 5 -CH2CH2CH2CH2cH2-4-CF35-Br H S -cH2c~2cH2cH2cH2-; 4-CF35-F H S -CH2CH2CH2cH2cH2-4-CF34-Cl H S -CH2CH2CH2cH2cH2 4 CF34-F H S -CH2CH2CH2cH2cH2 : q-CF3 H H S -CH2CH2CH2cH2cH2 4-CF35-Cl C02Me ~ -cHzcH2cH2cH2cH2 4-CF35-Br C2Me S -CH2CH2CH2CH2CH2_ 4 CF35 F C2M~ S -CH2CH2CH2CH2CH2_ 9-CF34-Cl C02Me S -CH2CH2CH2CH2CH2_ 4_CF34_F C02Me ~ -CH2CH2CH2cH2cH2-:; 4-CF3 H C02Me S -CH2CH2CH2cH2cH2-4-CF35-Br H O -CH2CH20CB2cH2-4-C15-Br H O -CH2cN20cH2cH2 4-Br 5-Br H O -CH2cH20cH2cH2 . 4-OCF35-Br H O -CH2CH20CH2CH2 4-CF35-~1 H O -CH2CH20CH2cH2 4-C15-Cl ~ O -CH2cH20cH2cH2 i 25 4-Br 5-Cl H O -CH2CH20CH2cH2 '` 4-CF35-CF3 H O -CH2cH20cH2cH2 . 4-CF34-F H O -CH2CH20CH2cH2-4-CF3 H H O -CH2CH20CH2cH2 4-CF35-Br C02Me -CH2CH20CH2CH2-. . 30 4-CF35-cl co2Me O -CH2CH20CH2c~2-4-CF35-CF3 C02Me o -CH2cH20~H2cH2 4-C~34-F C02Me -cH2cH2ocH2cN2 4-CF3 H C02Me O -CH2cH20cH2cH2 4-CF35-Cl N S -CH2C~20C~2cH2 4-Cl S-Cl H S -CH2cH20cH2c~2 4-Br 5-Cl H S -CN2CN20CH2CH~
4-CF35-i3r H S -CH2CH20CH2CH2_ Z1~ 30 Rl R2 B V Re R12 ~
4-CF34-C18 S -CH2CH20~H2CH2_ ~
4-CF34-F H S -CH2CH20CH2cH2 4-CF3 H B S -C~zCH20C~2C82-4-CF35-Cl CO2Me S -CH2CH20CH2cH2 . 10 4-CF35-Br CO2Me S -CH2CH20CH2CH2-: 4-CF35-F CO2Me S -CH2CH20CH2cH2-4-CF34-Cl CO2Me S -CH2CH20CH2CH2_ ~ .
4-C~34-F C02Me S -CH2cH20c~2cB2 4-CF3 H CO2Me S -CH2cH20cH2cH2-4-CF35-Br H O -CH2CNMeOCHMeCH2_ 4-C15-Br H O -CH2CHMeOCHMeCH2-4-Br 5-Br H O -CH2CHMeOCHMeCH2_ 4-OCF35-Br H O -CH2CHMeOCHMeCH2-`~ 4-CF35-Cl H O -CH2CHMeOCHMeCH2-;' 20 4-C15-Cl H O -CH2CHMeOCHMeCH2-4-Br 5-Cl H O -CH2CWeOCHMeCH2_ : -. 4-CF35-CF3 H O -CH2CHMeOCHMeCH2-,~ 4-CF34-F H O -CH2CHMeOCHMeCH2- .
. 4-CF3 H H O -CH2CHMeOCXMeCB2_ ,,.
4-CF35-Br CO2Me O -CH2CNMeOCHMeCH2-4-CF35-Cl CO2Me O -CH2CWeOCHMeCH2_ 4-CF35-CF3 CO2Me O -CH2CHMeOCHMeCH2-:
4-CF34-F CO2Me -CH2CHMeOCHMeCH2- :
4-CF3 H ,C02Me -CH2CHMeOCHMeCH2-30 4-CF35-Cl ~ S -CH2CWeOCHMeCH2-i 4-C15-Cl ~ S -CHzCHMeOCHMeCH2-: 4-~r 5-Cl H S -CB2CHMeOCHMeCH2-4-CF35-Br H S -CH2CHMeOCHMeCH2_ .~ 4-CF35-F H S -CH2CHMeOCHMeCH2 4-CF34-Cl H S -CH2CWeOCHMeCH2-4-C~34-F H 5 -CH2CHMeOCHMeCH2-'t ., ~
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4-CF3 H H S -CH2C~MeOCHMeCH2-4-CF35-Cl C02Me S -CH2CHMeOCHMeCH2-4-CF35-Br ~02Me S -CH2CHMeOCHMeCH2-4 C~35-F C02Me ~ -CH2CHMeOCHMeCH2-4-CF3 ~-Cl CO2M~ S -CH2CHMeOCHMeCH2-4-CF34-F C02Me S -CH2CHMeOCHMeCH2-4-CF3 H C02Me S -CH2CHMeOCHMeCH2-4-CF35-Br H O ~t c 4-C15-Fr H O ~t cyclo-C6H
-- 15 4-Br 5-Rr H O Et cyclo-c6 ,.1 4-OCF35-Br H O Et cyclo-C6H
4-CF35-Cl H O Et 4-C15-Cl H O Et 4-Br 5-Cl H O Et cyclo-C6H
.~ 20 4-CF35-CF3 H o Et cyclo-c6H
4-C~34-F H O Et cyclo C6H
4-CF3 H N O Et cyclo-C
4-CF35-Br CO2Me Et Cyclo-c6H
~-CF35-Cl C02Me ~t Cyclo-c6Hll 4-CF35-CF3 co2Me O Et cyclo-C6H
. . 4-CF3 ~-F CO2Me Bt cyclo-C6H
4-CF3 ~ CO2Me Et cyclo-C6H
4-CF35-CI H S Et cYClo-C6H
4-C15-Cl H S Et ~YCl~~6Hll 4-Br 5-Cl H S Et cyclo-C6H
. 4-CF35-Br H S Et cyclo-C6H
4-CF35-F H S Et cyclo-C6H
4-CF34-Cl H S Et cyclo-C6H
~F34-E H S Et CYC1~
4-Cr3 H H 5 Et ~YCl-c6Nll 4-CF35-~1 c02Me S Et CYC1-C6Hll .', . ' .
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~28 Rl R2 El V R8 R12 4-CF3 5-Br C02Me S Et Cyelo-c6H
4-CF3 5-F CO2Me S Et ~yclo-C6H
4-CF3 4-Cl CO2Me S Et cyclo-c6 4-CF3 4-F CO2Me S Et c ~S-CF3 H C02Me S E;t CYC1-4-CF3 5-Elr B t) iPr CN2CH2C2Et :. 4-Cl S-Br H O iPr CH2CH2C2Et 4-Br 5-Br H O iPr t H2CH2C2Et 4-OCF3 5-Fr H O iPr CH2CH2CO2Et `: 15 4-CF3 5-Cl H O iPr CH2CH2CO2Et 4-C1 5-Cl H O iPr CHZCH2CO2Et 4-Br S-Cl H O iPr CH2CH2CO2Et 4-CF3 5-CF3 H O iPr CH2CH2C2Et 4-CF3 4-F H O iPr CHZ~H2CO2Et 2 0 4-CF3 H H O iPr CHZCH2CO2Et 4-CF3 5-Br CO2Me iPr CH2CH2CO2Et 4-CF3 5-Cl CO2Me O ~Pr CH2CH2CO2Et 4-CF3 5-CF3 CO2Me O iPr CH2CH2C2Et 4-CF3 4-F CO2Me iPr CH2CH2~2Et 2 5 4-CF3 H CO2Me iPr CH2CH2CO2Et 4-CF3 5-Cl H S iPr CHZCH2CO2Et 4-C1 5-Cl H S iPr CH2CH2C2Et ` 4-Br 5-Cl H S iPr CH2CH2C2Et 4-CF3 5-Br H S iPr CH2CH2C2Et 3 0 4-CF3 5-F H S iPr CH2CH2CO2Et 4-CF3 4-CI H S iPr CHZCH2EO2Et 4-CF3 4-F H S iPr CN2CH2CO2Et -,: 4-CF3 H H S iPr CH2CH2CO2Et 4-C~3 5-Cl CO2Me S iPr CH2CN2CO2Et 3 5 'I-CF~ 5-Br CO2Me S iPr CNZCH2CO2Et 4-CE3 5-F CO2Me S iPr CH2CHzCO2Et , ".
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Z~ 0130 12g .
Rl R2 B V R8 R12 4-CF3 4-Cl CO2Me S iPr CH2CH2C2Et . 4-CE3 4-F CO2Me S ~Pr CH2CH2CO2E~
4-CF3 H CO2Me S . ~Pr CH2CH2CO2Et :
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.. 20 Rl R2 ~ V Rlo :. 4-CF3 5-Br H O tBu .
-Cl 5-Br H O tBu 4-Br 5-Br H O tBu ::
254-OCF3 5-8r H O tBu 4-CF3 5-Cl H O tBu -~ 4-C1 5-Cl H O tBu ~ 4-Br 5-Cl H O tBu - 4-CF3 5-CF3 H O tBu 304-CF3 4-F H O tBu -j, 4-CF3 H H O t~u 4-~F3 5-Br CO2Me O tBu q-CF3 5-Cl CO2Me t~u 4-CF3 5-CF3 CO2Me O tBu , 35 ~-CF3 4-F CO2~e tBu . ~:
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2~(~Q130 Rl R2 ~ V Rlo 5 .
4-CF3 H C02Me tBu 4-CF3 5-Cl H S ~Bu 4-C1 5-Cl H S tElu 4-Br 5-Cl H S ti3u 4-CF3 5-Br H S tBu 4-CF3 5-F H S tBu 4-CF3 4-Cl H ~; tBu 4-CF3 4-E` ~i S tBu 4-CF3 H H S tElu 4-CF3 5-Cl C02Me S tBu 4-CF3 5-~r CO2Me S tBu 4 CF3 5-F CO2Me S tBu 4-CF3 ~-Cl CO2Me S tBu ~ 4-CF3 4-F CO2Me S tBu ,~ 20 4-CF3 N CO2Me S tBu - 4-Br 5-C1 H ' S cec-Bu 4-CF3 5-Br H S sec-Bu 4-CF3 5-F H 5 c~c-Bu - 4-CF3 4-Cl H S sec-Bu 2 5 4-CF3 4-F H S sec-Bu 4-CF3 H H S sec-Bu 4-CFj S-Cl CO2Me S sec-Bu .' q-CF3 5-Br CO2Me S sec-Bu 4-CF3 5-F C02Me S cec-Elu C 9 CF3 4-Cl CO2Me S ~c-Bu ` 4-CF3 4-F C02~e S e~c-llu , 4-CF3 H CO2Me 5 sec-Bu 4-CF3 5-Br N O Ph 4-C1 5-Br H O Ph 4-Br 5-llr H O Ph 4-OCF3 5-Br H O Ph .. . .
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2 _ V Rlo 4-CP3 S-Cl H O Ph 4-C1 5-Cl H O Ph 4-Br 5-Cl H O Ph 4-CF3 5-CF3 H o Ph 4-CF3 4-F H O Ph 4-CF3 H H O Ph 4-CF3 S-~r CO2Me Ph ~.
4-CF3 5-Cl CO2Me Ph :~ 4-CF3 5-CF3 CO2Me o Ph 4 CF3 4-F CO2Me Ph 4-CF3 H CO2Me Ph 4-CF3 5-Cl H S Ph , 4-Cl S-Cl H S Ph 4-Br 5-Cl H S Ph :~ 2 0 4-CF3 5-Br N S Ph ;~ 4-CF3 5-F H S Ph 4-CF3 4-C1 0 S Ph , 4-CF3 4-F H S Ph . 4-CF3 H H S Ph :'. 2 5 4-CF3 5-Cl CO2Me S Ph ^ 4-CF3 5-Br CO2Me S Ph 4-CF3 5-F CO2Me S Ph .;~ 4-CF3 4-Cl CO2Me S Ph s~ 4 CF3 4 F Ç02Me S Ph 3 o 4-CF3 H CO2Me S Ph 4-CF3 5-Br S~ O ~-Cl-Ph .` 4-C1 5-Br H O 4-Cl-Ph 4-~r 5-Br H O 4-Cl-Ph 4-OCF3 5-~r H O 4-Cl-Ph 3 5 4-C~3 5-Cl H O 4-Cl-Ph 4-C1 5-C1 11 0 4-Cl-Ph .. . ..
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Rl R2 B V Rlo 4-8r 5-Cl H O 4-Cl-Ph 4-CF35-CF3 H o ~-Cl-Ph 4-CF34-F H O 4-Cl-Ph 4-CF3 ~ H O 4-Cl-Ph 4-CF35-Br CO2Me 4-Cl-Ph 4~CF35~cl CO2Me 4-Cl-Ph 4-CF35-CF3 CO2Me O 4-Cl-Ph 4-CF34-F CO2~e ~ 4-~1-Ph 4-CF3 H CO2Me O 4-Cl-Ph 4-CF35-Cl H S4-Cl-Ph 4-C15-Cl H S4-Cl-Ph 4-Br 5-Cl H S4-Cl-Ph 4-CF35-Br H S4-Cl-Ph 4-CF35-F H S4-Cl-Ph 4-CF34-Cl H S4-Cl-Ph 4-CF34-F ~ S4-Cl-Ph 4-CF3 H H S4-Cl-Ph .~ 4-CF35-Cl CO2Me S4-Cl-Ph . 4-CF35-Br CO2Me S4-Cl-Ph . 25 4-CF35-F CO2Me S4-Cl-Ph i~ 4-CF34-Cl CO2Me S4-Cl-Ph 4-CF34-F CO2Me S 4-Cl-Ph 4-CF3 H CO2Me S 4-Cl-Ph ?0 ": . ,:
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~',!j 20 ~1 R2 Rl3a 13 ~ - R8 Rg E 4-CF3 5-F Me Me S Me OEt . 4-CF3 5-Cl Me Me S Me OEt 7 . 4-CF3 4-F Me Me S Me OEt ., 25 4 CF3 S-Br Ph H O Me OEt 4-CF3 5-Br CO2Me H o Me OEt 4-CF3 S-Br Me Me O Me OEt :~ 4-CF3 5-Cl Me Me O Me OEt 4-CF3 S-F Me Me S Me O-nBu ~ 30 4-CF3 S-Cl Me Me S Me O-nBu :~
". 4-CF3 4-F Me Me S Me O-nBu 4-CF3 S-Br Ph ~ O Me O-~Bu ~-CF3 5-Fr CO2Me H O Me O-nBu 4-CF3 S-~r Me Me O Me O-n9u ~-CF3 S-Cl Me Me O Me O-nBu .
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135 .:
Rl R2 R 3~ R b V R8 Rg , - . .
4-CF35-F Me Me S Me O-DHeryl 4-CF35-Cl Me Me ~ Me O-nHesyl 4-CF34-F Me Me S Me O-nBe~yl 4-CF35-Br Ph H O Me O-nHe~yl . 10 4-CF35-Br C02Me H O Me O-~He~yl 4-CF35-Br Me Me O Me O-nHe~yl 4-CF35-Cl Me Me O Me O-nHexyl 4-CF35-F Me Me 6 Me O-~ec-9u 4-CF35-Cl Me Me S Me O-sec-Bu 4-C}34-F Me Me S Me O-oec-Bu 4-CF35-Br Ph H O Me 0-6ec-Bu 4-CF35-Br C02Me H O Me O-see-Bu 4-CF35-Br Me Me O Me O-sec-Bu 4-CF35-Cl Me Me O Me O-~ec-Bu :~.
4-C~35-F Me Me S Me O-lPr 4-CF35-Cl Me, Me S Me O-lPr .:~
4-CF34-F Me Me S Me O-iPr . 4-CF35-Br Ph H O Me O-lPr 2 4-CF35-Br C02Me H O Me O-iPr -` 25 4-CF35-Br Me Me O Me O-iPr .
4-CF35-Cl Me Me O Me O-iPr 4-CF35-F Me Me S Me OCH2CH20Et 4-CF35-Cl Me Me S Me OCH2CH20Et 4-CF34-F Me Me S Me OCH2CH20Et 4-CF35-9r Ph H O Me OCH2CH20Et .j 4-CF35-Br C02Me H O Me OCH2CH20Et 4-CF35-Br Me Me O Me . OCH2CH20Et ,- 4-CF35-Cl Me Me O Me OCH2CN20Et : 4-CF35-F Me Me S Me F
3S 4-CF35-Cl Me He S Me F
:~ 4-CF34-F Me Me S Me ,'' . ~ ~,:
. . ~
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2~ 30 R2 R13~ R b V R8 Rg 4-CF35-Br Ph H O Me . F
4-C~35-Br CO2Me H O t~5e F
4-CF35-l~r l~le ~e O Me F
. ~ 4-CF35-Cl ~e Me O Me F
4-C~35-F Me Me 6 Me NMe2 4-CF35-Cl Me Me S Me NMe2 : 4-CF34-F Me Me S Me NMe2 4-CF35-Br Ph H 0 ~le NMe2 4-CF35-~r CO2Me H O Me NMe2 4-CF3 5-Br Me Me 0 ~5e NMe2 4-CF3 5-Cl Me Me O Me NMe2 4-CF3 5-F Me Me S Et O-iPr 4-CF3 5-Cl Me Me S Et O-iPr 4-CF3 4-F Me Me S Et O-iPr 4 -CF35-Br Ph H O Et O-iPr 4-CF35-Br CO2Me H O Et O-iPr 4-CF35-Br Me Me O Ct O-iPr ~:
4-CF3 5-Cl Me Me O Et O-iPr 4-CF3 5-F Me Me S iPr OEt :
4 -CF3 5-Cl Me Me S iPr OEt .. 4-CF3 4-F Me Me S iPr OEt 4-CF3 5-Br Ph H O iPr OEt ~,~ 4-CF3 5-Br CO2Me H O iPr OEt 4-CF3 5-Elr Me Me O iPr OEt 4 -CF35-Cl Me Me O iPr ClEt 4-CF35-F Me Me S iPr OCH2CF3 4-CF35-Cl Me Me S iPr CIJ2CF3 :. q-CF34-F Me Me S iPr OCH2cF3 4-CF35-Br P~ H O ~Pr OCH2cF3 35 4-CF35-Br C02Me H O iPr C~CH2~r3 4-CF35-Br Me Me O iPr OCH2CF3 ., .
, .. . .. ..
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2~ Ql;~O
R2 R13 Rl3b V R8 Rg 4-CF3 5-Cl Me Me O lPr OCH2CF3 4-CF3 5-F Me Me ~ 1Pr OCH2C02Me ~ 4-CF3 S-Cl Me Me S lPr OCH2C2Me : 4-CF3 4-F Me Me S ~Pr OCH2C02Me 4-CF3 5-Br Ph H O ~Pr OCH2C02Me 4-CF3 5-Br C02Me H O ~Pr OCH2CO~Me : 4-CF3 S-Pr ~e Me O iPr OCH2C02Me 4-CF3 5-Cl Me Me O lPr OCH2C02Me ` 15 . .
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: '~ 2 5 4 -CF3 4-Cl N Me OEt 4-C1 4-Cl H Me OEt i 4-Br 4-Cl H Me OEt .'. 4-OCF3 4-Cl H Me OEt 4-OC~2N 4-Cl H Me OEt 3'4-CH2C(Me)2O 4-Cl H Me OEt 4-CF3 4-F H Me OEt ~` 4-C1 4-F H Me OEt 4-Er 4-F H Me OEt 4-OC~3 4-F H Me OEt 4-ocr2~ 4-F H lle OEt 3S 3,4-CH2C~Me)20 4-F H Me OEt . ' :
'''' ' ' 2~ 30 Rl R2 k3 R8 R9 4-CF 4-OCF2H H Me OEt 4-C1 4-OCF2H ~ Me OEt ~-8r 4-OCF2H H Me OEt ~: ~-OCF3 ~-OCF2H ~ Me OEt 4-OCF2H ~-OCF2H B Me OEt 3,4-CH2C~Me)20 4-OCF HB Me OEt 4-CF3 4-Br H Me OEt 4-CF3 4-C1 4-Cl Me OEt 4-C~ 4-C1 4-Cl Me OEt 4-Br 4-C1 4-Cl Me OEt : 15 4-OCF3 4-C1 4-Cl Me OEt :` 4-OCF2H 4-C1 4-Cl Me OEt 3,4-CH2C(Me)20 4-C1 4-Cl Me OEt 4-CF3 4-F 4-Cl Me OEt ~- 4-OCF3 4-F 4-Cl Me OEt 4-CF3 4-OCF2H 4-Cl Me OEt 4-OCF3 4-OCF2H 4-Cl Me OEt ~ 4-CF3 4-C1 4-CN Me OEt : :
2 4-C1 4-C1 4-CN Me OEt ,c. 4-OCF3 4-C1 4-CN Me OEt :.
4-CF3 4-F 4-CN Me OEt 4-OCF3 4-F 4-CN Me OEt , 4-CF3 .4-C1 4-CO2MeMe OEt 'j` 4-CF3 4-Cl H Me O-n-Bu ~ 4-OCF3 4-Cl H Me O-n-8u '' 30 4-CF3 4-F H Me O-n-8u : 4-OCF3 4-F H ~e O-n-Hu ;: .
:~ 3,4-CH2C(Me)20 4-F H Me O-n-Bu :.
; 4-CF3 4-OCF2H H he O-J-Bu : 4-C1 4-OCF2H B Me O-n-8u ~ .
4-~r 4-ocr2~ ~ ~e '~,".;
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Rl R2 ~3 R8 ~9 _ . _ 4-OCF3 4-CF2H H Me O-D-BU
4-CF3 4-Br H M~ O-n-Bu 4-CF3 4-C1 4-Cl Me O-n-Bu 4-C1 4-C1 4-Cl Me O-n-Bu 4-Br 4-C1 4-Cl Me O-n-Bu 4-OCF3 ~-Cl ~-Cl Me O-u-Bu 4-CF3 4-F d-Cl Me O-n-Bu 4-OCF3 4-F 4-Cl Me O-n-Bu 4-CF3 4-OCF2R 4-Cl Me O-n-Bu 4-C1 4-OCF2N 4-CI Me O-n-Bu 4-Br 4-OCF2H 4-Cl Me O_~-Bu 4-OCF3 4-OCF2H 4-Cl Me O-n-Bu 4-CF3 4-C1 4-CN Me O-D-BU
- 4-OCF3 4-C1 4-CN Me O-D-Bu ~- 4-CF3 4-F 4-CN Me O-n-Bu .. 20 4-OCF3 4-F 4-CN Me O-n-Bu 4-C1 4-C02Me Me O-n-Bu 4-CF3 4-OMe 4-Cl Me O-n-Bu 4-C1 4-OPh 4-Cl Me O-n-Bu 4-Br 4-SCF H 4-Cl Me O-n-Bu 4^0CF3 4-N02 4-Cl Me O-n-Bu 4-OCF2~ 4-5Me 4-Cl Me O-n-Bu ~ 3,4-CH2C(Me)20 4-S02Me 4-Cl Me O-n-Bu .,. 4-CF3 4-CN 4-Cl Me O n-Bu - 4-Cl - 3-C1 4-Cl Me O-n-Bu ,~
4-Br 3-F 4-CI Me O-n-Bu ; 4-OCF3 4-Me 4-Cl Me. O-n-~u 4-OCF2H 4-allyl 4-Cl ~e O-D-~U
2 ( )2 4-CF3 4-Cl Me O-n-Bu ;' 4-CF3 -Cl 4-C02Et ~e O-~-Bu '' ' -, .
, , .
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2~(~()130 Rl R2 R3 R8 Rg 4-Cl q-Cl ~-aMe Me O-n-Bu 4-Br 4-C1 4 SCF2CF2H Me O-n-Bu '-4-OCF3 4-Cl ~ CF2CF2H Me O-n-~u 4-OCF2H 4-Cl ~-OPh Me O-n-Bu 3~4-cN2c(Me)2o 4-CF3 q-CF3 Me O-n-}3u 4-CF3 4-C1 4-CF3 Me O-n-Bu 4-C1 4-C1 4-Me Me .O-n-Bu 4-Br 4-C1 3-Cl Me O-D-Bu 4-OCF3 4-C1 3-~r ~e O-D-Bu 4-OCF2H 4-C1 4-NO2 Me O-n-~u 4-CF3 4-Cl H Me O-n-hexyl 4-CF3 4-F H Me O-n-he~yl 4-CF 4-OCF2H H Me O-n-he~yl 4-OCF3 4-OCF2N H Me O-n-octyl 4-CF3 4-Br R Me O-n-octyl 4-CF3 4-C1 4-Cl Me O-n-octyl 4-Cl .4-C1 4-Cl Me O-n-octyl 4-}3r 4-C1 4-Cl Me O-n-octyl 4-OCF3 4-C1 4-Cl Me O-n-octyl . --4-CF3 4-F 4-Cl Me O-n-decyl -4-C1 4-F 4-Cl Me O-n-decyl . -4-OCF3 4-F 4-Cl Me O-n-decyl 4-CF3 4-OCF2H 4-Cl Me O-n-decyl .: 4-OCF3 4-OCF2H 4-Cl Me O-n-decyl ~::
,~ 30 4 C 3 4-C1 4-CN Me O-n-decyl . 4-C1 4-C1 4-CN Me O-n-~eeyl 4-Br 4-Cl 4-CN Me O-n-decyl 4-OCF3 4-C1 4-CN Me O-n-dodecyl 4-CF3 ~-r 4-CN Me O-n-dodecyl 4 3 4-r 4-CN Me O-D-dOdeCY1 ~-CF3 4-Cl 9-CO2Me Me O-n-dodecyl 4-CF3 4-Cl H Me O-sec-Bu 4-C1 4-Cl N Me O-sec-Bu ; .
.: .; ' .. . .
Z~0~3~1 :
~42 Rl R2 ~3 R8 Rg 4-OCF3 q-Cl ~ Me O-c~c-Bu 3 4-~ H Me O-sec-Bu 4-OCF3 4-r ~ Me O-cec-Bu 4-CF3 4-OCF2H H Me O-c~c-Bu 4-OCF3 ~-OCF2H ~I Me O-cec-~u 4-CF3 4-9r H Me O-sec-8u 4-CF3 4-Cl ~-Cl Me O-~ec-Bu 4-C1 4-C1 4-Cl Me O-cec-~u ~ 4-Br 4-C1 4-Cl Me 0-6ec-Bu : 4-OCF3 4-C1 4-Cl Me O-cec-Bu 4-CF3 4-F 4-Cl Me 0-6ec-Bu 4-C1 4-F 4-Cl Me O-oec-Bu 4-OCF3 4-F 4-Cl Me O-cec-Bu 4-CF3 4-OCF2H 4-Cl Me O-~ec-Bu .~ 4-OCF3 4-OCF2H 4-Cl Me O-sec-Bu.
~, 20 4-CF3 4-C1 4-CN Me 0-6ec-Bu : 4-C1 4-C1 4-CN Me O-Lec-Bu 4-OCF3 4-C1 4-CN Me O-~ec-Bu 4-CF3 4-F 4-CN Me O-~ec-Bu 4-OCF3 4-F 4-CN ~e O-~ec-Bu '` 25 4-CF3 4-C1 4-C02Me Me O-eec-Bu 4-CF3 4-CN 4-Cl Mc O-sec-Bu .; 4-C1 3-C1 4-Cl Me 0-6ec-Bu " 4-Br 3-F 4-CI Me O-~ec-Bu , 4-OC~3 ~-~e 4-Cl Me O-~ec-Bu 4-CF3 4-C1 4-CO2~t Me O-~ec-Bu ~` 30 4-C1 4-Cl q-OMe Me O-~ec-~u 4-9r 4-C1 2 2 O-sec-Bu ~ 4-OCF3 4-CI ~-Cr2cF2H Me O-rec-Bu " 4-OCF2 4-C1 4-OPh Me O---c-~u 3,4-CH C(Me) O 4-C1 6-CF3 Me O-~oc-Pu , 4 CF3 4-C1 4-CF3 Ue O-cec-Bu 4-C1 4-C1 4-Me Me O-cec-Bu , ~ ' ,: ' ., .~
Z(~(~013~) Rl R2 R3 X8 R~
4--Br 4-Cl ~-Cl Me O--ec-Bu 4-OCF3 4-C1 3-Br Me O-cec-Bu 4-OCF2H 4-Cl ~-NOz Me O-sec-Bu 4-CF3 ~-Cl H ~e O-~Pr . 4-OCF3 4-Cl H Me O-~Pr :~ 10 4-CF3 4-F H Me O-~Pr 4-OCF3 4-F H Me O-iPr ; 4-CF3 4-OCF2H H Me O-iPr ~ 4-OCF3 4-OCF2H H Me O-iPr : 4-CF3 4-Br H Me O-lPr 4-OCF3 4-Br H Me O-iPr 4-CF 4-C1 4-Cl Me O-iPr - 4-OCF3 4-C1 4-Cl Me O-iPr ~-4-CF3 4-F 4-Cl Me O-~Pr , ~
4-OCF3 4-F 4-Cl Me O-lPr ' ~:
4-CF3 4-Cl q-CN Me O-iPr 4-OCF3 4-C1 4-CN. Me O-~Pr 4-CF3 4-F 4-CN Me O-iPr `~
4-OCF3 4-F 4-CN Me O-iPr ' 25 4-CF3 4-C1 4-CO2MeMe O-~Pr ;, 4-CF3 4-Cl N Me OCH2CH20Et 4-CF 4-F H ~e 2 Z
4-CF 4-OCF2H H Me 2 2 : 4-OCF3 4-OCF2H H Me OCH2ccl3 3 ~-Br H Me OCH2ccl3 4-~F3 q-CI q-Cl Me OCH2CCl 4-C1 4-C1 6-Sl Me OCH2ccl3 : 4-OCF3 ~-Cl 4-Cl Me OCH2ccl3 .~ 4-CF3 4-F 4-Cl Me OCH2CF3 ., 4-OCF3 ~-F 4-Cl . 2 3 4-CF3 4-OCF2H 9-Cl ~e :
.:
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Rl R2 R3 R8 R9 .
4-oCF3 4-OCF2H ~-Cl ,. Me ~H2CF3 4-CF3 q-Cl 4-CN Me 2 3 4-OCF3 4-Cl l-CN Me OCN2C02Et 4-CF3 4-F ~-CN He OCH2CO2Et 4-OCF3 4_~ ~-CN Me OCH2CO2Et 4-~r3 4-C1 4-CO2Me Me OCH2CO2Et 4-CF3 4-Cl H Me F
4-Cl ~-Cl B Me F
4-OCF3 4-Cl R Me F
: 4-CF3 4-F ~ Me F
4-OCF3 4-F H Me F
4-CF3 4-OCF2H H Me F
4-OCF3 4-OCF2N H Me NMe2 4-CF3 4-Br H Me NMe2 ~` 20 4-CF3 4-C1 4-Cl Me NMe2 4-C1 4-C1 4-Cl Me NMe2 :~: 4-OCF3 4-C1 4-Cl Me MMe2 4-CF3 4-F 4-Cl Me NEt2 ~-OCF3 4-F 4-Cl Me NEt ' 25 4-CF3 4-OCF2H 4-Cl Me piperidino .i 4-OCF3 4-OCF2N 4-Cl Me morpholl~o 4-CF3 4-C1 4-CN Me n-Pr 4-OCF3 4-C1 4-CN Me n-Pr . 4-CF3 4-F 4-CN Me Sec-Bu " 4-OCF ~-F 4-CN Me 4-Cl-Pb .~ ~-CF3 4-Cl ~-CO2Me Me Ph ~- 4-CF3 4-Cl H Et O-iPr ~-Cl 4-Cl H Et O-~Pr 4-OÇF3 4-Cl N Et O-lPr 4-ÇF3 4-F H Et O-lPr ~-OCF3 4-F H Et O-~Pr 4-CF3 ~-OCF2N H Et O-~Pr ' ~ ' .
- . .
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:. . .. .~ . . . ; . :
2~VQ~3C) Rl ~2 ~3 R8 Rg 5..
4-OCF3 A-OCF2H H Et O-~Pr 4-CF3 ~-Br H ~t O-iPr 4-CF3 4-Cl . 4-Cl Et - O-~Pr 4-OCF3 4-C1 4-Cl Et O-~Pr 4-CF3 4-~ q-Cl Et OEt : 4-OCF3 4-F 4-Cl ~t OEt . 4-CF3 4-OCF2H 4-Cl Et ocH2ccl3 ~
: 4-OCF3 4-OCF2H 4-CI Bt 2 4-CF3 4-Cl 4-CN Et 2,6-~i-Me-morpholino 4-OCF3 4-C1 4-CN Et 2,6-di-Me-morpholino 4-CF3 4-F 4-CN Et iPr 4-OCF3 4-F 4-CN Et Ph 3,4-CH2C(Me)20 4-F 4-CN Et Ph - 4-CF3 4-Cl H lPr OEt .
~0 4-OCF3 4-Cl H iPr OEt 4-CF3 4-F H lPr OEt ~ 4-CF3 4-OCF2H H iPr OEt .
; 4-OCF3 4-OCF2H H lPr OEt . 4-CF3 4-Br H iPr OEt : 25 4-CF3 4-C1 4-Cl ~Pr OEt .~ 4-C1 4-C1 4-Cl iPr OEt 4-Br 4-C1 4-Cl iPr OEt 4-OCF3 4-C1 4-Cl iPr OEt !:.
j 4-CF3 4-E 4-Cl iPr OEt 30 4-OCF3 4-F q-Cl iPr OEt ,:
4-CF3 4-OCF2H 4-Cl iPr OEt 4-OCF3 4-OCF2~ 4-Cl iPr OEt . 4-CF3 4-C1 4-CN lPr OEt .:
4-OCF3 4-C1 4-CN lPr OEt 4-CF3 4-F 4-CN lPr OEt ~';"' ,' ':
7; ' . :
.. ':
Z~ ?13~3 .
~1 R2 R3 R8 Rg 4-OCF3 4-F 4-CN lPr. OEt 4-CF 4-C1 4-CO2Me iPr OEt 4-CF3 4-CN 4-Cl iPr OEt 4-C1 3-C1 4-Cl lPr OEt 4-8r 3-F 4-Cl iPr OBt 4-OCF3 4-Me 4-Cl iPr OEt 4-OCF2H 4-~-ullyl 4-Cl lPr OEt 3,4-CH2C(Me)2O 4-CF3 4-Cl iPr OEt 4-CF3 4-C1 4-CO2Et iPr OEt .: 15 4-C1 4-C1 4-OMe ~Pr OEt - 4-Br 4-C1 4-SCF2CF2H iPr OEt 4-OCF3 4-C1 2 2 iPr OEt 4-OCF2H 4-C1 4-OPh iPr OEt 3,4-CH2C(Me)2O 4-C1 4-CF3 iPr OE~
.- 20 4-C~3 4-C1 4-CF3 iPr OEt ~ 4-Br 4-C1 3-Cl iPr OEt .. 4-OCF3 4-C1 3-Br iPr OEt ~ 4-OCF2H 4-C1 4-No2 iPr OEt .; 4-CF3 4-Cl H lPr O-n-Bu 25 4-C1 4-Cl H iPr O-n-Bu :~ 4-Br 4-Cl N iPr O-n-Bu 4-OCF3 4-Cl H iPr O-n-Bu ` 4-CF3 4-F H iPr O-n-Bu 4-OCF3 . 4-F H iPr O-n-Bu 4-C~3 4-OCF2H H iPr O-D-Bu ': 30 4-OCF3 4-OCF2H H i~r O-n-Bu ~-CF3 4-Br H iPr O-n-Bu 4-CF3 4-C1 4-Cl iPr O-n-Bu 4-Br 4-C1 4-Cl iPr O-n-0u 4-OCF3 4-C1 4-Cl iPr O-n-Bu 4-CF3 4-F 4-Cl iPr OCH2CF
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1~7 R3 119 - . _ 4-OCF3 4-r 4-Cl lPrCH2cF3 ~ 4-CF3 4-OCF2H 4-CllPr 2 2 : 4-OCF3 2 Cl lPr NMe~
4-CF3 4-C14-CN lPr 2 10 4-OCF3 4-C14-CN lPr 2 4-CF3 4-F 4-CN iPrpiperidino 4-OCF3 4-r 4-CN lPr Et 4-CF3 4-C1 4-CO2Me lPr Ph 3,4-CH2C(Me)2O 4-C1 4-CO2Me lPr Ph ; 15 4-CF3 4-Cl H CH2Ph OEt 4-CF3 4-OCF2H H CHzPh piperidiDo .; 4-CF3 4-~r H CH Ph OCH2CH2OEt : 4-CF3 4-C1 4-Cl CH2Ph Me . ,. .: .
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..
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. 20 R R2 R3 R8 Rg ~'' '.
.. i 4-CF3 4-Cl H Me 2 . 4 OCF3 4-Cl H Me 2 - - 25 4-CF3 4-F H MeNMe 4-OCF3 4-F H MeNMe2 . 4-OCF2H H MeNMe2 -~` 4-OCF3 4-OCF2H H MeNMe2 4-CF3 4-C1 4-Cl MeNMe2 4-C~ 4-C1 4-Cl Me 4-Br 4-C1 4-Cl MeNMe2 ~.
.~ 4-OCF3 4-C1 4-Cl Me 2 ., 4-CF3 4-F 4-Cl MeNMe2 ~i~
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Rl R2 R3 ~8 Rg _ 4-OCF3 ~_~ 4-Cl Me. NMe2 4-CF3 ~-OCF2H 4-Cl Me NMe2 ~ q-OCF3 4-OCF2H 4-Cl Me NMe2 .~ 4-CF3 4-C1 4-CN Me NMe 4-C1 4-C1 4-CN Me 2 4-Br ~-Cl 4-CN Me NMe2 4-OCF3 4-Cl ~ CN Me NMe 4-CF3 4-F 4-CN Me 2 : 4-OCE3 4-F 4-C~ Me 2 . 15 4-CF3 4-C1 2 NMe2 4-CF3 4-Cl H Me 2 :
3'4-CH2C(Me)2~ ~-Cl H Me 2 . 4-CF3 ~-F H Me 2 ~ 4-OCF3 4-F H Me 2 " 20 4-CF3 4-DCF2H H Me 4-OCF3 ~-DCF2H ~ Me NEt `' 9-CF ~-~r H Me 2 3,4-CH2C(Me)20 4-~3r H Me NEt2 4-CF3 4-S1 4-Cl Me 2 4-C1 4-D~ 4-Cl Me 2 ~! 4-Br 4-C~ 4-Cl MeNEt2 - 4-OCF3 4-C1 4-Cl Me 2 4-CF3 4-r 4-Cl MeNEt2 9-OCF3 44F 4-Cl Me NEt 4-OCF2H 4-Cl Me NEt 4-OCF3 4-~CF2H 4-Cl Me 4-OCF2N ~-DCF2H 4-Cl Me NEt2 3,4-CH2C~Me)20 ~-~CF2H 4-Cl Me 2 4-CF3 4-C1 4-CN Me NEt2 , 35 3 4_Cl 4-CN Me ~Et2 .~ :
, ;~
.,~, 2l~;~P0~30 Rl R2 R3 R8 R9 4-CF 4-F 4-CN Me 2 4-OCF3 4-F 4-CN Me NEt2 4-CF3 4-Cl H Me piperidino 4-OCF3 4-Cl H Me piperidiDo 4-CF3 4-F H Me Se~-Bu 4-OCF3 4-F H Me n-he~yl 4-CF 4-OCF2H H Me Ph ; 4-OCF3 4-OCF2H H Me Ph ` 15 4-CF3 4-Br H Me 4-Cl-Ph 4-C1 4-Br H Me 4-Cl-Ph 4-CF3 4-C1 4-Cl Me n-Bu 4-Cl 4-C1 4-Cl Me n-Bu 4-Br 4-C1 4-Cl Me n-Bu 4-OCF3 4-C1 4-Cl Me n-Bu 4-CF 4-F 4-Cl Et 2 : 4-OCF3 4-F 4-Cl Et 2 .:
4-CF3 4-OCF2H 4-Cl Et NEt2 4-OCF3 4-OCF2H 4-Cl Et morpholino 4-CF3 4-C1 4-CN Et lPr :
3,4-CH2C~Me)2O 4-C1 4-CN Et n-Bu ~ 4-CF3 4-F 4-CN Et n-Bu `
'; 4-CF 4-C1 2 4-MeO-Ph 4 CF 4-Cl H iPr 2 ` 30 4-C1 4-Cl H iPr NMe2 4-Br 4-Cl~ H iPr NMe2 4-oCF3 4-Cl H iPr NMe2 ` 4-CF 4-F H ~Pr NMe2 4-OCF3 4-F H ~Pr 2 4-CF3 4-OCF2H H iPr NMe2 4-OCF3 4-OCF2H H . iPr 2 '' ' ' ,:' :
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~ 1 R2 R3 R8 Rg . . , _ . . .
. :
3,4-CH2C~Me)~O 4-OCF2H H iPr NMe2 4-CF 4-Br H iPr NMe2 ~ 4-CF3 4-C1 4-Cl iPr 2 '.
; 4-C1 4-C1 4-Cl iPr NMe2 1~ 4-Br 4-C1 4-Cl iPr NMe2 4-OCF3 4-C1 4-CI lPr 2 4-CF 4-F 4-Cl ~Pr 2 :
4-OCF3 4-F 4-Cl iPr 2 4-CF3 4-OCF2H 4-Cl iPr 2,6-di-Me-morpholino : 15 4-OCF3 4-OCF2H 4-Cl iPr piperidino :
4-CF3 4-C1 4-CN iPr Et .,~ 4-OCF3 4-C1 4-CN iPr Et - 4-CF3 4-F 4-CN iPr n-Bu 4-OCF3 4-F 4-CN iPr Ph ' 4-CF3 4-C1 4-CO2Me iPr 4-Cl-Ph ' ~- .
`...... ~ 25 . ~ .
.,. :
.,'' ' ... .
:';
:
' , .','' ' , -., ; ' .:
2~lQ0l30 .
Iable 18 .
R~ 3 : o~ ~;
; I yl ':
S ~I ..
~N--p_y1 R
R~ Y~ R~
... .
, .
: ' :
A 20 Rl R2 R3 R8 yl YlR1o Y Rll 4-CF3 4-Cl H tBu S OEt OEt 4-OCF3 4-Cl H tBu S OEt OEt 4-CF3 4-F H tBu S OEt OEt ... 25 4-OCF3 4-F H tBu S OEt OEt ~ 3 g-OCF2H H tBu S OEt OEt -2~ 4-OCF3 4-OCF2H H tBu S OEt OEt .;. 4-CF3 4-Br H tBu S OEt OEt ~ 4-CF3 4-Cl 4-Cl tBu S OEt OEt "r 30 4-C1 4-C1 4-Cl tBu S OEt OEt .' 4-Br 4-C1 4-Cl tBu S OEt OEt 4-OCF3 4-C1 4-Cl tBu S OEt OEt 4-CF3 4-F 4-Cl tBu S OEt OEt 4-OCF3 4-F 4-Cl tBu S OEt OEt 4-CF 4-OCF2H 4-Cl tBu S OEt OEt 4-Br 4-OCF2H 4-Cl tBu S OEt OEt ..
' :
,!; ::,:, ':
,.
, . -. , ,. ,: : . -. : . , . . ,:- : . , , . .,. . . - . ..
q~3 0 1 R2 R3 R8 yl YlR1o Y Rll 4-OCF3 4-OCF2H 4-Cl tBu S OEt OEt 4-CF3 4-C1 4-CN tBu S OEt OEt 4-OCF3 4-C1 4-CN tBu S OEt OEt 4-CF3 4-F 4-CN tBu S OEt OEt 4-OCF3 4-F 4-CN tBu S OEt OEt 4-CF3 4-C1 4-CO2Me t8u S OEt OEt 4-CF3 4-Cl H tBu S OCH2C(Me)2CH2O
4-OCF3 4-Cl H t~u S OCH2C(Me)2CH2O
4-CF3 4-F. H tBu S OCH2C(Me)2CH2O
4-C1 4-F H tBu S OCH2C(Me)2CH2O
4-OCF3 4-F H tBu S OCH2c~Me)2cH2O
~-CF3 q-OCF2H H tBu S OCH2C(Me)2CH2O
4-oCF3 4-OCF2H H tBu S OCH2C(Me)2CH2O
4-CF3 4-Br H tBu S OCH2C(Me)2CH2O
4-CF3 4-C1 4-Cl tBu S OCH2C(Me)2CH2O
4-C1 4-C1 4-Cl tBu S OCN2C(Me)2CH2O
4-Br 4-C1 4-Cl tBu S OCH2C(Me)2CH2O
4-OCF3 4-C1 4-Cl tBu S OCH2C(Me)2CH2O
4-CF3 4-F 4-Cl tBu S OCH2C(Me)2CH2O
4-OCF3 4-F 4-Cl tBu S OCH2C(Me)2CH2O
4-CF3 4-OCF2H 4-Cl tBu S OCH2C(Me)2CH2O
4-OCF3 2 tBu S OCH2C(Me)2CH2O
4-CF3 4-C1 4-CN tBu S OCH2C(Me)2CH2O
4-OCF3 4-C1 4-CN tBu S OCH2C(Me)2CH2O
4-CF3 4-F 4-CN tBu S OCB2C(Me)2CH2O
30 4-OCF3 4-F 4-CN tEu S OCH2C(Me)2CH2O
4-CF3 4-C1 4-CO2Me tBu 2 ( )2 2 4-CF3 4-Cl H iPr S OEt OEt 4-C1 4-Cl H iPr S OEt OEt 4-OCF3 4-Cl H ~Pr S OEt OEt 4-CF3 4-F H iPr S OEt OEt 4-OCF3 4-F H iPr S OEt OEt ' , ' .'`, , .
..... ., ... ~., , .. ;... ,. .;, .,, . , ~ . :
, ' . ~ . , : :, ,',, . ' 21~Q(;~1.30 Rl R2 R3 P'8 yl Y
4-OCF2H H iPr ~ OEt OEt 4-OCF3 4-OCF2H H iPr S OEt OEt 4-C~3 4-Br H ~Pr S OEt OEt 4-CF3 4-C1 4-Cl iPr S OEt OEt 4-OCF3 4-C1 4-Cl iPr S OEt OEt 4-CF3 4-F 4-Cl iPr S OEt OEt 4-OCF3 4 F 4-Cl iPr S OEt OEt q-CF 4-OCF2H 4-Cl iPr S OEt OEt 4-OCF3 4-OCF2H 4-Cl iPr S OEt OEt .~ 4-CF3 4-C1 4-CN iPr S OEt OEt 4-OCF3 4-C1 4-CN iPr S OEt OEt 4-CF3 4-F 4-CN iPr S OEt OEt " 4-OCF3 4-F 4-CN iPr S OEt OEt 4-CF3 4-C1 4-CO2Me iPr S OEt OEt : 20 4-CF3 4-Cl H iPr S OCH2C(Me)2CH2O
. 4-OCF3 4-Cl ~ iPr S OCH2C(Me)2CH2O
, 4-CF3 4-F H iPr S OCH2C(Me)2CH2O
4-OCF3 4-F H iPr S OCH2C(Me)2CH2O
:
," ',:
. . .
~ 30 ~ ~ . ' ' ' .' .
~! `
' ~.
.
. :- ' Z~C~()130 4-CF3 4-OCF2H H iPr S OCH2C(Me)2CH20 .
4-CF3 4-Br H iPr S OCH2C(Me)2CH20 4-CF 4-C1 4-Cl iPr S OCH2C(Me)2CH20 4-C1 4-C1 4-Cl iPr S OCH2C(Me)2CH20 4-Br 4-C1 4-Cl iPr S OCH2C~Me)2CH20 4-OCF3 4-C1 4-Cl iPr S OCH2C(Me)2CH20 4-OCF2H 4-C1 4-Cl iPr S OCH2C(Me)2CH20 4-CF3 4-F 4-Cl iPr S OCH2C(Me)2CH20 . 4-Br 4-F 4-Cl iPr S OCH2C(Me)2CH20 . 4-OCF3 4-F 4-Cl iPr S OCH2C(Me)2CH20 - 4-CF3 4-OCF2H 4-Cl iPr S OCH2C(Me)2CH20 :~ 4-oCF3 2 iPr S OCH2C(Me)2CH20 : 15 4-CF3 4-Cl 4-CN iPr S OCH2C(Me)2CH20 4-OCF3 4-C1 4-CN iPr S OCH C(Me) CH O
v 4-CF3 4-F 4-CN iPr S OCH2C(Me)2CH20 4-OCF3. 4-F 4-CN iPr S OCH2C(Me)2CH20 -CF3 4-C1 4-CO2Me iPr S OCH2C(Me)2CH20 . . 2 D 4-CE3 4-Cl H tBu S OiPr OiPr 4-CF3 4-F H tBu S OiPr OiPr 4-CF3 4-OCF2H H tBu S OCH2CH2CH20 4-OCF3 4-OCF2H H tBu S OCH2CH2CH20 4-CF3 4-Br H tBu S CH2cH2cH2 4-CF3 4-C1 4-Cl tBu S OCH2CH20 , 4-~r 4-C1 4-Cl t8u S OCB2CH20 .~, 4-OCF3 4-C1 4-Cl tBu S CH2c~2 . 4-CF3 4-F 4-Cl Me S OEt OEt 4-OCF3 4-F 4-Cl Me S OEt OEt ~ .
4-CF3 4-OCF2H 4-Cl Me S OEt OEt 4-C1 4-OCF2H 4-Cl Me S OEt OEt .. 4-CF3 4-F 4-CN tBu O OEt OEt ~' 4-OCF3 4-F 4-CN tBu O OEt OEt 4-CF3 4-C1 2 2 ( )2CH2 ,', `
., .
"
: : ~ : .
.~
2~ 013~
~able 19 5 .
.
R2~R3 ; N ~
}R1 ~ -P -YlR~l : R8 Rl o : ' .
.
.~ Rl R2 R3 R8 yl Rlo ylR
v ; 4-CF3 4-Cl H iPr O Et OEt ,. 4-OCF3 4-Cl N iPr O Et OEt : 25 4-CF3 4-F N iPr O Et OEt ; 4-OCF3 4-F H iPr O Et OEt :' 4-CF3 4-OCF2H H iPr O Et OEt '' 4-OCF 4-OCF H H iPr O Et OEt . 3 2 -; 4-CF3 4-Br H iPr O Et OEt . .
~ ~ 4-CF3 4-C1 4-Cl iPr O Et OEt '~ 4-C1 4-C1 4-Cl iPr O Et OEt 4-i3r 4-C1 4-Cl iPr O Et OEt ~' 4-OCF3 4-C1 4-Cl iPr O Et OEt ~- 4-OCF2H 4-C1 4-Cl iPr O Et OEt 4-CF3 4-F 4-Cl iPr O Et OEt 4-C1 4-F 4-Cl iPr O Et OEt 4-Er 4-F 4-CI iPr O Et OEt .., , ' ,:
Z~C~C~130 R1 R2 R3 ~ R8 yl Rlo ylR
i-oCF3 4-F 4-Cl iPr O Et OEt 4-CF3 4-OCF2H 4-Cl iPr O Et OEt 4-OCF3 9-OCF2H 4-Cl iPr O Et OEt 4-CF3 4-C1 4-CN iPr O Et OEt 4-OCF3 4-C1 4-CN iPr O Et OEt 4-C~3 4-F 4-CN iPr O Et OEt 4-OCF3 4-r 4-CN iPr O St OEt 4-C~3 4-C1 4-CO2MelPr O Et OEt 4-CF3 4-Cl H iPr O Et OiPr 4-OCF3 4-Cl H iPr O Et OiPr 4-CF3 4-F H iPr O Et OiPr 4-OCF3 4-F H iPr O Et OiPr 4-CF3 4-OCF2H H iPr O Et OiPr 4-OCF3 4-OCF2H ~ iPr O Et OPh : .
4-OCF2H 4-OCF2H H iPr O Et OPh 3,4-CH2C(Me)2O 4-OCF2H H iPr O Et OPh 4-CF3 4-Br H iPr O Et OPh 4-CF3 4-C1 4-Cl iPr O Et OPh 4-C1 4-C1 4-Cl iPr O Et OPh 4-Br 4-C1 4-Cl lPr O Et OPh 4-OCF3 4-C1 4-Cl iPr O Et OPh 4-OC~2H 4-C1 4-Cl iPr O Et OPh 4-CF3 4-F 4-CN tBu O Et OEt 4-OCF3 4-F 4-CN tBu O Et OEt 4-CF3 4-C1 4-CO2MetBu O Et OEt 4-CF 4-Cl H tBu O Et OiPr 4-OCF3 4-Cl H tBu O Et OiPr 4-CF3 4-F H tBu O Et OiPr 4-OCF3 4-F H tHu O Et OiPr q-cF3 4-OCF2H H tBu O Et OiPr 4-OCF3 4-OCF2H N Ph O Et OEt '.
. ,.
':~
,!
Z~ 3~
.~ .
. R2 R3 R8 yl Rlo YlR
4-CF3 9-F H iPr S Et OEt 4-OCF3 4-F H iPr S Ph OEt 4-CF 4-OCF2H 4-Cl tBu S Et OEt 4-OC~3 4-OCF2H 4-Cl tEu S Ph OEt . 4-CF3 9-F 4-CN iPr S iPr OiPr . 10 4-OCF3 4-F 4-CN iPr S nPr OEt 4-CF3 4-C1 4-CO2Me tBu S Me OEt . ,.
,~ 15 ::
.' . .
!i ''~ ,, .``~
' 25 .``' ,' ', -.. . .
.,, j . : .
.` 30 ~ ` , .
., .
~ 35 ~ .
-,, ..-..
2~QQ13~) .
:~ ~able 2~
.' ~, " .
R~
~ ~ R1 S
."
..
R1 R2 _ 3 Rg :-, 4-CF3 4-Cl H CF
~ 4-CF3 4-F 3 '~! 25 4-CF34-OCF2H H CF3 " 4 CF 4-Br H CF3 ,i. 4-CF3 4-Cl 4-Cl 3 4-Cl 4-Cl 4-Cl CF3 .. 30 4-Cl 4-Cl 3 : 4-OCF3 4-C1 4-Cl 3 4-OCF2H 4-Cl 4-Cl 3 ~: .
' 3,4-CH2C(Me)2O ~-Cl 4-Cl 3 -:: 4-CF3 4-F 4-ClCF3 3 4-OCF2H 4-Cl 3 4-CF 4-Cl 4-CN 3 ." .
.,~ . .
.
, ~ . .
3~
. . .
Rl R2 R3 R9 4-CF3 4-C1 4-C02Me CF3 4-CF3 4-Cl H O-~ecBu 4-CF3 4-F ' H 0-6ecBu 4-CF 4-OCF2H H 0-6ecBu 4-C1 4-OCF2H H O-~ecBu ;~ 4-OCF3 4-OCF2H H O-secBu '~
:~ 4-CF3 4-Br H 0-6ecBu 4-CF3 4-C1 4-C1 0-8ecBu 4-C1 4-C1 4-C1 O-secBu : 15 4-Br 4-C1 4-C1 O-secBu 4-OCF3 4-C1 4-C1 0-8ecBu ~: 4-CF3 4-F 4-C1 0-6ecBu 4-C1 4-F 4-C1 0-6ecBu 4-OCF3 4-F 4-C1 0-6ecBu .` 20 4-CF3 4-OCF2H 4-C1 O-secBu ',',! 4-OCF3 4-OCF2H 4-C1 O-secBu 4-CF3 4-C1 4-CN O-secBu . 4-CF3 4-F 4-CN 0-6ecBu . 4-CF3 4-C1 4-C02Me 0-6ecBu , 25 4-CF3 4-Cl H O-n-Bu . 4-CF3 4-F H O-n-Bu ~` 4-CF3 4-OCF2H H O-n-Bu 4-C1 4-OCF2H H O-n-Bu 4-Hr 4-OCF2B H O-n-Bu : -4~OCF3 4-OCF2H H O-n-Bu `~
4-OCF2H 4-OCF2H H O-n-Bu ~ .
3~4-CH2C~Me)20 4-OCF2H . H O-n-Bu , 4-CF3 4-Br H O-n-Bu ~ ,~
'~ 4-CF3 4-C1 4-Cl O-n-Bu , 4-C1 4-C1 4-Cl O-n-Bu . 4-OCF3 4-C1 4-Cl O-n-Bu :
4-CF3 4-F 4-Cl O-n-hexyl .; ~
:~ :
- . :
', : :
2~100~30 Rl R2 R3 Rg - 5 4-Cl 4-F 4-ClO-n-he~yl 4-OCF3 4-F 4-ClO-n-he~yl 4-CF3 4-OCF2H 4-ClO-n-he~yl 4-CF3 4-C1 4-CNO-D-he~yl 4-CF3 4-F 4-CNO-n-he~yl 4-CF3 4-C1 4-CO2Me O-n-he~yl : 4-CF3 4-OCF2H 2 3 -CF3 4-Br HOCH2CC13 :`
:~ 4-OCF3 4-C1 4-ClOCH2CC13 " 20 4-CF3 4-F 4-ClOCH2CH2OEt 4-CF3 4-OCF2H 4-ClOCH2CH2OEt . 4-CF3 4-C1 4-CNoCH2CH2OEt ~:
4-CF3 4-F 4-CNOCH2CH2OEt :~" 25 4-CF3 4-C1 4-CO2Me OCH2CHzOEt ~;
.
.
.. 30 :,' ~'.' , ~ .
:,. .
,' ' .
. ,. ~ .
:'`'` ' .' .
Z~?00:130 :
Table 21 :
~. .
.~ 10 R2~R3 N ~ ~:
~ ~ R1 . I , .
S -p-ORlo . OR1 ~
:.i . ,. ' .
, ~ -, 20 .~ l R2 R3 Rlo Rll : .
-~ 4-CF3 4-Cl H Et Et j ~' 4-CF3 4-F H Et Et 4-CF3 4-OCF2H H Et Et .
4-CF3 4-Br H Et Et "` .
4-CF3 4-Cl 4-Cl Et Et ,,~ 4-Cl 4-Cl 4-Cl Et Et '~1 4-Br 4-Cl 4-Cl Et Et ~! 4-OCF3 4-Cl 4-Cl Et Et 4-OCF H 4-Cl 4-Cl Et Et 3,4-CH2C~Me)2O 4-C1 4-Cl Et Et '~. 4-CF3 4-F 4-Cl Et Et 4-Cl 4-F 4-Cl Et St 4-Br 4-F 4-Cl Et Et , .', :
.
'.''. '~ , ':
.. ~ .
. . .
7 . i' ~ ~, 2~ 01.. ~0 Rl R2 R3 Rl~ Rll 4--OCF3 4-F 4-Cl ' Et Et 4-OCF2H 4-F 4-Cl Et Et 3,4-CH2C(Me)20 4-F 4-Cl Et Et 4-CF3 4-OCF2H 4-Cl Et Et 4-CF3 4-C1 4-CN Et Et 4-CF3 4-F 4-CN Et Et 4-CF3 4-C1 4-CO2Me Et Et 4-CF 4-Cl H -CH2CH2- .
4-CF 4-9r H -CH2CH2-4-CF3 4-C1 4-Cl-CH2CH2- , 4-C1 4-C1 4-Cl-CH2CH2-4-OCF3 4-C1 4-Cl-CH2CH2-4-CF 4-F 4-Cl-CH2CH2CH2-4-C1 4-F 4-Cl-CH2CH2CH2-4-OCF3 4-F 4-Cl-CH2CH2CH2-q-CF3 4-OCF2H 4-Cl-CH2CH2CH2-4-OCF3 4-OCF2H 4-Cl-CH2CH2CH2-~-CF3 4-F 4-CN2 2 2 3 4-C1 4-CO2Me2 2 2 4-CF3 4-Cl H-CH2C(Me)2CH2-4 CF 4-F 2 ( )2 2 4-CF3 4-OCF2H H-CH2C(Me)2CH2-4-CF3 4-~r ~-CH2C~Me)2CH2-4-CF3 4-C1 4-Cl-CH2C~Me)2CH2-4-C1 4-C1 4-Cl-CH2C~Me)2CH2-4-~r 4-C1 4-Cl-CH2C~Me)2CH2-.
4-OCF3 4-C1 4-Cl-CN2C~Me)2cH2- . ~.
.
,: - .
., ' '.
, . : : - : . . . : : :
Z~)00~30 Rl R2 R3 Rlo R
4-OCF H 4-C1 4-Cl -CH2C(Me)2CH2-3,4-CH2C(Me~2O 4-C1 4-Cl -CH2C(Me~2CH2-4-CF3 4-F 4-Cl. Ph Ph 4-CF 4-OCF2H 4-ClPh Ph 4-CF 4-C1 4-CNPh Ph 0 4-CF3 4-F4-CN Ph Ph 4-CF3 4-C1 4-CO2Me Ph Ph , ...
~
. .
.
., ' ~' ~,`.,.. ' "
, ., .
,' ~, 30 . ., ''' :
. '. ,.
., . .`: - .
~ 35 .' . :
,. . .
.. . .
~\
Zl~C~0~310 Table 22 :~ 5 J~3 B
Re : 15 .,., R-2 ~ .
:`
, :,, .: .
Rl R2 R3 R8R12 ~ 4-CF3 4-Cl H DBunBu :; 4-C1 4-Cl H nBunBu . 4-OCF3 4-Cl H nBuDBu -CF3 4-F H nBuDBu :~-` 5 4-CF3 4-OCF2H H nBunBu -~- 4-OCF3 4-OCF2H H nBunBu .
4-CF3 4-Br H nBunBu . 4-CF3 4-C1 4-Cl nBunBu `~ 4-C1 4-C1 4-Cl ~BuD8U
:~ 30 4-Br 4-C1 4-Cl nBu nBu 4-OCF3 4-C1 4-Cl DBu~Bu ~` 4 CF 4-F 4-C1 22CH2CH2CH2_ ..
4-CF3 4-OCF2H 4-C12CH2~H2C~zCH2_ 4-CF3 4-Cl 4-CN-CH2CH2CH2CH2CH2_ ~ 35 4-CF3 4-F 4-CN-CH2CH2CH2CH2C~2-' ' :
'~ ;'............................................................ ',',' - \
4-CF 4-C1 4-CO2Me -CH2CH2CH2CH2CH2-4-CF3 4-Cl H -CH2CH20CH2CH2- ..
4-OCF3 4-Cl H 2 2 2 2 4-CF 4-F . H -CH2CH20CH2CH2-4-CF3 4-OCF2H H -CH2CH20CH2CH2- ~, 4-OCF3 4-OCF2H H -CH2CH20CH2cH2~
4-CF3 4-Br H -CH2cH2c82cH2-4 C 4-C1 4-Cl -CH2CH20CH2CH2- ..
4-C1 4-C~ 4-Cl -CH2CH20CH2CH2-4-Br 4-Cl 4-Cl -CH2CH20CH2CH2-: 9-OCF3 4-C1 4-Cl -CH2CH20CH2CH2-4-CF 4-F 4-Cl -CH2CHMeOCBMeCH2-4-CF 4-OCF2H 4-Cl -CH2CHMeOCHMeCH2-4-CF3 4-C1 4-CN -CH2CHMeOCHMeCH2- . :
4-CF3 4-F 4-CN -CH2CHMeOCHMeCH2-4-CF3 4-C1 4-CO2Me -CH2CHMeOCHMeCH2-4-CF 4-Cl H Et c ~, 4-CF3 4-F H Et cyclo-C6H
~; 4 CF 4-OCF2H H Et c ". 25 4-CF3 4-Br ~ Et c ~` 4-C1 4-Cl Et c - 4-C1 4-C1 4-Cl Et c .~ 4-Fr 4-C1 4-Cl Et cyClo-c6 . 4-OCF3 4-C1 4-Cl Et c ; 4-CF3 4-F 4-Cl iPr -CH2CH2CO2ET
4-C1 4-F 4-Cl iPr -CH2cH2c2ET
.~ 4-OCF3 4-F 4-Cl iPr -CH2cH2c2ET
3 4-OCF2H 4-Cl iPr -CH2cH2c2ET
4-C1 4-OCF2B 4-Cl iPr -CH2CH2C02ST
4-Br 4-OCF2H 4-Cl iPr -CH2cH2c2~T
.. 35 q-OCF3 2 iPr -CH2CH2CO2ET
,' ' . ~
~ :
.. ...
.'' '"'~'~
.:- : : : , ' ' : . . : : -,, : :''"',''. ',' ' ' '' '."'' ':',' ' ' 2l~0(~`13(;~
Rl R2 R3 R8 R12 4~OCF2H 4-OCF2H 4-Cl lPr -CH2CH2C02ET
3,4-CH2C(Me)2O 4-OCF2H 4-Cl iPr -CH2CH2CO2ET
4-CF3 4-C1 4-CN iPr -CH2CH2CO2ET
4-C1 4-C1 4-CN iPr -CH2CH2CO2ET
4-OCF3 4-C1 4-CN CF3 . 2,4-di-Cl-Ph 4-CF3 4-F 4-CN CF3 2,4-di-Ci-Ph 4-CF 4-C1 2 3 2,4-di-Cl-Ph : 15 .~ .
','', :
~ 20 .
'~, : 25 ~` ''.
. ~ .
:; 30 .~`i ,:
~ 35 :
:
,:, - ~ . - , . -: . : . .: : : :
Z'~ ~0~30 ~j~
Table 23 Rz ~ R3 o~uJ~
S~R10 ','' ' .. ...
~'< ';'' ' , 20 ` Rl R2 R3 R10 .j.` 4-CF3 4-Cl H tBu 4-OC~ 4-Cl H tBu .~ 25 4-CF3 4-F H tBu ~"3 4-CF3 4-OCF2H H tBu ~ 4-OCF3 4-OCF2H H tBu .~: 4-CF3 4-Br H tBu ' 4-CF3 4-C1 4-Cl tBu : 30 4-C1 4-C1 4-Cl tBu ................ 4-Br 4-C1 4-Cl tBu 4-OCF3 4-C1 4-CI tBu " 4-OCF2N 4-C1 4-Cl tFu .'; 4-CF3 4-~ 4-Cl tBu 4-CF3 4-OCF2H 4-Cl tBu . , ,' ., .
' ' Z~ 'Pl3~ ' Rl R2 R3 Rlo _ _ . .
5 i-Cl 4-OCF2H 4-Cl tBu 4-OCF3 4-OCF2H 4-Cl tBu 4-CF3 4-C1 4-CN tBu 4-CF3 4-F 4-CN tBu 4-CF3 4-C1 4-CO2Me tBu ~ 10 4-CF3 4-Cl H sec-Fu .: 4-OCF3 4-Cl H ~ec-Bu 4-CF3 ~-F H cec-Fu .- 4-OCF3 4-F H ~ec-Bu : 4-CF 4-OCF2H H ~ec-Bu 4-C1 4-OCF2H H ~ec-8u 4-OCF3 4-OCF2H H Ph , 4-OCF2H 4-OCF2H H Ph 3,4-CH2C(Me)20 4-OCF2H H Ph 4-CF3 4-Br H Ph 4-CF3 4-C1 4-Cl Ph 4-C1 4-C1 4-Cl Ph 4-Br 4-C1 4-Cl Ph 4-OCF3 4-C1 4-Cl - Ph . 4-OCF2H 4-C1 4-Cl Ph - 25 3,4-C82C(Me)20 4-C1 4-Cl Ph 4-CF3 4-F 4-C1 4-Cl-Ph 4-C1 4-F 4-C1 4-Cl-Ph :; 4-Br 4-F 4-C1 4-Cl-Ph 4-oCF3 4-F 4-C1 4-Cl-Ph 4-OCF2H 4-F 4-C1 4-Cl-Ph 3~4-CH2C~Me~20 4-F 4-C1 4-Cl-Ph ; 4-CF3 4-OCF2H 4-C1 4-Cl-Ph 4-CF3 4-Cl 4-CN 4-Cl-Ph ,. 4-OCF3 4-C1 4-CN 2-Me-4-t-Bu-Ph :
.. , 1, ~' 35 ., .
,.' . ' .
'~ ~
. 170 :
; Rl R2 R3 Rlo 4-CF 4.F 4-CN2-Me-4-t-Bu-Ph ~: 4-OCF3 4-F 4-CN2-Me-4-t-Bu-Ph 4-CF3 4-C1 4-CO2Me2-Me-4-t-Bu-Ph .::
4-CF 4-C1 H2-NO2-Ph 4-OCF3 4-Cl H2-NO2-Ph 4-CF3 4-F H2-NO2-Ph 4-CF3 4-OCF2H H 2-NO2-Ph 4-CF 4-Br H2-NO2-Ph 4-CF3 4-C1 4-C12-N2-Ph 4-Br 4-C1 4-C12-NO2-Ph : 4-OCF3 4-C1 4-C12-NO2-Ph .'. 4-CF3 4-F 4-C12-NO2Ph 4-Cl 4-F 4-C12-NO2Ph q C 4-OCF2H 4-C12-N2Ph 4-OCF3 4-OCF2H 4-C12-NO2Ph 4-CF3 4-C1 4-CN2-NO2Ph 4-OCF3 4-C1 4-CN2-NO2Ph :.` 25 4-CF3 4-F 4-CN2-NO2Ph ~ 4-CF 4-C1 4-CO2Me2-N2Ph ~:
.'', :
... . .
~,. i :.;
:. ' ~5 :~
.. ;
G
2~?0013(:~
Table 24 .
~.
10 ~ 3 fi2 j~
~N
~,Rl ~ .
15 ~ , ." ~,.
: 20 :~. Rl R2 R3 Z
.~` 4-CF3 4-H 4-H CH3 ~- 25 4-CF3 4-H 4-Cl CH3 4-CF3 4-F 4-Cl CH3 . 4-CF3 4-F 4-F CH3 4-CF3 4-C~ 4-Cl CH3 4-C~3 4-Cl 4-F CH3 '~ 4-CF3 4-OCHF2 4-H CH3 4-CF3 4-OCHF2 4-Cl CH3 ~` 4-CF3 4-OCHF2 4-F CH3 ' 35 .
., .
'.~
,j. :
.''. . ~'~.
;.:, . . ... . . . . , , ` ` ~
2;1100~30 172 :.
:: R R2 R3 Z
~. .
4-OCF3 4-H 4-H CH3 ..
4-OCF3 4-R 4-Cl CH3 ~ 4-OCF3 4-F 4-H CH3 .: 10 4-OCF3 4-F 4-Cl CH3 . 4-OCF3 4-F 4-F CH3 .. : 4-OCF3 4-C1 4-Cl CH3 .: 4-OCF3 4-C1 4-F C~3 :~ 15 4-C1 4-H 4-H CH3 :` 4-C1 4-H 4-Cl CH3 . 4-C1 4-H 4-F CH3 .
.~ 4-C~ 4-C1 4-H CH3 :.
4-C1 4-C1 4-Cl CH3 : 20 4-C1 4-C1 4-F CH3 4-C1 4-F 4-Cl CH3 4-C1 4-F 4-F . CH3 " 4-Br 4-H 4-H CH3 4-8r 4-H 4-F CH3 . 4-Br 4-~ 4-Cl CH3 ., 4-Br 4-C1 4-H CH3 . 4-8r 4-C1 4-F CH
4-Er 4-C1 4-Cl CH3 4-Br 4-F 4-H CH3 4-Br 4-F 4-F CH3 4-~3r 4-F 4-Cl CH3 . 4-OCHF2 4-H 4-H C~3 .. 4-OCHF2 4-H 4-F CH3 4-OCHF2 4-H 4-Cl CH3 ;' ~ ~'.
,. ~ . . . - : .: .
0~3Q
. Rl R2 R3 Z
~ .
4-OCHF2 4-F 4-Cl CH3 4-OCHF2 4-Cl 4-H CH3 4-OCHF2 4-C1 4-Cl CH3 4-CF3 4-H 4-Cl CH3CH2 .. 4-CF3 4-F 4-H CH3CHZ
4-CF3 4-F 4-Cl CH3CH2 .
4-CF3 4-C1 4-H C~3CH2 4-CF3 4-C1 4-Cl CH3CH2 . 4-CF3 4-C1 4-F . CH3C~2 4-CF3 4-OCHF2 4-Cl CH3CH2 .. 4-OCF3 4-H 4-H CH3CH2 `. 25 4-OCF3 4-H 4-Cl CH3CH2 .. 4-OCF3 4-H 4-F CH3CH2 ,~ 4-OCF3 4-F 4-H CH3CH2 4-OCF3 4-F 4-Cl CH3CH2 .- 30 4-OCF3 4-C1 4-Cl CH3CH2 4-C~ 4-H 4-H CH3CH2 4-C1 4_~ 4-C1 3CH2 ,` ~
,: . : : ' ':
`, !'''~: "
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~ , , - .-. .:. .:: :,.
;~ ~
Z~-~00130 . .
Rl R2 R3 Z
.
- 4-C1 4-C1 4-Cl CH3CH2 : 4-C1 4-C1 4-F CH3 Q2 4-C1 4-F 4-H CH3CH2 , .` 10 4-C1 4-F 4-Cl CH3CH2 4-C1 4-F 4-F CH3CH2 ~:
4-CF3 4-H 4-Cl C6H5 : 4-CF3 4-F 4-Cl C6H5 : q-CF3 4-F 4-F C6H5 4-CF3 4-C1 4-Cl C6H5 . 20 4-CF3 4-C1 4-F C6H5 ~r~ 4-CF3 4-OCHF2 4-H C6H5 ~. 4-CF3 4-OCHF2 4-Cl C6H5 .'i.' 4-CF3 4-OCHF2 4-F C6H5 ~' 25 4-OCF3 4-H 4-H C6H5 ;~ 4-OCF3 4-H 4-Cl C6H5 ~`, 4-OCF3 4-H 4-F C6H5 .
:' 4-OCF3 4-F 4-H C6H5 ' 4-OCF3 4-F 4-Cl C6H5 .. 4-OCF3 4-F 4-F C6H5 3~ 4-OCF3 4-C1 4-H C6H5 .
.-. 4-OCF3 4-C1 4-Cl C6H5 : 4-OCF3 4-C1 4-F C6H5 4-C1 4-H 4-H C6~5 4-C1 4-H 4-Cl C6H5 ~5 4-C1 4-H 4-F C6H5 , '; ' . . ~
~'', :";
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, :
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`: - : : . .. ~ . . , 2~)C~31~
4-C1 4-F 4-Cl C6H5 4-CF3 4-H 4-Cl C~30 4-CF3 4-F 4-Cl CH30 : 15 4-CF3 4-C1 4-H CH30 4-CF3 4-C1 4-Cl CH30 ~ 4-CF3 4-C1 4-F CH30 `; 4-CF3 4-OCHF24-Cl CH30 : 20 4-CF3 4-OCNF24-F CR30 :. 4-OCF3 4-H 4-H CH30 ., 4-OCF3 4-H 4-Cl CH30 4-OCF3 4-F 4-Cl CH30 .` 4-ocr3 4-F 4-F CH30 :' 4-OCF3 4-C1 4-H CH30 .' 4-OCF3 4-C1 4-Cl CH30 ":` 4-OCF3 4-C1 4-F CH30 ~ 4-C1 4-H 4-Cl CH30 .,1 4-C1 4-H 9-F CH30 4-C1 4-C1 4-Cl CH30 ~ . ~
:. :
,:
:-,. , : :
Z~00130 R R2 R3 _ _ _ _ 4-C1 4-F 4-Cl CH30 .
4-CF3 4-H 4-Cl H
4-CF3 4-F 4-Cl H
4-CF3 4-C1 4-Cl H
4-CF3 4-OCHF2 4-H H ~.
4-C~3 4-OCHF2 4-Cl H
4-CF3 4-OCHF2 4-F H .
q-OCF3 4-H 4-H H
4-OCF3 9-H 4-Cl H
4-OCF3 4-F 4-Cl H . :.
4-OCF3 4-C1 4-H H ~.
4-OCF3 4-C1 4-Cl H
4-CI 4-H 4-H .H
4-C1 4-H 4-Cl H
4-C1 4-C1 4-Cl H
., .
:, :
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2~(j0~.3~
Rl R2 R3 Z
: 5 4-C1 4-F 4-Cl H
-CF3 4-C1 4-Cl BrCH2 10 4-CF3 4-C1 4-Cl ClCH2 9-CF3 4-C1 4-Cl CF3 4-CF3 4-C1 4-Cl benzyl 4-CF3 4-C1 4-Cl CH3CH2CH2 4-CF3 4-C1 4-Cl CH3(CH2)3 lS 4-CF3 4-C1 4-Cl CH3(CH2)4 4-CF3 4-C1 4-Cl CH3(CH2)5 4-CF3 4-C1 4-Cl CH3(CH2)6 4-CF3 4-C1 4-Cl CH3(CH2)7 .
: 4-CF3 4-C1 4-Cl CH3(CH2)9 20 4-CF3 4-C1 4-Cl CH3(CH2)10 4-CF3 4-C1 4-Cl C13C
4-CF3 4-C1 4-Cl i-Pr 4-CF3 4-Cl 4-Cl t-Bu 4-CF3 4-C1 4-Cl MeO2C
-CF3 4-C1 4-Cl EtO2C
4-CF3 4-C1 4-C1 2-Cl-phenyl 4-CF3 4-C1 4-C1 3-Cl-pbenyl 4-CF3 4-C1 4-C1 4-Cl-phenyl , 4-CF3 4-C1 4-Cl CH3CH20 30 4-CF3 4-C1 4-Cl CH3(CH2~20 ` 4-CF3 4-C1 4-Cl CH3(CH2)40 4-CF3 4-C~ 4-Cl CH3(CH2)60 4-CF3 4-C1 4-Cl CH3(CH2)Bo 4-CF3 4-C1 4-Cl CH3(CH2)100 35 4-CF3 4-C1 4-Cl phenyl-0 4-CF3 4-C1 4-C1 4-Cl-pbenyl-0 '~ .
2i~0130 Rl R2 R3 Z
5 .
4-CF3 4-C1 4-Cl benzyl-O
4-C1 4-C1 4-Cl ClCH2 4-C1 4-C1 4-Cl CF3 4-CI 4-C1 4-Cl benzyl 10 4-C1 4-C1 4-Cl CH3~CH2)3 4-C1 4-C1 4-Cl CH32C
4-C1 4-C1 4-Cl CH3CH2O
.~
: 1 5 .
i i'-' 20 `' :,.
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Table `' ' '', ' Rz ~ ~ R3 . N
S~N,L~R
R8 . !
.
. R2 R3 R8 Rg .. 4-CF3 4-Cl H Me O-nBu 4-OCF3 4-Cl H Me O-n9u .~ - 2S 4-CF3 4-F H Me O-nBu ,~. 4-OCF3 4-F H Me O-nBu -CF3 4-OCF2H H Me O-nBu 4-CF3 4-8r H Me O-nBu . 4-CF3 4-Cl 4-Cl Me O-nBu 30 4-Cl 4-Cl 4-Cl Me O-nBu 4-Br 4-Cl 9-Cl Me O-nBu ,. 4-OCF3 4-Cl 4-Cl Me O-nBu 4-CF3 4-F 4-Cl Me O-nBu 4-CF 4-OCF2H 4-Cl Me O-nBu ,` 4-CF3 4-Cl 4-CN Me O-nBu ; 35 .;
:' Z00013(~
Rl R2 R3 R8 Rg :
4-CF3 4-F 4-CN Me O-nBu 4-CF 4-C1 4-C02Me Me O-DEU
4-CF3 4-Cl H Me O-~-he~yl 4-CF3 4-F H Me O-n-hexyl 4-CF3 4-OCF2H N Me O-n-octyl 4-CF3 4-Br 8 Me O-D-decyl 4-CF3 4-C1 4-Cl Me O-n-dodecyl 4-C1 4-C1 4-Cl Me O-n-dodecyl 4-Br 4-C1 4-Cl Me O-n-dodecyl 4-OCF3 4-C1 4-Cl Me O-n-dodecyl 4-CF3 4-F 4-Cl Me O-sec-Bu 4-C1 4-F 4-Cl Me O-sec-Fu 4-Br 4-F 4-Cl Me O-sec-Bu 4-OCF3 4-F 4-Cl Me O-sec-Bu - 4-CF3 4-OCF2N 4-Cl Me 0-6ec-Bu : q-CF3 4-C1 4-CN Me O-iPr .
4-C~3 4-F 4-CN Me OCH2CH20Et `~ 4-C1 4-C02Me Me 2 3 4-CF3 4-Cl H Me F
4-F H Me 2 3 4-OCF2H ~ Me NEtz 4-CF3 4-Br H Me morpholino ,. 4-OCF3 4-Br H Me n-Pr 4-CF3 4-C1 4-Cl Me sec-Bu 4-~r 4-C1 4-Cl Me Ph 4-OCF3 4-C1 4-Cl Me Ph :~ 4-CF3 4-~ 4-Cl Et O-iPr ' 30 4-CF3 4-OCF2H 4-Cl Et O-iPr 4-CF 4-C1 4-CN St OCH2ccl3 i 4-OCF3 4-C1 4-CN Et NEt2 4-CF3 4-F 4-CN Et 2,6-di_~e-~orpholino 4-C1 4-F 4-CN Et 2,6-di-Me-morpholino -CF3 4-C1 4-C02Me Et Ph 4-CF3 4-Cl H iPr OEt 4-CF3 4-F H iPr OEt .
- , . , . - . ~.. - " .-- - . ~ . -- - .. . : :: ~ - : .: : . . : : .. . .
2~Q013() R2 R3 R8 Rg 4-OCF2H H iPr OEt 4-C1 4-OCF2H H iPr OEt 4-Br 4-OCF2H H iPr OEt 4-OCF3 4-OCE2H H iPr OEt 4-OCF2H 4-OCF2H H iPr OEt 3,4-CH2C(Me)20 4-OCF2~ H iPr OEt 4-CF3 4-Br H iPr OEt 9-CF~ 4-C1 4-Cl iPr OEt 4-OCF3 4-C1 4-Cl iPr OEt ~,~ 4-CF3 4-F 4-Cl iPr OEt 4-OCF3 4-F 4-Cl iPr OEt-4-CF 4-OCF2H 4-Cl iPr OEt : 4-OCF3 4-OCF2H 4-Cl iPr OEt . 4-CF3 4-C1 4-CN iPr OEt 4-OCF3 4-C1 4-CN iPr OEt ':~ 20 4-CF3 4-F 4-CN iPr OEt 4-CF3 4-C1 4-CO2Me iPr OEt ., 4-OCF3 4-C1 4-CO2Me iPr OEt ~ 4-CF3 4-OMq 4-Cl iPr OEt i, 4-C1 4-OPh 4-Cl iPr OEt ~ 25 4-Pr 4-SCF2H 4-Cl iPr OEt ,.
4-OCF3 4-No2 4-Cl iPr OEt i 4-OCF2H 4-SMe 4-Cl iPr OEt 3,4-CH2C(Me)20 4-SO2Me 4-Cl iPr OEt 4-CF3 4-CN 4-Cl iPr OEt - 30 4-C1 3-C1 4-Cl iPr OEt 4-Br 3-F 4-Cl iPr OEt ~-OCF3 4-Ne 4-Cl iPr OEt 4-OCF2H 4-0-~llyl 4-Cl iPr OEt 3,4-CH2C(Me)20 4-CF3 4-Cl iPr OEt 4 CF 4-C1 4-CO2Et iPr OEt ; 35 4-C1 4-C1 4-OMe iPr OEt 4-Br 4-C1 4-SCF2CF2H iPr OEt 4-OCF3 4-C1 4-OCF2CF2H iPr OEt Z~00~30 ..
Rl R2 R3 R~ Rg 4-CF 4-C1 4-CF3 iPr OEt : 4-Cl ~-Cl 4-Me iPr OEt 4-Br 4-C1 3-Cl iPr OEt 4-OCF3 4-C1 3-Br iPr OEt 4-OCF2H 4-C1 4-NO2 iPr OEt 4-CF3 4-Cl H iPr O-n-Bu : 10 4-CF3 4-F H iPr O-n-Bu 4-OCF3 4-F ~ iPr OCH2CO2Me 4-CF 4-~CF2H H iPr NMe2 4-OCF3 4-OCF2H H iPr piperidino 3,4-CH2C(Me)20 4-0CF2H H iPr Et 4-CF3 4-Br H iPr Et 4-OCF3 4-Br H CH2Ph OEt 4-CF3 4-Cl 4-CO2Me CH2Ph NME2 . 20 ':~ ' ' ,~ :
~ 25 ', . .
:
', , ' ' .
.
.,. ., : . : ~ :
i ~
21)00~ 3~
:
,... .
~ Table 26 ., .
:
~ )~3 N~
O
: 15 N--S -R9 Ra , 3 -Cl 9 3 4-F H Me 2 4-CF3 4-OCF2H H Me n-hexyl ~ .
4-OCF3 4-OCF2H H Me Ph 4-CF3 4-Br H Me 4-Me-Ph ~ 4-CF3 4-C1 4-Cl Et morpholiDo ;.~ 4-C1 4-C1 4-Cl Et iPr '. 4-Br 4-C1 4-Cl Et n-Bu ::
: 30 4-OCF3 4-C1 4-Cl Et Ph 4-CF 4-F 4-Cl iPr NMe2 4-CF3 2 iPr piperidino 4-C1 4-OCF2H 4-Cl iPr Et :~
4-Br 2 Cl iPr D-Bu . 35 4-OCF3 2 iPr Ph 4-OCF2H 2 Cl iPr 4-Cl-Ph ., '. .
... . .
.' j`'' ' ', ;' ' '' Table 27 Rz ~ ~ R3 N ~
S ~ _p -YlR ;
Re Y R, :
."
R2 R3 R8 yl YlR Y Rll . 4-CF3 4-Cl H tBu S OEt OEt . 4-C1 4-Cl H tBu S OEt OEt 4-Br 4-Cl H tBu S OEt, OEt :~ 25 4-OCF3 4-Cl H tBu S OEt OEt 9-OCF2H 4-Cl H tBu S OEt OEt ;? 3,4-CH2C(Me)2O 4-Cl H tBu S OEt OEt `~ 4-CF3 4-F H tBu S OEt OEt ~ 4-C1 4-F H tBu S OEt OEt t 4-~r 4-F H tBu S OEt OEt 4-OCF 4-F ~ tBu S OCH2C(Me)2CH2O
4-OCF2H 4-F H tBu S OCH2C~Me)2CH2O
3,4-CH2C(Me)2O 4-F H tBu S OCH2C(~e)2CH2O
3 4-OCF2H H tBu S OCH2C(Me)2CH2O
4-C1 4-OCF2H H tBu S OCH2C(Me)2CH2O
4-Br 4-OCF2H H tBu S OCH2C(Me)2CH2O
,, ':
.'' "' .
:-- , . ,,, - ., . - . - , . - - ~ . . .
Zt~ 130 Rl ~2 R3 R8 yl YlR YlR
..
4-OCF3 4-OCF2H H tBu S OCH2C~Me)2CH2O
4-OCF2H 4-OCF2H H tBu S OCH2C(Me)2CH2O
3,4-CH2C(Me)2O 4-OCF2H H tBu S OCH2C(Me)2CH2O
4-CF3 4-Br H tBu S OCH2C(Me)2CH2O
4-C1 4-Br H iPr S OEt OEt : 4-9r 4-Br H iPr S OEt OEt 4-OCF3 4-Br H iPr S OFt OEt 4-OCF2H 4-Br H iPr S OEt OEt 3~4-cH2c(Me)2o 4-Br H iPr S OEt OEt 4-CF3 4-C1 4-CliPr S OEt OEt 4-C1 4-C1 4-CliPr S OEt OEt 4-8r 4-C1 4-CliPr S OEt OEt ..
4-OCF3 4-C1 4-CliPr S OEt OEt :
: .~
4-OCF2H 4-C1 4-CliPr S OEt OEt 3,4-CH2CtMe)2O 4-Cl4-Cl . iPr S OEt OEt -CF3 4-F 4-CliPr S OCH2C(Me)2CH2O ' -Cl 4-F 4-CliPr S OCH2C(Me)2cH2O :
4-Br 4-F 4-CliPr S OCH2C(Me)2CH2O
4-OCF3 4-F 4-CliPr S OCH2C(Me)2CH2O
` 25 4-OCF2H 4-F 4-CliPr S OCH2C(Me)2CH2O
3~4-cH2c(Me)2o 4-F 4-Cl iPr S OCH2C~Me)2CH2O
.~-CF3 2 tBu S OiPr OiPr . 4-C1 4-OCF2H 4-CltBu S OiPr OiPr 4-Br 4-OCF2H 4-CltBu S OiPr OiPr ` 30 3 2 tBu S OiPr OiPr .. 4-OCP2H 2 tBu S OiPr OiPr , .
3'4-CH2C(Me)2O 4-OCF2H 4-Cl tBu S OiPr OiPr q CF3 4-C1 4-CN tBu SOCH2cH2cH2O , 4-C1 4-C1 4-CN tBu 5CHzcH2cH2 4-Br 4-C1 4-CN tBu 2 2 2 . :
4-OCF3 . 4-C1 4-CN tBu SCH2cH2cH2 ,~
, '.
.
.
21~ ~:30~30 : ~1 R2 R3 R8 yl YlR YlR
4-OCF2H 4-C1 4-CN tBu 2 2 2 3~-c~2c(Me)2o 4-C1 4-CN tBuS CH2cH2 4-CF3 4-F 4-CN tBu 2 2 4-C1 4-F 4-CN tBu SCH2cH2 4-Br 4-F 4-CN t8u 2 2 4-OCF3 4-F 4-CN Me SOEt OEt 4-OCF2H 4-F 4-CN Me SOEt OEt 3,4-CH2C(Me)2O 4-F 4-CN Me SOEt OEt ;~ 4-Br 4-C1 4-CO2Me tBu O OEt OEt : 15 4-OCF3 4-C1 4-COzMe tBuO OEt OEt 4-OCF2H 4-C1 4-CO2Me t9u O OCH2C(Me)2CH2O
3,4-CH2C(Me)2O 4-C1 4-CO2Me tBu O OCH2C(Me)2CH2O
.
., ' ~.
. . .
, .
~. 25 .' ' .
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20(~0:13~
~ble 28 5. ' , .
R2 ~ ~ 3 N ~ :
~ ~ Rl .
.~ I y1 N-P -Y1R,1 R~ Rlo :
. ':
': .
; 20 ~,'!, Rl R2 R3 R8 yl R1o Y R
!` i ' , .
; 3 4-Cl N iPr O Et OEt 4-C1 4-Cl H iPr O Et OEt 4-OCF3 4-Cl H iPr O Et OEt - . 25 4-CF3 4-F H iPr O Et O-iPr 4-OCF 4-F H iPr O Et O-iPr 4-CF3 4-OCF2H H iPr O Et O-iPr ~ 4-OCF3 4-OCF2H H iPr O Et OPh .
::. 30 3 4-Br H iPr O Et OPh t' 4-CF3 4-C1 4-Cl iPr O Ph OEt ` 4-C1 4-C1 4-Cl iPr O Ph OEt ~.~ 4-Br 4-C1 4-Cl iPr O Ph OEt ~:~
'. 4-OCF~ 4-C1 4-Cl iPr O Ph OEt :
4-CF3 4-F 4-Cl tBu O Et OEt 4-OCF3 4-F 4-CI tBu o E~ OEt .` ' ~ .
, ''':
;' ~
,, ':,:
,.~ . .:
Rl R2 R3 R8 yl R1o ylRll C 2 4 Cl tBu O Et O-~Pr 4-OCF3 2 Cl tBu O Et O-iPr 4-CF3 4-C1 4-~N Ph O - Et OEt 4-OCF3 4-C1 4-CN Ph O Et OEt 4-CF3 4-F 4-CN iPr S Ph O-iPr 4-OCF3 4-F 4-CN tBu S Et OEt ; .
;
'.,.
.' ~
.,; .
:~ , - : : . . . : . . :, . : , 2~Q0130 Table 29 : 5 :
0 R2 ~ ~ 3 . ~N
.- ~,~
S~
. 15 ::
R~ ~
. ~:
~ 20 Rl R2 R3 R9 .~ .
.. g-cF3 4-Cl H CF3 `' 3 4-F 3 , 4-OCF3 4-F H O-sec-Bu ,(~ - 25 4-CF3 4-OCF2H H 0-6ec-Bu ~, 4-Br 4-OCF2H H O-~ee-Bu 4-OCF3 4-OCF2H H O-~ec-Bu .:
4-CF3 4-Br B O-n-Bu ;
4 C 4-C1 4-Cl O-n-Bu 30 4-C1 4-C1 4-Cl O-n-Bu . :
.~ 4-Br 4-C1 4-Cl O-n-Bu . . .
~ 4-OCF3 4-C1 4-C1 O-n-Bu i 4-CF3 4-F 4-Cl O-n-heryl : 4 CF3 4-OCF2H 4-Cl O-n-he~yl 4-OCF3 4-OCF2H 4-Cl O-n-he~yl ':
. . .
, ,. '~
2~U0:1~30 Rl R2 R3 Rg j-CF 4-C1 4-CN 2 3 4-OCF3 4-C1 4_CN 2 3 4_CF3 4-C1 ~ 4-CO2Me OCH2CH20Et ', 10 .
.
:
::
''' '-.
20~0130 Tablç 30 :,.
~ ~ R3 I O
~ -'OR10 ORl 1 ., ~ :' .
:.
Rl R2 R3 R10 R~
4-CF3 4-Cl H Et Et 4-CF3 4-F H Et Et 4-CF3 4-OCF2H H Et Et 4-CF3 4-Br 2 2 4-CF3 4-C1 4-Cl -CH2CH2-3D 4-C1 4-C1 4-Cl -CH2CH2-4-ocr3 4-C1 4-Cl -CH2CH2-4-CF3 4-F 4-Cl -CH2CH2CH2-4-CF3 4-OCF2U 4-C1 2CH2CH2 .
4-OCF3 4-OCF2H 4-CI -CN2C(Me)2CH2 : . . ~ ., . :: , , . . , ~ . , , . . :
.
.: : . , , 2~:~(70 ~30 ~ - R2 R3 R10 Rll 4-CF3 4-C1 4-CN -CH2C(Me)2CH2-4-OCF3 4-C1 4-CN -CH2C(Me)2CH2-4-CF3 4-F 4-CN Ph Ph 4-CF 4-Cl 4-CO2Me Ph Ph ~ .',.
; 20 ~ ~
.:
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~ 35 ;. ' :
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~ 193 . ~ -:, .
~ble 31 : 5 ~\
R~
.~ S
~N--Rp R~ 2 -:
. ~ ~';.
~,' Rl R2 R3 R8 R12 ~; 4-C~ 4-Cl H nBu nBu ,~ 4-CF3 4-F H nBu nBu . 4-CF3 4-OCF2H H nBu nBu ~, - 25 4-OCF3 4-OCF2H H 2 2 2 2 2 :.
; 4-CF3 4-Br 2 2 2 2 2 -~ 4-CF3 4-C1 4-Cl -CH2CH20CH2CH2_ :;.: 4-C1 4-C1 4-Cl -CH2CH20CH2CN2_ ~ 4-OCF3 4-C1 4-Cl -CH2CH20CH2CH2_ ."~ 30 q C 3 4-F 4-Cl -CH2CH(Me)OCH(Me)CH -4-OCF3 4-F 4-Cl -CH2CH~Me)OCH(Me)CH -:, 4-CF3 4-OCF2H 4-Cl Et ~yclo-C6H
4-OCF3 2 Et c ., 4-CF3 4-C1 4-CN Et ~YCl-~6N
35 4 CF3 4-F 4-CN iPr 2 2 2 4-CF3 4-C14-CO2Me CF3 2,4-dl-Cl_Ph ... ... .
~' ' ''.
' ~ .
2C~00:130 . . .
l~ble 32 ~ N ~ R3 . . I ~
}R
.: 15 S
.. .
., ~.
.'.',`
~1 R2 R3 R10 ~ .
4-CF3 4-Cl H tBu i 4-CF3 4-F H tBu !., 25 4-CF3 4-OCF2H H cec-Bu 4-OCF3 4-OCF2H H sec-Bu ~;. 4-CF3 4-Br H cec-Bu ~ 4-CF3 4-C1 4-Cl Ph '. 4-C1 4-C~ 4-Cl Ph .;
~ 4-OCF 4-C1 4-Cl Ph 4-CF3 4-F 4-C1 4-Cl-Ph 4-C1 4-F 4-C1 4-Cl-Ph ~: -s 4-OCF3 4-F 4-C1 4-Cl-Ph ~. 4-CF3 4-OCF2H 4-C1 4-Cl-Ph "` 4 OC 4-OCF2H 4-C1 2-~e-4-t-~u-Ph ~
.. , : .
.,' , .
! ~
.
. . ~ .
~0(30~3~ ~
Rl R2 ~3 Rlo 5 4 CF 4-C1 4-CN 2-Me-4-t-8u-Ph 4-CF3 4-C1 4-CO2Me 2-NO2-Ph ~, .: 15 .~, .
.:
,; 20 ~, .
... . .
',~
.~ :
,.
. -.~ 30 ~ .
~ .
.
,, .
' ' :':
2~013~) Formul~i~n and Use The compounds of this invention will generally be used in formulation with a carrier comprising a liquid or solid diluent or an organic solvent.
Useful formulations of thP compounds of this invention are prep~red in conventional ways. They include dusts, baits, traps, granules, pellets, solutions, suspensions, emulsions, wettable powders, emulsifiable concentrates, dry flowables and the like. Many of thes can be applied directly.
Sprayable formulations can be extended in suitable media and used at spray volumes of from about one to several hundred liters per hectare. High strength compositions are primarily used as intermediates for further formulation. The formulations, broadly, contain about 1% to 99~ solid or liquid diluent(s).
More specifically, they will contain these 20 ingredients in the following approximate proportions: -' .
Percent by Weiaht Active Inaredient Diluent(s~ ~F~actant(s~
25 Wettable Powders 25-90 0-74 0-10 Oil Suspensions, 1-50 40-95 0-35 ` Emulsions, Solutions (including Emulsifi-able Concentrates) Dusts 1-25 70-99 0-5 - 30 l!?
Granules, Baits 0.01-955-99 0-15 ~nd Pellets High Strength 90-99 0-10 0-2 Compositions Lower or higher levels of active ingredient can, of course, be present depending on the intended .
. .
-: - ~- ~ . , , . ... : ,, , . . i ; ~ -: : : ' ' 2000~30 use and the physical properties of the compound.
Higher ratios of surfactant to active ingredient are sometimes desirable, and are achieved by incorporation into the formulation or by tank mixing.
Typical solid diluents are described in Watkins, et al., "Handbook of Insecticide Dust Diluents and Carriers," 2nd Ed., Dorland Books, Caldwell, New Jersey. The more absorptive diluents are preferred for wettable powders and the denser ones for dusts. Typical liquid diluents and solvents are described in Marsden, ~Solvents Guide,~ 2nd Ed., ; Interscience, New York, 1950. Solubility under 0.1%
is preferred for suspension concentrates; solution concentrates are preferably ~table against phase separation at 0C. "~cCurcheon's Detergents and Emulsifiers Annual," Allured Publ. Corp., Ridgewood, New Jersey, as well as Sisely and Wood, "Encyclopedia of Surface Active Agents," Chemical Publ. Co., Inc., New York, 1964, list surfactants and recommended uses.
All formulations can contain minor amounts of addi-tives to reduce foam, caking, corrosion, microbiologi-cal growth, etc. Preferably, ingredients should be approved by the U.S. Environmental Protection Agency for the use intended.
The methods of making such compositions are well known. Solutions are prepared by simply mixing the ingredients. Fine solid compositions are made by blending and, usually, griding as in a hammer or fluid energy mill. Suspensions are prepared by wet-milling (see, for example, U.S. 3,060,084). Granules and pellets can be made by spraying the active material upon preformed granular carriers or by agglomeration techniques. See Browning, "Aqglomeration,~ Chemical , . ' :
- ' -~ ' , . ' .''' .. :...... : ' ~, 19~ -Enaineerinq, December 4, 1967, pages 147 and follow-ing, and ~Perry's Chemical Engineer's Handbook,~ 4th Ea., McGraw-Hill, New York, 1963, pages 8 to 59 and ollowing.
Many of the compounds of the invention are most efficacious when applied in the form of an emul-sifiable concentrate mi~ed with a spray oil or spray oil concentrate. Although any oil can be used as a spray oil, spray oils usually have these character-istics: they are not phytotoxic to the crop sprayed, and they have appropriate viscosity. Petroleum based oils are commonly used for spraying. In some areas, crop oils are preferred such as the following:
~ommon Crop_Oils Us~d as SP~Y Oils Corn Oil Linseed Oil Cottonseed Oil Soybean Oil ` 20 Coconut Oil Sunflower Oil Rapeseed Oil Olive Oil Peanut Oil Palm Oil ~afflower Oil Sesame Oil ~ ;
Mustardseed Oil Castor Oil The following oils also meet the criteria for a spray oil: mineral, fish and cod liver oil.
Spray oil concentrates comprise a spray oil together with one or more additional ingredients such as emulsifiers and wetting agents. A number of useful spray oil and spray oil concentrates can be found in ~A Guide to Agricultural Spray Adjuvants Used in the United States" by Thomson, Thomson Publications, California, 1986.
E~amples of useful arthropodicidal formulations of compounds of the present invention are as follows.
` -, .
. .- .
20(~0~30 Example A
Emulsifiable Concentrate 5 methyl 4-[3-(4-chlorophenyl)-1-[[(ethoxycarbonyl)(l- ;
methylethyl)amino]thio]-N-t4-(trifluoromethyl)phenyl]-amino]carbonyl]-~,5-di-hydro-lH-pyrazo1-4-yl]benzoate.
20%
blend of oil soluble sulfonates and lo polyoxyethylene ethers 10%
isophorone 70%
The ingredients are combined and stirred with gentle warming to speed solution. A fine screen -filter is included in packaging operation to insure the substantial absence of extraneous undissolved ; material in the product.
.~ .
Example B
Wetta~l~ Po~ E
methyl 4-[3-(4-chlorophenyl)-1-[~(ethosycarbonyl)(l-. methylethyl)amino]thio]-N-[4-(trifluoromethyl)phenyl]-amino]carbonyl]-4,5-di-hydro-lH-pyrazol-4-yl]benzoate.
30%
- 25 sodium alkylnaphthalenesulfonate2%
sodium ligninsulfonate 2%
. synthetic amorphous silica 3%
kaolinite 63%
The active ingredient is mixed with the inert materials in a blender. After grindin~ in a hammer-mill, the material is reblended and sifted throu~h a ` 5-mesh screen.
. ~.
E~ample C
nu~
methyl 4-t3-~4-chloroPhenYl)-l-[[(ethoxYcarbonyl)(l-methylethyl)amino]thio]-N-t4-~trifluoromethyl)phenyl]-amino~carbonyl]-4,5-di-hydro-lH-pyrazol-4-yl]benzoate.
., ~ .
,, , : ~ ~ , ;...... ~ . .
. . - .
20(~0130 Wettable powder of Example B 10%
pyrophyllite (powder~ 90%
The wettable powder and the pyrophyllite diluent are thoroughly blended and then packeged.
The product is suitable for use as a dust.
Example D
Granule ` methyl 4-[3-(4-chlorophenyl)-1-[[(etho~ycarbonyl)-(l-methylethyl~amino]thio]-N-[4-(trifluoro-methyl)phenyl]amino]carbonyl]-4,5-di-hydro-lH-pyrazol-4-yl]benzoate. 10%
attapulgite granules (low volative matter, 0.71/9/30 mm; U.S.S. No.
25-50 sie~es) 90%
The active ingredient is dissolved in a vola-tile solvent such as acetone and sprayed upon dedusted and pre-warmed attapulgite granules in a double cone blender. The acetone is then driven off by heating.
The granules are then allowed to cool and are packaged.
E~ample E
~,~
` 25 Emulsifiable Concentrate ..
methyl 4-[3-(4-chlorophenyl)-1-[[(ethoxycarb~nyl)~l-methylethyl)amino]thio]-N-[4-(trifluoromethyl)phenyl]-amino]carbonyl]-4,5-di-hydro-lH-pyrazol-4-yl]benzoate.
^ 10%
blend of oil soluble sulfonates and polyo~yethylene ethers 4%
isophorone 86%
The ingredients are combined and stirred with gentle warming to speed solution. A fine screen filter is included in packaging operation to insure the ab-sence of any e~traneous undissolved material in the ~
product. ~i .~ . .
' ' .
, : :
-Z13()0130 Example F
Wettable P~wder s methyl 4-[3-(4-chlorophenyl)-1-[l(etho~ycarbonyl)(l-methylethyl)amino]thio]-N-[4-(trifluoromethyl)phenyl]-amino]carbonyl]-4,5-di-hydro-lH-pyrazol-4-yl]benzoate 80%
sodium alkylnaphthalenesulfonate 2%
sodium ligninsulfonate 2%
synthetic amorphous silica 3%
kaolinite 3%
- The active ingredient is blended with the inert materials in a blender. After grinding in a hammermill, the material is reblended an sifted through a U.S.S. 50-mesh screen and packaged.
.~ .
E~ample G
"`~ E~ '' wettable powder of E~ample F 5%
. , .
pyrophyllite (powder) 95%
The wettable powder and the pyrophyllite ; diluent are thoroughly blended and then packaged.
The product is suitable for use as a dust.
Example H
Granule methyl 4-[3-(4-chlorophenyl)-1-[[(ethoxycarbonyl)(l-' methylethyl)amino~thio]-N-[4-(trifluoromethyl)phenyl]-amino]carbonyl]-4,5-di-hydro-lH-pyrazol-4-yllbenzoate.
,` 1~%
attapulgite granules (low volative matter, 0.71/0.30 mm; U.S.S. No. 25-S0 sieves) 90%
The active ingredient is dissolved in a suit-able solvent and sprayed onto dedusted attapulgite granules in a double cone blender. The granules are - warmed to drive off solvent, cooled and packaged.
, , .,,, ; .
2~(~013~
Example I
Granule wettable powder of E~ample F 15%
gypsum 69% !
potassium æulfate 16%
The ingredients are blended in a rotating mixer and water is sprayed on to accomplish granu-lation. When most of the material has reached the desired range of 0.1 to 0.42 mm (U.S.S. No. 18 to 40 sieves), the granules are removed, dried, and screened. Oversize material is crushed to produce additional material in the desired range. These qranules contain 12% active ingredient.
.'. :
~xample J
Solu~ion methyl 4-[3-(4-chlorophenyl)-1-[[(ethoxycarbonyl~
methylethyl)amino]thio]-N-[4-(trifluoromethyl)phenyl]-amino]carbonyl~-4,5-di-hydro-lH-pyrazol-4-yl]benzoate.
'~` 15%
4-butyrolactone 85%
-~ The ingredients are combined and stirred to produce a solution suitable for direct, low volume application.
-~ Examp~e K
Oil Suspension methyl 4-t3-(4-chlorophenyl)-1-[t(etho~ycarbonyl)(l-methylethyl)amino]thio]-N-t4-(trifluoromethyl)phenyl]-amino]carbonyl]-4,5-di~hydro-lH-pyrazol-4-yl]benzoate.
r 2 0 %
sodium alkylnaphthalenesulfonate 4%
sodium ligninsulfonate 4%
low viscosity methyl cellulose 3~ -~
attapulgite 69%
... .
,',, ' :' , ,. . .
. .
Z~OO~L30 The active ingredient is blended with the inert materials in a blender. After grinding in a hàmmermill to produce particles substantially all below 100 microns, the material is reblended and sifted through a U.S.S. 50-mesh screen and packaged.
Example L
10 Aqueous Susp~nsi~n -methyl 4-[3-(4-chlorophenyl)-1-[[(ethoxycarbonyl)-(l-methylethyl)amino~thio]-N-[4-(trifluoromethyl)-phenyl]amino]carbonyl]-4,5-dihydro-lH-pyrazol-4-yl]benzoate. 40%
polyacrylic acid thickener 0.3%
dodecyclophenol polyethylene glycol ether 0.5%
disodium phosphate 1.0%
monosodium phosphate 0.5%
polyvinyl alcohol i.o%
water 56.7 ~; The ingredients are blended and ground together in a sand mill to produce particles substantially all under 5 microns in size.
Ezample M
Oil ~uspensi~on methyl 4-t3-(4-chlorophenyl)-1-[[(ethoxycarbonyl)-; (l-methylethyl)amino]thio]-N-[4-(trifluoromethyl)-phenyl~amino~carbonyl]-4,5-dihydro-lH-pyrazol-4-yl]benzoate. 35-0%
blend of polyalcohol carbo~ylic 6.0%
esters and oil soluble petroleum sulfonates xylene range solvent 59.0%
- .
.' ' ,:
': . .-2~00~30 The ingredients are combined and ground tegether in a sand mill to produce particles substantially all below 5 microns. The product can be used directly, e~tended with oils, or emulsified in water.
Example Emulsifiabl,e Concentrate methyl 7-chloro-2-[[N-[[[(hexylo~y)carbonyl]-methyl-amino]-thio]-N~[4-(trifluoromethyl)-phenyl]amino]-; carbonyl]-3,3a,4,5-tetrahydro-2H-benz[g]indazole-3a-., carboxylate. 5%
blend of oil soluble sulfonates , ' and polyoxyethylene ethers 4%
xylene 91%
,' The ingredients are combined and stirred with gentle warming to speed solution. A fine screen 20 filter is includ,ed in packaging operation to insure ;~
the absence of any extraneous undissolved material in ,:
the product.
~, Example O
~, 25 ~ettable Powder methyl 7-chloro-2-[[N-[[[(he~yloxy)carbonyl]-methyl- ''-' amino]-thio]-N-[4-(trifluoromethyl)-phenyl]amino]- - carbonyl]-3,3a,4,5-tetrahydro-2H-benz[g~indazole-3a-" carboxylate. 30%
- 30 sodium alkylnaphthalenesulfonate2%
, sodium ligninsulfonate 2%
synthetic amorphous silica 3%
, kaolinite 63% ', .
' . . .
,; .
2~)00130 .
The active ingredient, warmed to reduce viscosity, is sprayed onto the inert materials in a blender. After grinding in a hammer-mill, the material is reblended and sifted through a 50 mesh screen.
E~ample P
Solution methyl 7-chloro-2-[[N-[[[(he~yloxy)carbonyl]-methyl-amino]-thio]-N-[4-(trifluoromethyl)-phenyl]amino]-carbonyl]-3,3a,4,5-tetrahydro-2H-benz[g]indazole-3a-carboxylate. 10%isophorone 90%
- The ingredients are combined and stirred to -produce a solution suitable for direct, low volume application.
E~m~le O
Bait Granul~s methyl 4-[3-(4-chlorophenyl)-1-tt(ethoxycarbonyl)-(l-methylethyl)amino]thio]-N-[4-(trifluoromethyl)-phenyl]amino]carbonyl]-4,5-dihydro-lH-pyrazol-4-yl]benzoate. 3.0%
blend of polyethoxylated nonyl-9.0%
phenols an sodium dodecylbenzene r'~' benzene sulfonates ground up corn cobs 88.0%
The active ingredient and surfactant blend are dissolved in a suitable solvent such as acetone and sprayed onto the ground corn cobs. The granules are then dried and packaged. Compounds of Formula I, II and/or III can also be mi~ed with one or more oth2r insecticides, fungicides, nematocides, bactericides, acaricides, or other biologically active compounds to .-:
20(~0130 form a multi-component pesticide giving an even broader spectrum of effective pesticide protection.
Esamples of other agricultural protectants with which compounds of the present invention can be mixed or formulated are as follows.
Insecticides:
3-hydrosy-N-methylcrotonamide(dimethylphosphate)ester (monocrotophos) methylcarbamic acid, ester with 2,3-dihydro-2,2-: 15 dimethyl-7-benzofuranol (carbofuran) ; 0-[2,4,5-trichloro-a-(chloromethyl~benzyl]ophosphoric acid, 0',0'-dimethyl ester (tetrachlorvinphos) .
2-mercaptosuccinic acid, diethyl ester, S-ester with thionophosphoric acid, dimethyl ester (malathion3 phosphorothioic acid, 0,0-dimethyl, 0-D-nitrophenyl ester ~methyl parathion) methylcarbamic acid, ester with a-naphthol (carbaryl) -methyl 0-(methylcarbamoyl)thiolacetohydrosamate ; (methomyl) -25 N'-(4-chloro-Q-tolyl)-N,N-dimethylformamidine (chlordimeform) . ..
0,0-diethyl-0-(2-isopropyl-4-methyl-6-pyrimidylphos- ;
phorothioate (diazinon) .
`. octachlorocamphene (tosaphene) 30 0-ethyl 0-p-nitrophenyl phenylphosphonothioate (EPN~ , (S)-a-cyano-m-phenosybenzyl(lR,3R)-3-(2,2-dibromovinyl) -2,2-dimethylcyclopropanecarbosylate (deltamethrin) Methyl :
N',~'-dimethyl-N-t(methylcarbamoyl)oxy]-l-thioosamimi-date (osamyl) cyano(3-phenosyphenyl)-methyl-4-chloro-a-(1-methyl-ehtyl)benzeneacetate ~fenvalerate) ~-.
. ., ~ . . , -' ' ' . ': , :' '' 2;1~(30130 2~7 (3-pheno~yphenyl)methyl(~)-c s,trans-3-(2,2-dichloro .5 ethenyl)-2,2-dimethylcyclopropanecarbo~ylate (perme-thrin) a-cyano-3-pheno~ybenzyl 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carbosylate (cypermethrin) O-ethyl-S-(~-chlorophenyl)ethylphosphonodithioate lQ (profenofos) phosphorothiolothionic acid, :O-ethyl-0-[4-(methylthio)-phenyl]-S-n-propyl ester (sulprofos).
Additional insecticides are listed hereafter by their common names: triflumuron, diflubenzureon, methoprene, buprofezin, thiodicarb, acephate, azinphos-methyl, chlorpyrifos, dimethoate, fonophos, isofenphos, methidathio, methamidiphos, monocrotphos, phosmet, phosphamidon, phosalone, pirimicarb, phorate, profenofos, terbufos, trichlorfon, metho~ychlor, :~ bifenthrin, biphenate, cyfluthrin, fenpropathrin, ~ fluvalinate, flucythrinate, tralomethrin, metal- .
: dehyde and rotenone.
:
. methyl 2-benzimidazolecarbamate (carbendazim) -tetramethylthiuram disulfide (thiuram) : n-dodecylguanidine acetate (dodine) manganese ethylenebisdithiocarbamate (maneb) 1,4-dichloro-2,5-dimetho~ybenzene (chloroneb) methyl l-(butylcarbamoly)-2-benzimidazolecarbamate : (benomyl) .~, .
:, . . . ..
2V~ 30 1-[2-(2,4-dichlorophenyl)-4-propyl-1,3-dio~olan-2-ylmethyl3-lH-1,2,4-triazole (propiconazole) ~:
2-cyano-N-ethylcarbamoy-2-methoxyiminoacetamide (cymoxanil) 1-(4-chlorophenoxy)-3,3-dimethyl-1-(lH-1,2,4-triazol-1-yl)-2-butanone (triadimefon) N-(trichloromethylthio)tetrahydrophthalimide (captan) N-(trichloromethylthio)phthalimide (folpet) l-[[[bis(4-fluorophenyl)][methyl]silyl]methyl]-lH- .
1,2,4-triazole.
NematQcide~:
: 15 S-methyl l-(dimethylcarbamoyl)-N-(methylcarbamoyloxy)-thioformimidate : S-methyl ~ l-carbamoyl-N-(methylcarbamoyloxy)thioformimidate ` N-isopropylphosphoramidic acid, O-ethyl 0~-[4-(methylthio)-m-tolyl]diester (fenamiphos) Bac.~ericid~
tribasic copper sulfate streptomycin sulfate , .: 25 acariciaes:
senecioic acid, ester with 2-~Q~-butyl-4,6-dinitro-phenol (binapacryl) 6-methyl-1,3-cithiolo[4,5-B]quino~alin-2-one (oxythioquinox) ethyl 4,4'-dichlorobenzilate (chlorobenzilate) 1,1-bis(~-chlorophenyl)-2,2,2-trichloroethanol ; (dicofol) :
bis(pentachloro-2,4-cyclopentadien-1-yl) (dienochlor) tricyclohexyltin hydroxide (cyhexatin) :~ trans-5-(4-chlorophenyl)-N-cyclohexyl-4-methyl-2-oxo- ;
thiazolidine-3-carboxamide (hexythiazox) .
.. .. ~ . ... . . ..
.: . :.
.
Z~)0~:130 amitraz propargite fenbutatin-o~ide ~iologi~1 ~acillus thuringiensis Avermectin ~.
Utilitv The compounds of the present invention ex-hibit activity against a wide spectrum of foliar and soil-inhabiting, livestock, household and public health arthropods. Those skilled in the art will recognize that not all compounds will be equally ; effective against all arthropods but the compounds of : this invention display activity against economical-; ly important pest species, such as grasshoppers and 20 cockroaches including German or American roaches; ;
thrips; hemipterans: plant bugs (Miridae) such as tarnished plant bugs, lace bugs (Tingidae), seed bugs (Lygaeidae) such as cinch bugs, stink bugs (Pentatomidae), leaf-footed bugs (Coreidae) such as squash bug, and red bugs and stainers ~Pyrrocoridae) such as cotton stainer; also homopterans such as .~ whiteflies, aphids such as the green peach aphid, greenbug and cotton aphid, leafhoppers, spittlebugs . and planthoppers such as aster leafhopper, potato :~ 30 leafhopper and rice planthoppers, psyllids such as pear psylla, scales (coccids and diaspidids) and mealybugs; coleopterans including weevils such as boll weevil and rice water weevil, grain borers, chrysomellid beetles such as Colorado potato ~eetle, .
3S flea beetles and other leaf beetles, coccinellid beetles su~h ~s Me~ican bean beetle.
.
- . ., : ............... - .. . :: .. . - . . , ...... . ~ . .
, . . .. . ;:.~ .~ , . , -, , ., ,~ : - , , - . . -- . . . : . . ,. . .- . - : : -,. : ,. - . : . . : . :: . : - :
2V()0130 Activity is also shown against soil insects such as southern corn rootworm and wireworm;
lepidopterous larvae including noctuids such as fall armyworm, beet armyworm, other Spodoptera spp., Heliothis spp. such as virescens, Heliothis zea, cabbage looper, green cloverworm, velvetbean ; caterpillar, cotton leafworm, black cut- worm, and other noctuid cutworms and including pyralids such as . European corn borer, navel orange- worm, and :.
: stalk/stem borers and including tortricids like codling moth and grape berry moth as well as other .
lepidopterous larvae such as pink bollworm and diamodback moth; and dipterans such as leaf-miner, soil maggots, midges, and tephritid fruit . flies; house fly, Musca domestica; stable fly, Stomoxys calcitra.n~; black blow fly, Phormi-~ regin~;
face fly, ~u.sca autumn~l.is; black fly, Simulum 20 meri~ionale; yellow fever mosquito, Aedes eqypti; :.:
; German cockroach, Blattella aermanica; carpenter ants, :~ CamponQ~us pennsylvanicus and eastern subterranean ..
: termite, Reticulitermes flavipes. The pest control ` afforded by the compounds of the present invention is . 25 not limited, however, to these species.
The specific species, for which control is ~ esemplified below, are: fall armyworm, Spodoptera frugiperda; tobacco budworm, Heliothis virescens;
southern corn rootworm, Diabrotica undecimpunctata 3u howardi; aster leafhopper, Macrosteles fascifrons.
The pest control afforded by the compounds of the present invention is not limited, however, to these species.
Appliss~i9L
Arthropods are controlled in agricultural crops and animals and humans are protected by applying one or more of the compounds of this invention, in an ~, . .
Z~)~)013V
effective amount, to the locus of infestation, to the S area to be protected, directly to the pests to be controlled, or to their environment. A preferred method of application is by spraying with spray equipment that distributes the compound on the foliage, in the soil, or to the plant part that is infested or needs to be protected. AlternatiYely, granular formulations of these compounds can be applied to soil or foliage or, optionally, incorporated into the soil. Either aerial or ground i application can be used. Because of the diversity of behavior patterns and habitats of the animal and human health species, many different methods of application are employed. These include direct and residual - sprays, baits, ear tags, soil treatment and many others.
The pyrazoline compound(s) of this invention can be applied directly, but most often application will be of a formulation comprising one or more com-pounds of this invention, in an agriculturally suit-able carrier or diluent. A most preferred method of - 25 application involves spraying a water dispersion or refined oil solution of the compounds. The compound(s) can also be incorporated into baits which are consumed or in devices such as traps and the like that entice the arthropod to ingest or otherwise contact the to~icant compound(s).
The rate of application of Formula I, II or III compounds reguired for effective control will depend on such factors as the species of arthropod to be controlled, the pest's life stage, its 3ize, its location, the host crop, time of year of application, ambient moisture, temperature conditions, and the like. In general, application rates of 0.01 to 2 kg of active ingredient per hectare are sufficient ", '.
.
. . ' :, . ;.,~ - ,., , . , ~ . . . ~ , . : .. . . , . , , .... - .
:~ 2~00~30 . .
to provide effective control in large scale field operations under normal circumstances, but as little as 0.001 kg/hectare may be sufficient or as much as 8 kg/hectare may be required for agricultural use, or 0.1 mg/ft2 to 20 mg/ft2 for home use, depending upon the fact~rs listed above.
The following Examples demonstrate the con-trol efficacy of compounds of Formulae I, II and III
on specific arthropod pests wherein Compounds 1 through 55 are depicted in the Examples and Tables A, B and C and summarized in Table D, respectively.
, ~
- .
~ 20 ''- .
, , .
. 25 .
.
'~
.' ' .
:' ' ., : ' ' ' ' . ' , : :
- : . : -- . , : - , .
: - . ' .' ,' ' ' '' ~ ~
Table D
.
.. ' R2 ~ O2CH3 N-N
C-N ~ R~
o sY .:
-:
:
: CMPD Rl R2 Y
: 1 CF3 H N(CHtCH3]2)Co2Et ~ -. 2 CF3 H CO2~-Bu 3 CF3 H N(n-Bu)2 4 CF3 5-Cl N(CH3)CO2n-hexyl ~ 5 CF3 ~ N(CH3)cO2n-Bu : 6 CF3 H N(CH3)C2Et i;~ 7 CF3 4-F N(CH3)CO2n-~U
,. 8 CF3 - H N(CH3)CO2cyclohexyl 9 CF3 H N(cH3)co2n-octyl "r 30 10 CF3 H N(CH3)CO2n-decyl ~:.
'j 11 CF3 4-F N[CH(CH3)2]CO2Et . 12 CF3 H N(CH3)CO2n-dodecyl - 13 CF3 H N(CH3)CO2n-hexyl : 14 CF3 5-Cl CO2~-Bu CF3 5-Cl N[cH(cH3)2]co2Et 16 CF3 5-Cl N(CH3)CO2Et . . .
,: , .'', ''" .
"~ .
:.
' ' - ! r ' , .
.
, , - CMPD Rl R2 Y
. , _ . .
17 CF3 5-Cl N(CH3)C02n~octyl 18 CF3 4-F C02S-Bu : 19 CF3 5-Cl ~(CH3)C02n-Bu CF3 5-Cl N[CH3(CH3)2]C02n-BU
: 10 21 CF3 5-Cl N(cH3)co2n-dode 22 CF3 5-Cl N(cH3)co2cyclohe~yl 23 CF3 5-Cl N(CH3)C02(CH2)208U -:
24 CF3 5-Cl N(CH3)C02cl4H29 CF3 5-Cl N(CH3)C02c16H33 26 CF3 5-Cl N(CH3)C02c18H37 27 CF3 5-Cl N(CH3)C02c22H45 28 CF3 5-Cl N(cH3)co2(cH2)2o(cH2)2oBu .
.
:~ 20 :~ N ~
~`. 25 . -;
~s C--N~3R, ,., O SY , " , .'`'. '' :' ' - ', : .
.. . :
., , - . . . , . . , - . . . - , ,. . ; .. : . : : :
i ,' ' ' , " ". "', '' ': " ' ' ' ", ' ` ' ' :..... " ' ~ '' ~ .
.: . . .- : - . , ,-' , :,' ' , . ' :' ,' ' ,. . ;
- . . . ..
2~1Ul30 5 CMPD Rl R2 R3 Y
. . . _ 29 CF3 4-C1 4-F N[CH(CH3)2]C02Et .:
31 CF3 4-C1 4-F N[CH(CH3)2]CO2BU
32 CF3 4-C1 4-F N[cH(cH3)cH2cH3]co2Et 33 CF3 4-Cl 4-F C02~-Bu 10 34 CF3 4-C1 4-F N(CH3)CO2cyclohexyl .
:- .
~ [~R3 R2 /~
,,. N~N/
20 O'C~N~R, .. .' ' .
~'. 25 :
.... .
. CMPD Rl R2 R3 Q
CF3 4-C1 4-Cl SN[CH(CH3)2]COZEt CF3 4-C1 4-Cl SN(CH3)CO2s-Bu ;i 3036 CF3 4-C1 4-Cl SCOz~-Bu ~-~' 37 Cl 4-C1 4-Cl SCO2~-Bu ~: 38 CF3 4-C1 4-Cl CO2CH3 CF3 4-C1 4-Cl SN[cH(cH3)z]co2Et 9 3541 CF3 4-C1 4-Cl COCH3 . 42 4-C1 4-C1 4-F COCH3 ::
93 Br 4-C1 4-F COCH3 . ' , " ~
.
-2~00iL~ ~
CMPD Rl R2 R3 Q
CF3 4-C1 4-F COPh 46 CF3 4-C1 4-Cl COCH2CH3 47 CF3 4-C1 4-Cl COCOCH2CH3 : 48 CF3 4-C1 4-Cl COn-Bu 49 Cl 4-C1 4-Cl COCH3 ` 50 Cl 4-C1 4-Cl COCH2CH3 ; 51 Cl 4-C1 4-Cl CO2CH3 . 15 52 CF3 4-C1 4-Cl CO-4-Cl-Ph .` 53 CF3 4-C1 4-Cl COt-Bu 54 CF3 4-C1 4-Cl CO2Ph ~`.~ ;.
,.
~ 20 ,..
.,',. .
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:~25 ., .
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2~ 30 E~ample 56 Fall Armyworm S Test units, each consisting of an 8-ounce plastic cup containing a layer vf wheat germ diet, approx. 0.5 cm thick, were prepared. Ten third-instar larvae of fall armyworm (Spodoptera frugiperda~ were placed into each cup. Solutions of each of the test compounds (acetone/distilled water 75/25 solvent) were sprayed onto the cups, a single solution per set of three cups. Spraying was accomplished by passing the cups, on a conveyor belt, directly beneath a flat fan hydraulic nozzle which discharged the spray at a rate of O.S pounds of ~-~ active ingredient per acre (about 0.55 kg/ha) at 30 p.s.i. The cups were then covered and held at 27C
and 50% relative humidity for 72 hours, after which time mortality readings were taken.
Of the compounds tested on fall armyworm, the following resulted in greater than or equal to 80 mortality: 1, 2, 9, 5, 6, 7, 9, 10, 11, 12, 13, 16, 17, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 35, 36, 38, 41, 92, q3, 44, 45, 46, 47, 25 48, 49, 50, 51, 52, 53, and 54.
., .'~
Tobacco ~udworm The test procedure of Esample 56 was repeated for efficacy against third-instar larvae of the tobacco budworm (Heliothis virescens) e~cept that mortality was assessed at 98 hours. Of the compounds tested on tobacco budworm, the following resulted in greater than or equal to 80% mortality: 2, 4, 7, 11, 35 16, 17, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29;
30, 31, 32, 33, 35, 36, 38, 41, 42, ~3, 44, 45, 46, 48, 49, 50, 51, 52, 53 and 54.
., , , :
.
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: ' ' ' '.' .: ', ~ ' ' : ' ' ' `, ' ' ~ , '' , ~ ' . .' . , . " ~, ,,':
20(:~0:~3~) ~ampkQ_~
European Corn Borer Test units, each consisting of an 8-ounce - plastic cup containing a one-inch square of wheat germ/soyflour diet, were prepared. Five third-instar larvae of the European corn borer (Ostrinia nubilalis) were placed into each cup. Sets of three test units were sprayed as described in Example 56 with indi-vidual solutions of the test compounds. The cups were then covered and held at 27C and 50% relative humidity for 48 hours, after which time mortality readings were taken. Of the compounds tested on European corn borer, the following resulted in greater than or e~ual to 80% mortality: no testing.
E~ample 59 Southern Corn Rootworm Test units, each consisting of an 8-ounce plastic containing 1 sprouted corn (Zea mays) see, were prepared. Sets of three test units were sprayed as described in Example 56 with individual solutions of the test compounds. After the spray on the cups had dried, five third-instar larvae of the southern corn rootworm (Diabrotica undecimpunctata howardi) - were placed into each cup. A moistened dental wick was inæerted into each sup to prevent drying and the cups were then covered. The cups were then held at 27C and 50% relative humidity for 48 hours, after which time mortality readings were taken.
Of the compounds tested on southern corn rootworm, the following resulted in greater than or 35 equal to 80% mortality: 1, 2, 3, 4, 6, i, 9, 10, 11, 13, 16, 17, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, ^ 29, 30, 31, 32, 35, 36, 38, 41, Ç2, 44, 45, 47, 48, 49 and 51.
.
:,~
:- , , . -. . .. . : :,. . .
;~ , :
. .
E~ample ~0 Aster Leafhopper Test units were prepared from a series of 12-ounce cups, each containing oat (Avena ~ativa) seedlîngs in a l-inch layer of sterilized soil. Sets of three test units were sprayed as described in Example 56 with individual solutions of the below-listed compounds. After the oats had dried from the spraying, between 10 and 15 adult aster leafhoppers ; (Mascrosteles fascifroms) were aspirated into each of 15 the cups. The cups were held at 27C and 50% relative ~
humidity for 48 hours, after which time mortality -readings were taken.
Of the compounds tested on aster leafhopper, the following resulted in greater than or equal to 80% !~
20 mortality: 1, 2, 3, 9, 6, 7, 8, 9, 10, 11, 12, 13, ` 16, 17, 19, 20, 21, 22, 23, 24, 25, 26, 28, 30, 31, 35, 36, 38, 41, 42, 43, 44, 45, 47, 49, 50 and 51.
: .
Ex~mDle 61 Boll Weevil - Five adult boll weevils (Anthonomus grandis) were placed into each of a series of 9-ounce cups.
The test procedure employed was then otherwise the same as in Esample 56 with three cups per treatment.
Mortality readings were taken 48 hour~ after treatment.
` Of the compounds tested on boll weevil, the following resulted in greater than or equal to 80%
mortality: 16, 21, 22, 23, 24, 25, 26, 27, 28, 30, 35, 36, 38, 41, 42, 43, 44, 46, 48, 49, 50, 51, 52 and 54.
. , .
: : . :
,. . . .: . . . . : ~, :. .. .. .... .. ~ - . :
19 7-Cl ~(CH3)C(O)OC4H9 125-127 0.82(m,3H), 1.2(m,4H), l.9~m,1H), 2.65(m,1H), 2.85(m,2H), 3.5(6,3H), 3.66(~,3H), 3.75(m,3H), 4.45(d,lH), 7.05(m,3H), 7.35(d,2H), 7.6(d,2H).
7-Cl NlcH(cH3)2lc(o)oc4H9 - 0.84(t,3H), 1.25(m,10H), l.9(m.lN), 2.65~m,lH), 3.~6~c~3K), 3.7~m.3H).
4.45(m,2B), 7.15(m,2H), 7.4(m,3H), 7.6(d,2H).
i, .
Z~'(!13~0 Example R2 Z m.p.-C lH NMR (~ in ppm) ~ CDC13 21 7-Cl N( Q 3)C(O)ocl2H2~5 0.88(t,3H), 1.2(m,20H), l.9(m,1H), 2.65(m,1H), - 2.9~m,2H), 3.5(s,3H), 3.67(6,3B), 3.75(m,3H), 4.5(d,1H), 7.05(m,3H), 7.35(d,2H), 7.6(d,2H).
22 7-Cl N(CH3)C(O)O-cycloC6H11 87-91 0.8-1.7(Bro~d m,lOH), ; 2.65(m,1H), 2.9(m,2H), 3.51(s,3H), 3.66(s,3H), 3.75(d,lH), 4.35(m,lH), 4.q5(d,1H), 7.05(m,3H), 7.35(d,2H), 7.6(d,2H).
23 7-Cl N(CH3)C~0)0(CH2)20C4H9 ~ 0.9 ~t,3H), 1.4 (m,4H) - 20 1.9 (m,lH), 2.7 (m,lH) 2.9 (m,2H), 3.3 (m,4H) 3.5 (6,3H), 3.67 (~,3H), 3.9 (m,3H), 4.5 (d,lH), ~i 7.1 (m,3H), 7.4 (d,2H), 7.6 (d,2H).
``~ 24 7-Cl N(CH3)~(O)OC14H29 - 0.87 (t,3H), 1.26 (m,24H), ` 1.9 (m,lH), 2.65 (m,lH), - 2.9 (m,2H), 3.5 (~,3H), 3.68 ~,3H), 3.75 (m,3B), ~.47 (~,1H), 7.05 tm,3H), -~ 7.35 (d,2H), 7.57 (d,2H).
- 25 7-Cl N~CH3)C(O)OC16H33 ~ 0.87 (t,3H), 1026 (m,28H), ~ -1.9 (m,lH), 2.65 (m,lB), 2.9 (m,2H), 3.5 ~,3H), 3.67 (~,3H), 3.75 (m,3H), 4.47 (d,lB~, 7.05 (m,3H), 'I`
7.35 (a,2H), 7.6 (d,2H).
, : . .
.~,, Zl~Q130 ::
Ex~mple R2 Z m.p.-C lH NMR (6 in ppm) ~ D CDCl3 .
26 7-Cl N(cH3)c(o)ocl8H37 0.9 tt,3H), 1.26 (m,32H), ` 1.9 (m,lH), 2.65 (m,lH), 2.9 (m,2H), 3.5 (s,3H), 3.67 ~m,3H), 3.75 (m,3H), 4.5 (d,lH), 7.05 (m,3H), 7.35 ld,2H), 7.6 (d,2H~.
27 7-Cl N(cH3)c(o)oc22H45 O.BB (t,3H), 1.26 (m,40~, l.9 (m,lH), 2.65 (m,lH), 2.9 (m,2H), 3.5 (s,3H), 3.6~ (m,3H), 3.75 (m,3H), 4.4B (d,lH), 7.06 (m,3H), ' 7.3~ (d,2H), 7.6 (d,2H).
~`~ 28 7-Cl N~cH3)c(o)o(cH2)2o(cH2)2oc4Hg 0.91 (t,3H), 1.4 (m,4H), l.9 (m,lH), 2.i (m,lH), ~ 2.9 (m,2H), 3.5 (s,3H), -~ ` 3.67 (s,3H), 3.7 (m,9H). 7.
~ 4.0 (m,lH), 4.2 (m,lH).
.-1 4.5 (d,lN), 7.6 (m,3H), 7.4 (d,2H), 7.6 (d,2H).
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E~ample 29 1-(4-chlorophenyl)-5-(9-fluorophenyl)-4,5-dihydro-N-t4-(trifluoromethyl)phenyl]-N-[N~ methylethyl)-N~-(etho~ycarbonyl)aminothiol~-lH-pyrazole-3-carb~amide Step A: Ethyl (chlorosulfenyl)(l-methylethyl)-carbamate To a solution of ethyl (l-methylethyl)carbamate (13.1 9, 0.1 mol) in lO0 ml of methylene chloride cooled to 0C was added sulfur dichloride (11.3 9, 0.11 mol) in one portion. While maintaining the temperature of the mixture at 0C, pyridine (8-? 9, 0.11 mol) was added dropwise over eleven minutes.
After complete addition of the pyridine the temperature was allowed to rise to room temperature and stirring was continued ~or additional 1.5 hours.
The mi~ture was let stand overnight. Methylene chloride was evaporated under vacuum and 100 ml hexane was added. Filteration of pyridine hydrochloride and evaporation of he~ane resulted in an orange oil which was distilled in a Kugelrohr apparatus to give 12.5 9 of the title Compound ~.P.:
69-B0 (bath temp.) .; 1,,~,.
Step B: 1-(4-chlorophenyl)-5-(4-fluorophenyl)-4,5-dihydro-N-14-(trifluoromethyl)phenyl~- -N-tN'-(l-methylethyl)-N'-(ethoxycarbonyl)-ol] IH-pyrazole-3-Farbosamide To a solution of 1-(4-chlorophenyl)-5-(~-fluoro-phenyl)-4,5-dihydro-N-14-(tri~luoromethyl)phenyl]-lH-pyrazole-3-carbo~amide (0.95 g, 0.002 mol) in 10 ml .. , " ,' .
:
-,~ . ' Z~lt!130 of methylene chloride cooled to 0C was added triethylamine (0.25 9) followed by the title compound of Step A (0.5 9, 0.0025 m~l). The reaction mi~ture was all~wed to warm to room temperature with ~tirring for one hour. Methylene chloride (50 ml) was added and the mi~ture was washed with water, dried over magnesium sulfate and filtered. The ~olvent was evaporated and the residue was purified by silica gel column chromatograph using he~ane:ether (2:1) 95 the ; eluent. Obtained 1.0 9 of the title compound, m.p.: 136-137DC, 'H-NMR (CDC13): ~ 7.7 (d,2H), ~.4 (~, 2H), 7.0 (m, 6H), 6.3 (d, 2H), 5.2 (d of d, lH~, 4.5 (m, lH), 3.75 (m, 3H), 3.05 (d of ~, lH) 1.3 (d of d, 6H), ~.87 (t, 3H).
E~ample 30 3,4-bis-(9-chlorophenyl)-N-[4-(trifluoromethyl)-phenyl]-N-[N'-(l-methylethyl)-N'-(etho~ycarbonyl)-aminothioll-9~5-dih~dro-lH-pyraz~le-l-carbo~mide , T~ a solution of 3,4-bis-(4-chlorophenyl)-N-[9-(trifluoromethyl)phenyl)]-4,5-dihydro-lH-pyrazole-2S l-carbo~amide (Q.466 9, ~.001 mol) in 5 ml of methylene chloride cooled to 0C was added 0.3 9 of triethylamine and ethyl (chlorosulfenyl)(l-methyl-`i ethyl)carbamate (0.5 9). The mi~ture was allowed to warm to room temperature and let stand overnigh~. 20 ml CH2C12 was added and the mi~ture was washed with water ad dried over MgSO4 and filtered. The solvent ;
was evaporated under vacuum. The residue was purified by silica gel column chromatogr~phy using CH2C12:Butylchloride mi~ture (1:1) ~s a primary eluent followed by ether. The title compound was obtained in high purity (0.28 9), m.p.: 65-68C.
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. :,,: ' ' ., ~ 30 : 36 lH-NMR (CDC13), ~ 7.65 (d, 2H), 7.5 (d, 2H~, 7.27 (d, 2H), 7.17 (S, QH), 7.0 (d, 2H), 4.6-4.3 (m, 3H), 3.95 5(d-of d, lH), 3.8 (q, 2~), 1.3 (m,-6H), 0.95 (t, 3H).
The following additional E~amples (Tables B
and C) employed procedures similar to those described in the previous E~amples 29 and 30 ~r in the -~ 10 disclosed literature.
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Cl ~ N S
rJ~cr3 - Example X m.p.C 'H-NMR ~ ln ppm) in CDC13 : .
31N[cH(cH3)2lc(o)oc4H9 165-170 7.23 ~d, 2H), 7.4 ~a, 2H), 7.0 lM, 6H), 6.3 (d, 2H), 5.2 (d of d, lH), 4.5 ~M, lH), 3.75 (M, 3H), 3.1 (d of d, lH), 1.4 2~ ~M, lOH), .85 (t, 3H) 32NlcN(cH3)(c2H5)]c(o)oc2H5 ~ 7.23 (d, 2N), 7.4 ~d, 2H), ., 7.0 ~M, 6H), 6.3 (d, 2H), 5.2 (d of ~, lH), 4.5 lM, lH), 3.75 (M, 3H), 3.1 (d of d, lH), 1.8 (M, SH), 0.9 (M, 6H).
. .
~ 35 .. ..
.
,, 2~ 30 Example X m.p.C 'H-NMR ~ ~n ppm) ln CDCl~
. _ 33 C(O)OCHtCH3)(C2H5) 159-161 7.25 (d, 2H), 7.55 (d, 2H), 7.0 (M. 6H), 6.25 (d, 2H), 5.2 (d of d, lH), 5.0 (M, lH), 3.75 (d of d, lH), 3.1 (d of d, lH), 1.65 (M, 2H), 1.28 (d, 3H), 0.9 (t, 3H).
34 N(CH3)C(O)O(cyclo C6Hll) 147-150 7.2 (d, 2H), 7.4 (d, 2H), 7.0 (M, 6H), 6.3 ta, 2H), 5.2 (d of d, lH), 4.3 -~ (M, lH), 3.7 (d of d, lH), 3.5 (5, 3H~, 3.2 (d of d, lH), 1.3-0.9 (M, lOH).
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~''' ,' " '' ' '' ', ', ,,' ' ,' ' " ~'" '"';" ' ""'' ' ' . ' "' ''', ' ", " ' '' . ' ' ;'; ' ' ' '': ' ' ' :.'.' :' . .' '. "" ' ' . . . , ', ' - ' ' - , . :' ' ' ',, . .' .. . ' . ' ' .: ': . : ,'' :. ,'.' '.' ' ' ' . ,. ' ' ,' ' . ' .: . ' ' : . ' ' , ' ' ~' ' ' ;"';,'' ' ' '' '' ' , ,' " ,''" .'. ' ''' , '. . ' . ' : . " ' ' ' - ' ' ':' ` '' '' ' . ' ". ' ' ' ~ ~3C~
.
~ble C
0 C~ ~R3 ~'`.' )~ , : N~N
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:. R~ . -, :,'' :~,.
, 20 .. ~, .
i ~LE Q R3 Rl m.p.C 'H-NMR (6 in ppm) . . :
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.,; 35 5-N~CH3)C~0)0-cec-C4H9 Cl CF3 83-84 7.8-6.9 (m, 12H), . ,.3 ~ . 6-4 . 3 (M, 3H ), 4 . 0 ':
' (M, lH), 3.52 (S, 3H), 1.25 (M, 2H), 1.0--0.7 (M, 6H ) .
~.:
36 S-C(0)0-cec-C4Hg Cl CF3 78-60 7.7-7.0 (M, 12H), 5.0 ., (M, lH), ~1.45 (M, 2H), ~,, .
` ~.0 ~M, lB), 1.6 (M, .~ 2N), 1.3 ~d, 3H), 0.9 .. . .
: ~t, 3N).
: 3 5 ,. : .
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?130 EX- Q R3 Rl m.p.-C 'H-NMR (6 in ppm) AMPLE _ _ 37 S-C(O)O-6ec-CqNg Cl Cl 66-69 7.4-6.9 (M, 12H), 5.0 (M, lH), 4.5 (M, 2H), 4.0 (M, lH), 1.6 (M, 2H), 1.28 (d, 3H), 0.9 (M, 3H).
: .
; 38 CO2CH3 Cl CF3 151-154 7.7-7.0 (m, 12H), 4.7 ~d,d,lH), 4.5 (d,d,lH), 4.1 (d,d,lH), 3.86 ; (s,3B).
39 COCH3 F CF3 157-159 7.7-7.0 (m,12H), 4.7 (d,d,lH), 4.5 (d,d,lN), 4.1 (d,d,lH), 3.86 (~,3H).
S-N(cH(cH3)2)so2c2H5 Cl CF3 oil 7.65 (m,2H), 7.25 (m,4H), 7.05 (m,lH), 4.6-3.9 (m,3H), 3/65 (m,lH), 3.03 ` (q,2H), 1.36 (t,3H), 1.24 , (d,6H1-41 COCH3 Cl CF3 166-168 7.6-7.0 (m,12H), 4.7-4.0 (m,3H), -2.3 (~,3H).
. ' ~2 COCH3 F Cl 187-190 ~.5-7.0 ~m,12H), .6 (m,lN), 4.4 (m,lH~, 4.0 (m,lH), 2.26 (s,3H).
"
,. .
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. . .
2~ 30 5 EX- Q R3 Rl m.p.-C 'B-NMR (~ ln ppm UMPLE __ _ Ç3 COCH3 , F Br181-186 7.6-7.0 (m,12H), 4.65 (m,lH), 4.4 (m,lN), ^ 10 q.0 (m,lH~, 2.25 ~,3H).
44 CO2Me F CF380-86 COPh F CF3176-179 46 COEt Cl CF3 169-170 , 47 EtCOCO Cl CF3 166-167 48 CO-~-Bu Cl CF3 60-62 ~ 49 COCH3 Cl Cl io5-206 .' . .
~ 25 50 COEt Cl Cl157-158 , .
51 CO2Me Cl Cl162-166 52 4-ClPhCO Cl CF3209-211 , ~0 53 t-BuCO Cl CF3140-145 :,.
54 PhOCO Cl CF3150-155 , ,~ 35 .' ' ~', ~', .
. ~ .
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2~ 130 Example 5S
- N~acetyl-3,4-bist4-chlorophenyl)-4,5-dihydro-N-[4-(trifluoromethyl)phenyl]-lH-pyrazole-l-__~lk~smi~e ' .
The compound of Step D of Esample 6 (0.65 9) was dissolved in tetrahydrofur~n ~20 ml) and treated with 60% sodium hydride in oil (0.12 9). After the - evolution of hydrogen was complete (30 minutes), acetic an~ydride (D.6 ml) was ~dded and the misture was stirred at room temperature for 16 hours. The reaction was diluted with saturated agueous ammonium chloride solution (15 ml) and ethyl acetate (30 ml).
~` The organic layer was dried with magnesium sulfate and evaporated. The residue was subjected to chromatography on silica gel with he~anes/ethyl acetate (3:1) as eluent. Addition of methanol (10 ml) to the product gave, after filtration, the title compound (0.4 9). m.p. 166 to 168~C.
NMR (CDC13) 7.6-7.0 (m, ArH, 12H), 4.7-4.0 (m, 3H, CH and CH2), 2.3 (s, COCH3, 3H).
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211t~0130 Table 1 : 5 .
N~
~N J~R
S--N
R~, : 15 . . Rl R2 B R8 Rg 4-CF3 5-Cl H Me OEt ~ 4-CF3 5-Cl Me Me OEt 9-CF3 H CO2Me Me OEt . 4-Cl H CO2Me Me OEt :
4-Br H CO2Me Me OEt 4-OCP3 H CO2Me Me OEt . 4-CF3 5-Cl CO2Me Me OEt 4-C1 5-Cl CO2Me Me OEt ~ .
4-OCF3 5-Cl CO2Me Me OEt 4-CF3 5-CP3 C~2Me Me OEt 4-CF3 5-F CO2Me Me OEt .
4-CE3 5-Cl Ph Me OEt . 30 4-CF3 5-C1 9-Cl-Ph Me OEt :; 4-CF3 5-Cl CO2Et Me OEt . 4-CF3 5-Cl H Me O-n-Bu :' 4-CF3 4-F ~ Me O-n-Bu 4-CF3 H Me Me O-n-Bu . 35 4-CF3 5-Cl Me Me O-n-Bu 4-CF3 5-Br Me Me O-n-Bu 2~0~130 Rl R2 B R~ Rg .
4-CF3 4-F Me Me O-n-Bu 4-CF3 H COzMe Me O-n-Bu 4-Cl H C02Me .Me O-n-Bu 4-~r H CO2Me Me O-n-Bu 4-OCF3 H CO2Me Me O-n-Bu 4-CF3 5-Cl CO2Me Me O-n-Bu -~
4-C1 5-CI CO2Me Me O-n-Bu 4-Br 5-Cl CO2Me Me O-n-Bu 4-OCF3 5-Cl CO2Me Me O-n-Bu 9-CF3 5-Br CO2Me Me O-n-Bu 9-C1 5-Br CO2Me Me O-n-~u .
4-Br 5-Br CO2Me Me O-n-Bu 4-OCF3 5-Br CO2Me Me O-n-Bu 9-CF3 4-F CO2Me Me O-n-Bu 4-C1 4-F CO2Me Me O-n-Bu :
4-Br 4-F CO2Me Me O-n-8u 4-OCF3 4-F CO2Me Me O-n-Bu 4-CF3 5-CF3 CO2Me Me O-n-Bu .`
4-CF3 5-P CO2Me Me O-n-Bu .~! 25 4-CF3 5-Cl Ph Me O-n-Bu .. ~ 4-CF3 5-C1 4-Cl-Ph Me O-n-Bu 4-CF3 S-Cl ~O2Et Me O-n-Bu ~. 4-CF3 5-Cl Me Me O-n-hexyl ~ 4-CF3 H CO2Me Me O-n-he~yl 4 Cl H CO2Me ~e O-n-hesyl , 4-Br H CO2Me Me O-n-hexyl 4-OCF3 H CO2Me Me O-n-he~yl .~, 4-CF3 S-Cl C02Me Me O-n-he~cyl 4-C1 5-C1 C02Me Me O-n-he~yl .. ..
`~ 4-Br 5-Cl CO2Me Me O-n-he~yl ..
4-OCF3 5-Cl CO2Me Me O-n-hesyl 4-CF3 5-~r C02Me Me O-n-he~yl .... .
': ;
. '',' :-Z~ 130 . ~
Rl R2 B R8 Rg 4-C1 5-Br CO2Me Me O-n-he~yl 4-~r 5-Br CO2Me Me O-n-he~yl 4-OCF3 5-Br CO2Me Me O-n-he~yl 4-CF3 4-F CO2Ne Me O-n-hesyl 4-C1 4-F CO2Me Me O-n-hexyl 4-Br 4-F CO2Me Me O-n-hesyl 4-OCF3 4-F CO2Me Me O-n-he~yl 4-CF3 5-CF3 CO2Me Me O-n-he~yl 4-CF3 5-F CO2Me Me O-n-hesyl 4-CF3 5-Cl Ph Me O-n-hexyl 4-CF3 5-C1 4-Cl-Ph Me O-n-he~yl 4-CF3 5-Cl CO2Et Me O-n-he~yl 4-CF3 S-Cl Me Me O-n-octyl . 4-CF3 H CO2Me Me O-n-octyl , 20 4-Cl H CO2Me Me O-n-octyl ; 4-Br H CO2Me Me O-n-octyl 4-OCF3 H CO2Me Me O-n-octyl ~ 4-CF3 5-Cl CO2Me Me O-n-octyl ; 4-C1 5-Cl CO2Me Me O-n-octyl 4-Br 5-Cl CO2Me Me O-n-octyl ~ 4-OCF3 5-Cl CO2Me Me O-n-octyl .~. 4-CF3 5-Br CO2Me Me O-n-octyl 4-C1 5-Br CO2Me Me O-n-octyl 9-Br 5-Br CO2Me Me O-n-octyl 4-OCF3 5-Br CO2Me Me O-n-octyl 4-CF3 4-F CO2Me Me O-n-octyl 4-C1 4-F CO2Me Me O-n-octyl 4-Br 4-F CO2Me Me O-n-octyl 4-OCF3 4-F CO2Me Me O-n-octyl 4-CF3 5-CF3 CO2Me Me O-n-octyl 4-CF3 5-F C2Me Me O-n-octyl ,~
., , .:
~6 Rl ~2 B RB ~9 :.
4-CF35-Cl Ph Me O-n-octyl 4~CF35-C14-Cl-Ph Me O-n-octyl 4-CF35-Cl c02Et Me O-n-octyl g-CF35-Cl Me Me O-n-decyl 4-CF3 H CO2Me Me O-n-decyl 4-Cl H CO2Me Me O-n-decyl 4-Br H CO2Me Me O-n-decyl 4-OCF3 H CO2Me Me O-n-decyl 4-CF35-Cl CO2Me Me O-n-decyl 4-C15-Cl CO2Me Me O-n-decyl ..
~-Br 5-Cl CO2Me Me O-n-decyl 4-OCF35-Cl CO2Me Me O-n-decyl .
. 4-CF35-Br CO2Me Me O-n-decyl 4-C15-Br CO2Me Me O-n-decyl ; 20 4-Br 5-Br CO2Me Me O-n-decyl 4-OCF35-Br C2Me Me O-n-decyl `- 4-CF34-F CO2Me Me O-n-decyl 4-C14-F CO2Me Me O-n-decyl 4-Br 4-F CO2Me Me O-n-decyl 4-OCF34-F CO2Me Me O-n-decyl :
~,. 4-CF35-CF3 CO2Me Me O-n-decyl .. 4-CF35-~ CO2Me Me O-n-decyl 4-CF35-Cl Ph Me O-n-decyl -.................. 4-CF35-C14-Cl-Ph Me O-n-decyl ::
4-CF35-Cl Co2Et Me O-n-decyl :: 4-CF35-Cl Me Me O-n-dodecyl . 4-CF3 H CO2~e Me O-n-dodecyl .
: 4-Cl H CO2Me Me O-n-dodecyl :
.. 4-Br H CO2Me Me O-n-dodecyl ~::
4-OCF3 H CO2Me Me O-n-dodecyl :
4-CF35-Cl CO2Me Me O-n-dodecyl ., .
., .: : . : . .. . . . ~
2'~ ?130 Rl R2 - -_8 9_ 4-C1 5-Cl CO2Me Me O-n-dodecyl 4-8r 5-Cl CO2Me Me O-n-dodecyl 4-OC~3 5-Cl CO2Me Me O-n-dodecyl 4-CF3 5-Br CO2Me Me O-n-dodecyl 4-C1 5-~r CO2Me Me O-n-dodecyl 4-Br 5-Br CO2Me Me O-n-dodecyl 4-OCF3 5-~r CO2Me Me O-n-dodecyl 4-CF3 4-F CO2Me Me O-n-d~decyl 4-C1 4-F CO2Me Me O-n-dodecyl 4-Br 4-F CO2Me Me O-n-dodecyl 4-OCF3 4-F CO2Me Me O-n-dodecyl 4-CF3 5-CF3 CO2Me Me O-n-dodecyl - 4-CF3 5-F CO2Me Me O-n-dodecyl 4-CF3 5-Cl Ph Me O-n-dodecyl ; 20 4-CF3 5-C1 4-Cl-Ph Me O-n-dodecyl 4-CF3 5-Cl CO2Et . Me O-n-dodecyl 4-CF3 5-Cl Me Me O-sec-Bu 4-CF3 iH CO2Me Me O-sec-Bu . 9-Cl H CO2Me Me O-sec-Bu 4-Br H CO2P~e Me O-sec-Bu . 4-OCF3 H CO2Me Me O-sec-Bu 4-CF3 5-Cl CO2Me Me O-sec-Bu 4-C1 5-Cl CO2Me Me O-sec-Bu 4-Br 5-Cl CO2Me Me O-sec-Bu 4-OCF3 5-Cl CO2Me Me O-sec-Elu 4-CF3 5-Br CO2Me Me O-sec-Bu 4-C1 5-Br CO2Me Me O-~ec-Bu 4-Br 5-Br CO2Me Ne O-sec-Bu 4-OCF3 5-Elr CO2Me Me O-sec-Bu 4-CF3 4-F CO2Me Me O-sec-Bu 4-C1 4-F CO2Me Me O-sec-Bu , ,. . .
:, . , , . . . :
2~ 130 Rl R2 ~ R8 Rg 4-Br 4-F CO2Me Me ~-~ec-Bu 4-OCF34-F CO2Me Me O-sec-Bu 4-CF35-CF3 CO2Me Me O-sec-Bu 4-CF35-F CO2Me Me O-sec-~u 4-CF3 5-Cl Ph Me O-sec-~u 4-CF35-C14-Cl-Ph Me O-sec-Bu 4-CF3 5-Cl CO2Et Me O-sec-~u 4-CF35-Cl Me Me OCH2CH20Et . 4-CF3 H CO2Me Me OCH2CH20Et :~ 15 4-Cl H CO2Me Me OCH2CH20Et 4-Br H CO2Me Me OCH2CH20Et 4-OCF3 H CO2Me Me OCH2CH20Et .. 4-CF35-Cl CO2Me Me OCH2CH20Et `~ 4-C15-Cl c02Me Me OCH2CH20Et 2~ 4-~r 5-Cl CO2Me Me OCH2CH20Et 4-OCF35-Cl CO2Me Me OCH2CH20Et 4-CF35-Br CO2Me Me OCH2CH20Et 4-C15-Br CO2Me Me OCH2CH20Et 4-Br 5-Br CO2Me Me OCH2CH20Et 4-OCF35-Br CO2Me Me OCH2CH20Et . 4-CF34-F CO2Me Me OCH2CH20Et ` 4-C14-F ~2Me Me OCH2CH20Et ` 4-Br 4-F CO2Me Me OCH2CH20Et .~ 4-OCF34-F CO2Me Me OCH2CH20Et 4-CF3 S-CF3 C02Me Me OCH2CH20Et 4-CF35-F CO2Me Me OCHiCH20Et 4-CF3 5-Cl Ph Me OCH2CH20Et 4-CF3 5-C1 4-Cl-Ph Me OCH2CH20Et 4-CF35-Cl C02Et Me OCH2CH2~Et 4-CF35_Cl Me Me OCH2CC13 .. '! 4-CF3 H CO2Me Me OCH2CC13 4-Cl H CO2Me Me OCH2CC13 .~ 4-Br H CO2Me Me OCH2CC13 ~-':~
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Zt~(?c~130 .
1 R2 B R8 Rg 4-OCF3 H CO2Me Me OCH2CC1 4-CF3 5-Cl CO2Me Me OCH2CC1 4-C1 5-Cl C~2Me Me OCH2CC1 4-Br 5-Cl CO2Me Me OCH2CC1 4-OCF3 S-Cl CO2Me Me OCH2CC1 4-CF3 5-Br CO2Me Me OCH2CC1 4-C1 5-Br CO2Me Me OCH2CC1 4-Br 5-Br CO2Me Me OCH2CC1 4-OCF3 5-~r CO2Me Me OCH2CC1 4-CF3 4-F CO2Me Me OCH2CC1 4-C1 4-F CO2Me Me OCH2CC1 4-Br 4-F CO2Me Me OCH2CC1 4-OCF3 4-F CO2Me Me OCH2CC1 4-CF3 5-CF3 CO2Me Me OCH2CC1 4-CF3 5-F CO2Me Me OCH2CC1 - 4-CF3 5-Cl Ph Me OCH2CC1 4-CF3 5-C1 4-Cl-Ph Me OCH2CC1 4-CF3 5-Cl CO2Et Me OCH2CC1 4-CF3 5-Cl Me Me OCH2CF3 4-CF3 H CO2Me Ne OCH2CF3 .``~ 9-Cl H CO2Me Me OCH2CF3 4-Br H CO2Me Me OCH2CF3 -~ 4-OCF3 H CO2Me Me OCH2CF3 :- 4-CF3 5-Cl CO2Me ~e OCH2CF3 4-C1 5-Cl CO2Me Me OCH2CF3 4-Br 5-Cl CO2Me Me OCH2CF3 4-OCF3 5-Cl CO2Me Me OCH2CF3 4-CF3 5-~r CO2Me Me OCH2CF3 ; 4-Cl S-Br CO2Me Me OCH2CF3 : 35 4-Br 5-~r CO2Me Me OCH2CF3 4-OCF3 5-Br CO2Me Me OCH2CF3 :. ~
. . ~
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.. . .
1 R2 ~ R8 Rg ~ 4-CF34-F CO2Me Me OCH2CF3 : 4-C14-F CO2Me Me OCH2CF3 4-Br 4 F CO2Me Me OCH2CF3 9-OCF34-F CO2Me Me OCH2CF3 4-CF35-CF3 CO2Me Me OCH2CF3 4-CF35-F CO2Me Me OCH2CF3 ~ 4-CF35-Cl Ph Me OCH2CF3 :. 4-CF35-C14-Cl-Ph Me OCH2CF
4-CF35-Cl CO2Et Me OCH2CF3 :~ lS 4-CF35-Cl Me Me OCH2CO2Et 4-CF3 H CO2Me Me OCH2~O2Et 4-Cl H CO2Me Me OCH2CO2Et 4-Br H C2M~ Me OCH2CO2Et 4-OCF3 H CO2Me Me OCH2CO2Et ~ 20 4-CF35-Cl CO2Me Me OCH2CO2Et .~- 4-C15-Cl CO2Me Me OCH2CO2Et ~` 4-Br S-Cl CO2Me Me OCH2CO2Et 4-OCF35-Cl CO2Me Me OCH2CO2Et -, 4-CF35-Br CO2Me Me- OCH2CO2Et 4-Cl S-Br CO2Me Me OCH2CO2Et .~. 4-Br 5-8r CO2Me Me OCH2CO2Et 4-OCF35-Br CO2Me Me OCH2C2Et ~ 4-CF34-F CO2Me Me OCH2CO2Et .~ 4-C14-F CO2Me Me OCH2CO2Et 4 Br 4-F CO2Me Me OCH2CO2Et 4-OCF34-F CO2Me Me OCH2CO2Et . 4-CF35-CF3 CO2Me Me OCH2CO2Et 4-CF35-F CO2Me Me OCH2CO2Et 4-CF35-Cl Ph Me OCH2CO2Et 4-C~35-Cl 4-Cl-Ph Me OCH2CO2Et 4-CF35-Cl CO2Et Me OCM2COzEt :
, ;. - . . .
Z~Q0130 Rl R2 B R8 Rg 4-CF3 H H Me F
4-CF3 5-Cl H Me F
- 4-CF3 5-Br H Me F
4-CF3 4-F H Me F
4-CF3 H Me Me F
4-CF3 5-Cl Me Me F
. 4-CF3 5-Br Me Me F
4-CF3 4-F Me Me F
. 4-CF3 H CO2Me Me F
4-Cl H CO2Me Me F
4-Br H CO2Me Me F
4-OCF3 H CO2Me Me F
4-CF3 5-Cl CO2Me Me F : -~. 4-C1 5-Cl CO2Me Me :.: 20 4-Br 5-Cl CO2Me Me F
4-OCF3 5-Cl CO2Me Me F
. 4-CF3 5-~r CO2Me Me F
4-C1 5-Br CO2Me Me F
4-Br 5-Br CO2Me Me F
4-OCF3 5-Br CO2Me Me F
4-CF3 4-F ~O2Me Me F
4-C1 4-F CO2Me Me F
4-Br 4-F CO2Me Me F
4-OCF3 4-F CO2Me Me F
4-CF3 5-CF3 CO2Me Me F
4-CF3 5-F CO2Me Me F
~ 4-CF3 5-Cl Ph Me F
: 4-CF3 5-C1 4-Cl-Ph Me F
4-CF3 5-Cl CO2Et Me F
4-CF3 5-Cl CO2Me Me piperidino 4-CF3 4-F Me Me piperidino 4-CF3 Cl CO2Me Me morpholino .'' ' ~
"
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Z~-~U0:130 .. .
.
Rl R2 B R8 Rg 4-OCF3 Cl CO2Me Me m~rph~lino 4-CF3 5-Cl CO2Me Me n-Pr 4-OCF3 5-Cl CO2Me Me n-Pr 4-CF3 5-Br CO2Me Me sec-~u 4-C1 5-Br CO2Me Me ~ec-Bu 4-Br 5-Br CO2Me Me sec-Bu ; 4-OCF3 5-Br CO2Me Me sec-Bu 4-CF3 4-F CO2Me Me 4-Cl-Ph 4-C1 4-F CO2Me Me 4-Cl-Ph 4-Br 4-F CO2Me Me 4-Cl-Ph 4-OCF3 4-F CO2Me Me 4-Cl-Ph 4-CF3 S-Cl Me Et OCH2CC13 4-CF3 H CO2Me Et NEt2 4-Cl H CO2Me Et NEt2 4-Br H CO2Me Et NEt2 4-OCF3 H CO2Me Et NEt2 .~ 4-CF3 5-Cl CO2Me Et 2,6-di-Me-morpholino :` 4-C1 5-Cl CO2Me Et 2,6-di-Me-morpholino . 4-Br S-Cl CO2Me Et 2,6-di-Me-morpholino .-~ 25 4-OCF3 5-Cl CO2Me Et 2,6-di-Me-morpholino `~:
.~, 4-CF3 5-Cl Me iPr OEt - 4-CF3 H CO2Me iPr OEt 4-Cl H CO2Me iPr OEt -~ 4-Br H CO2Me iPr OEt 4-OCF3 H CO2Me iPr OEt 4-CF3 5-Cl CO2Me iPr OEt --.
. 4-C1 5-Cl CO2Me iPr OEt ; 4-Br 5-Cl CO2Me iPr OEt 4-OCF3 5-Cl CO2Me iPr OEt 4-CF3 5-Br CO2Me iPr OEt 4-C1 5-Br CO2Me iPr OEt -~.
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4-Hr S-Br CO2Me iPr OEt 4-OCF35-Br C02Me iPr OEt 4-CF34-F CO2Me iPr OEt 4-C14-F CO2Me iPr OEt 1~ 4-Br 4-F CO2Me iPr OEt 4-OCF34-F CO2Me iPr OEt 4-CF35-CF3 co2Me iPr OEt 4-CF35-F CO2Me iPr OEt : 4-CF35-Cl Ph iPr OEt - 15 4-CF35-C14-Cl-Ph iPr OEt 4-CF3 S-Cl CO2Et iPr OEt 4-CF35-Cl CO2Me Me ON~(CH3)SCH3 . 4-CF35-Cl CO2Me Me 2,3-dihydro-2,2-dimethylbenzofuranyl ' ~Y-7 ~; 4-CF35-Cl CO2Me Me l-naphthosy : 4-CF35-Cl Me iPr O-n-Bu 4-CF3 ~ CO2Me iPr O-n-Bu . 4-Cl H CO2Me iPr O-n-Bu 4-Br H CO2Me iPr O-n-Bu , 4-OCF3 H CO2Me iPr O-n-Bu 4-CF35-Cl CO2Me iPr O-n-Bu :~. 4-C15-Cl CO2Me iPr O-n-Bu ~' . 4-Br 5-Cl CO2Me iPr O-n-Bu : 30 4-OCF35-Cl CO~Me iPr O-n-Bu 4-CF35-Br CO2Me iPr O-n-Bu.
4-C~ 5-Br CO2Me iPr O-n-Bu 4-Br 5-Br CO2Me iPr O-n-Bu 4-OCF35-Br C2~e iPr O-n-Bu 4-CF34-F CO2Me iPr O-n-Bu ~ 4-C14-F CO2Me iPr O-n-Bu : .
4-Br 4-F CO2Me iPr O-n-Bu ~. . .
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Rl R2 B R8 Rg .
4-OCF3 4-F ~O2Me iPr O-n-Bu 4-CF3 5-CF3 CO2Me iPr ~-n-Bu 4-CF3 5-F CO2Me iPr O-n-Bu 4-CE3 5-Cl Ph iPr O-n-~u 4-CF3 5-C1 4-Cl-Ph iPr O-n-Bu 4-CF3 S-Cl CO2Et iPr O-n-Bu 4-CF3 H CO2Me iPr OCH2CO2Me . 4-CF3 5-Cl CO2Me iPr OCH2CO2Me t 4-CF3 5-Br CO2Me iPr OCH2CO2Me : 15 4-CF3 4-F CO2Me iPr OCH2CO2Me 4-CF3 H CO2Me iPr NMe2 4-Cl H CO2Me iPr NMe2 ~: 4-~r H CO2Me iPr NMe2 4-OCF3 H CO2Me iPr NMe2 ~; 20 4-CF3 5-Cl CO2Me iPr NEt2 4-C1 5-Cl CO2Me iPr NEt2 4-Br 5-Cl CO2Me iPr NEt2 4-OCF3 5-Cl C~2Me iPr NEt2 4-CF3 5-Br CO2Me iPr piperidino :~
4-C1 5-Br CO2Me iPr piperidino . 4-~r 5-Br CO2Me iPr piperidino ~`
4-OCF3 5-~r CO2Me iPr piperidino 4-CF3 4-F CO2Me iPr Et : 4-C1 4-F CO2Me iPr Et 4-Br 4-F CO2Me iPr Et 4-OCF3 4-F CO~Me iPr Et 4-CE3 H H CH2Ph OEt 4-CF3 5-Cl H CH2Ph O-n-octyl 4-CF3 5-Br H CH2Ph OCH2CO2Et 4-CF3 H Me CH2Ph NEt2 ', .
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'` ~ ' ' -' ' . :'` ' ' ' ' ' .,` ' '~ ' ' 2~ 0130 Rl R2 ~ R8 Rg 4-CF3 5-Cl he CH2Ph morpholino 4-CF3 5-Br Me. CH2Ph 4-Cl-Ph : 4-CF3 4-F Me CH2Ph Et 4-CF3 H CO2Me CH2Ph O-n-Bu 4-Cl ~ CO2Me CH2Ph O-iPr 4-Br H CO2Me CH2P~ OCH2CF3 4-OCF3 H CO2Me CH2Ph NMe2 q-CF3 5-Cl CO2Me CH2Ph piperidino 4-C1 5-Cl CO2Me CH2Ph Ph lS 4-Br 5-Cl CO2Me CH2Ph 4-NO2-Ph : 9-OCF3 5-Cl CO2Me CH2Ph ~u 4-CF3 5-Br CO2Me CH2Ph O-n-he~yl ~ 4-C1 5-Br CO2Me CH2Ph O-sec-Bu `: 9-Br S-Br CO2Me CH2Ph OCH2CH20Et :............ 2~ 4-OCF3 5-Br CO2Me CH2Ph NMe2 4-CF3 4-F CO2Me CH2Ph 2,6-di-Me-morpholino 4-C1 4-F CO2Me CH2Ph 3-Br-Ph 4-Br 4-F CO2Me CH2Ph 4-Me-Ph ^ 4-OCF3 4-F CO2Me CH2Ph nPr 4-CF3 5-CF3 CO2Me CH2Ph Me 4-CF3 5-F CO2Me CH2Ph OEt .' 4-CF3 5-Cl Ph CH2Ph O-n-Bu 4-CF3 5-C1 4-Cl-Ph CH2Ph O-n-octyl 4-CF3 5-Cl C02Et CH2Ph OCH2ccl3 -: .:
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l _ R2 B R8 Rg s 9-CF3 H CO2Me Me NMe2 4-Cl H CO2Me Me NMe2 4-Br H CO2Me Me NMe2 4-OCF3 H CO2Me Me NMe2 4-CF3 5-Cl CO2Me Me NMe2 4-C1 5-Cl CO2Me Me NMe2 -:~ 4-Br 5-Cl . CO2Me Me NMe2 4-OCF3 5-Cl CO2Me Me NMe2 ,. 30 4-CF3 5-Br CO2Me Me NMe2 4-C1 5-Hr CO2Me Me NMe2 ;-. 4-Br S-Br CO2Me Me NMe2 ;~ 4-OCF3.5-Br CO2Me Me NMe2 4-CF3 4-F CO2Me Me NMe2 ;. 35 4-C1 4-F CO2Me Me NMe2 . ., , ~ .
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2'~QQ130 : - 57 Rl R2 E~ R8 Rg 5 .
4-~r 4-F CO2Me Me NMe2 4-OCF3 4-F CO2Me Me NMe2 4-CF3 5-CF3 CO2Me Me NMe2 4-C~3 5-F CO2Me Me NMe2 : 104-CF3 5-Cl Ph Me NMe2 ~:. 4-CF3 5-C1 4-Cl-Ph Me NMe2 4-CF3 5-Cl CO2Et Me NMe2 : 9-CF3 H CO2Me Me NEt2 -~ 4-Cl H CO2Me Me NEt2 !~:-15 9-Br H CO2Me Me NEt2 4-OCF3 H CO2Me Me NEt2 -CF3 5-Cl CO2Me Me NEt2 4-C1 5-Cl CO2Me Me NEt2 4-Br 5-Cl CO2Me Me NEt2 204-OCF3 5-Cl CO2Me Me NEt2 4-CF3 5-8r CO2Me Me NEt2 4-C1 5-Br CO2Me Me NEt2 - 4-Br 5-Br CO2Me Me NEt2 4-OCF3 5-Br CO2Me Me NEt2 4-CF3 4-F CO2Me Me NEt2 :~, 4-C1 4-F CO2Me Me piperidino . 4-BI 4-F CO2Me Me piperidino ;. 4-OCF3 4-F CO2Me Me piperidino .. 4-CF3 5-CF3 CO2Me Me piperidino . 304-CF3 5-F CO2Me Me piperidino 4-CF3 5-Cl Ph Me piperidino . 4-CF3 !5-C1 4-Cl-Ph Me piperidino 4-CF3 S-Cl CO2Et Me piperidino 4-CF3 H CO2Me Me C2H5 354-CF3 5-Cl CO2Me Me C2H5 ~ ~::
:. 4-CF3 5-Br CO2Me Me C2H5 ~ s.:
4-CF3 4-F CO2Me Me C2H5 ;
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Rl R2 ~ R8 Rg 4-CP3 H CO2Me Me n-hexyl 4-Cl H CO2Me Me n-he~yl 4-Br H C02Me Me n-he~yl 4-OCF3 H CO2Me Me n-he~
4-CF3 5-Cl CO2Me Me Ph 4-C1 5-Cl CO2Me Me Ph 4-Br S-Cl CO2Me Me Ph 4-OCF3 5-Cl CO2Me Me Ph 4-CF3 5-Br CO2Me Me 4-Cl-Ph 4-C1 5-Br CO2Me Me 4-Cl-Ph 4-Br 5-Br CO2Me Me 4-Cl-Ph 4-OCF3 5-Br CO2Me Me 4-Cl-Ph 4-CP3 9-F CO2Me Me 4-Me-Ph ;~ 4-C1 4-F CO2Me Me 4-Me-Ph ;:
. 20 4-Br 4-F CO2Me Me 4-Me-Ph 4-OCF3 4-F CO2Me Me 4-Me-Ph 4-CF3 5-CF3 CO2Me Me n-Bu 4-CF3 5-F CO2Me Me n-Bu ` 4-CF3 5-Cl Ph Me n-Bu " . 25 4-CF3 5-C1 4-Cl-Ph Me n-13u 4-CE3 5-Cl CO2Et Me n-Bu . 4-CF3 H H Et NMe2 ., 4-CF3 5-Cl H Et NMe2 4-CF3 5-Br H Et NMe2 3~ 4-CF3 4-F H Et NMe2 . 4-CF3 H Me Et NEt2 4-CF3 5-Cl Ne Et NEt2 .` 4-CF3 5-Br Me Et NEt2 4-CF3 4-F Me Et NEt2 . 35 4-CF3 5-Cl CO2Me Et morpholino 4-C1 5-Cl CO2Me Et morpholino 4-Br 5-Cl CO2Me Et morpholino 4-OCF3 5-C1 ~02Me Et morpholino . .
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9-CF35-Cl CO2Me Et iPr 4-C1 5-Cl CO2Me Et iPr 4-Br 5-Cl CO2Me Et iPr 4-OCF3 5-Cl CO2Me Et iPr 10 4-CF3 5-ESr CO2Me Et n-Bu 4-C1 5-~r CO2Me Et n-Bu 4-Br 5-Br CO2Me Et n-Bu ~4-OCF3 5-Br CO2Me Et n-~u 4-CF3 4-F CO2Me Et Ph . 15 4-C1 4-F CO2Me Et Ph - 4-Br 4-F CO2Me Et Ph 4-OCF3 4-F CO2Me Et Ph 4-CF3 H CO2Me i Pr NMe2 4-Cl H CO2Me iPr NMe2 20 4-Br H CO2Me iPr NMe2 4-OCF3 H CO2Me i Pr NMe2 4-CF3 5-Cl CO2Me iPr NMe2 ` 4-C1 5-Cl CO2Me iPr NMe2 1~ 4-Br 5-Cl CO2Me iPr NMe2 -` 25 4-OCF3 5-Cl CO2Me iPr NMe2 -~ 4-CF3 5-Br CO2Me iPr NMe2 4-C1 5-Br CO2Me iPr NMe2 ' 4-Br 5-Br CO2Me iPr NMe2 ' . 4-OCF3 5-Br CO2Me iPr NMe2 - 30 4-C~3 4-F CO2Me iPr NMe2 4-C1 4-F CO2Me iPr NMe2 4-Br 4-F CO2Me iPr NMe2 ; 4-OCF3 4-F CO2Me iPr NMe2 4-CF3 5-CF3 C2 iPr NMe2 ' 35 4-CF3 5-F C2M~ iPr NMe2 4-CF3 5-Cl Ph iPr NMe2 4-CF3 5-C1 4-Cl-Ph iPr NMe2 4-CF3 5-Cl CO2Et iPr NMe2 '~',, ;
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Z'~Q~130 . Rl R2 B RB Rg :' . , : 4-CF3 H ~O2Me iPr 2,6-di-Me-morpholino 4-CF3 5-Cl CO2Me iPr 2,6-di-Me-m~rpholino 4-CF3 5-Br CO2Me iPr 2,6-di-Me-morpholino 4-CF3 4-F CO2Me iPr 2,6-di-Me-morpholino 4-CF3 H CO2Me iPr piperidino : 4-OCF3 H CO2Me iPr piperidino 4-CF3 5-Cl CO2Me iPr Et 4-C1 5-Cl CO2Me iPr Et 4-Br 5-Cl CO2Me iPr Et : 15 4-OCF3 5-Cl CO2Me iPr Et q-CF3 5-Br CO2Me iPr n-Bu ;.~ 4-C1 5-Br CO2Me iPr n-Bu : 4-Br 5-Br CO2Me iPr n-Bu 4-OCF3 5-Br CO2Me iPr n-Bu ; 20 4-CF3 4-F CO2Me iPr Ph .~~ .
'. 4-C1 4-F CO2Me iPr Ph 4-Br 4-F CO2Me iPr Ph ~: 4-OCF3 4-F CO2Me iPr Ph -~ 4-CF3 5-CF3 CO2Me iPr 4-Cl-Ph . 25 4-CF3 5-F CO2Me iPr 4-Cl-Ph 4-CF3 5-Cl Ph iPr 4-Cl-Ph '~ 4-CF3 5-C1 4-Cl-Ph iPr 4-Cl-Ph -~
4-CF3 5-Cl C~2Et iPr 4-Cl-Ph .
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4-CF3 H CO2Me tBu S OEt OEt 4-Cl H CO2Me t~u S OEt OEt 4-Br H CO2Me tBu S OEt OEt 4-OCF3 H CO2Me tBu S OEt OEt 4-CF3 S-Cl CO2Me tBu S OEt OEt `~; 4-Cl S-Cl CO2Me tBu S OEt OEt 4-Br S-Cl CO2Me tBu S OEt OEt ., 4-OCF3 5-Cl CO2Me tBu S OEt OEt ` 4-CF3 S-Br CO2Me tBu S OEt OEt ~; 4-C1 5-Br CO2Me tBu S OEt OEt 4-Br 5-Br CO~Me tBu S OEt OEt 4-OCF3 S-Br CO2Me tBu S OEt OEt 4-CF3 4-F CO2Me tBu S OEt OEt 4-C1 4-F CO2Me tBu S ~ OEt OEt 9-Br 4-F CO2Me tBu S OEt OEt ~` 4-OCF3 4-F CO2Me tBu S OEt . OEt 4-CF3 5-CF3 CO2Me tBu S OEt OEt 4-CF3 5-F CO2Me tBu S OEt OEt 4-CF3 S-Cl Ph tBu S OEt OEt .,' ~.
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z~l t~30 Rl R2 B R8 Y' Y Rlo Y Rll 4-CF3 5-C1 4-Cl-Ph tBu S O~t OEt 4-CF3 5-C1 ~2Et tHu ~ OEt OEt 4-CF3 H CO2Me tBu S OCH2C(Me)2CH~O
10 4-Cl H CO2Me tBu S OCH2C(Me)2CH2o 4-Br H CO2Me tBu S OCH2C(Me)2CH20 4-OCF3 H C02Me tBu S OCH2C(Me)2CH20 : 4-CF3 5-Cl CO2Me t8u S OCH2C(Me)2CH20 4-C1 5-Cl CO2Me tBu S OCH2C(Me)2cH2o 15 4-Br 5-Cl CO~Me tBu S OCH2c(Me)2cH20 4-OCF3 5-Cl CO2Me tBu S OCH2C(Me~2CH20 4-CF3 5-Br CO2Me tBu S OCH2C(Me)2CH20 4-C1 5-Br CO2Me tBu S OCH2c~Me)2cH20 4-Br 5-Br CO2Me tBu S OCH2c(Me~2cH20 2~ 4-OCF3 5-Br CO2Me tBu S OCH2c~Me)2c~20 : 4-CF3 4-F CO2Me tBu S OCH2C(Me)2cH2o 9-C1 4-F CO2Me tBu S OCH2C~Me)2c~20 4-Br 4-F CO2Me tBu S OCH2C~Me)2CH20 4-OCF3 4-~ CO2Me tBu S OCH2C~Me)2CH20 25 ~-CF3 5-CF3 CO2Me tBu S OCH2c(Me)2cH20 4-CF3 5-F ~2Me t~u S OCH2c(Me)2cH20 i 4-CF3 5-Cl Ph tBu S OCH2C(Me)2cH2o 4-CF3 5-C1 4-Cl-Ph t9u S OCH2c(Me~2cH20 4-CF3 5-Cl CO2Et tBu S OCH2c(Me)2cH20 30 4-CF3 H CO2Me tBu S OCH2CH2CH20 4-C~ ~ C2~e tBu S OCH2CH2CH20 4-Br H CO2Me tBu S OCH2CH2CH20 4-OCF3 H CO2Me t~u S OCH2CH2CH20 4-CP~ 5-Cl CO2Me t~u S OCH2CH2CH20 35 4-Cl S-Cl CO2Me tBu S OCH2CH2CH20 4-Br 5-Cl CO2Me tBu S OCH2CH2CH20 4-OCF3 5-Cl CO2Me tBu S CH2CH2CH20 ~ ' ' ~, .
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5 1 R2 B R~ Y' Y'Rlo Y Rll 4-CF3 5-Br CO2Me tBu S OcH2cH2cH2o 4-C1 5-Br CO2Me tBu S OCH2CH2CH2o 4-Br 5-Br CO2Me tBu S OCH2CH2CH2O - ~.
4-OCF3 5-Br CO2Me tBu S OcH2cH2cH2o .
4-CF3 4-F CO2Me tBu S OCH2CH2CH2O . .
4-C1 4-F CO2Me t~u ~ OCH2CH2CH2 ~ .
4-Br 4-F CO2Me tBu S OCH2CH2CH2 4-OCF3 4-F CO2Me tBu S OCH2CH2CH2O
4-CF3 5-CF3 CO2Me tBu OCH2CH2CH2 4-CF3 5-F CO2Me tBu S OCH2CH2CH2O :.
4-CF3 S-Cl Ph tBu S OCH2CH2CH2 4-CF3 5-C1 4-Cl-Ph tBu S OCH2cH2cH2O
4-CF3 5-Cl CO2Et tBu S OCH2CH2CH2O .
4-CF3 H CO2Me tBu S OCHzCH2O
4-Cl H CO2Me tBu S OCH2CH2O
4-Br H CO2Me tBu S OCH2CH2 4-OCF3 H CO2Me tBu S OCH2CH2O .
; 4-CF3 5-Cl CO2Me tBu S OCH2CH2 ~- 254-C1 5-Cl CO2Me tBu S OCH2CH2O :;
9-Br S-Cl CO2Me tBu S OCH2CH2O
4-OCF3 5-Cl CO2Me tBu S OCH2CH2O '.
4-CF3 5-~r CO2Me tBu S OCH2CH2O
, 4-C1 5-Br CO2Me tBu S OCH2CH2O . .
- 304-Br 5-Br CO2Me tBu S OCH2CH2O .~
4-OCF3 5-Br CO2Me tBu S OCH2CH2O ::
4-CF3 4-F CO2Me tBu S OCH2CH2O
4-C1 4-F CO2Me tBu S OCH2CH2 4-Br 4-F CO2Me tBu S OCH2CH2 4-OCF3 4-F CO2Me tBu S OCH2CH2O
. 4-CF3 5-CF3 CO2Me tBu S OCH2CH2 4-CF3 5-F CO2Me tBu S OCH2CH2O
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4-CF3 5-Cl Ph tBu S Q2CH2O
4-CF3 S-Cl 4-Cl-Ph tBu S ~H2C~2 4-CP3 5-Cl CO2Et tBu S CH2cH2 4-CF3 H CO2Me iPr S OEt OEt :~ 4-Cl H CO2Me . iPr ~ OEt OEt 4-Br H CO2Me iPr S OEt OEt 4-OCF3 H ~O2Me iPr S OEt OEt 4-CF3 5-Cl CO2Me iPr S OEt OEt ~ lS 4-C1 5-Cl CO2Me iPr S OEt OEt - 4-Br 5-Cl CO2Me iPr S OEt OEt 4-OCF3 S-Cl CO2Me iPr S OEt OEt 4-CF3 5-~r CO2Me iPr S OEt OEt 4-Cl S-Br CO2Me iPr S OEt OEt 4-Br 5-Br CO2Me iPr S O~t OEt :~ 4-OCF3 5-Br CO2Me iPr S OEt OEt 4-CF3 4-F CO2Me iPr S OEt OEt , . . .
4-C1 4-F CO2Me iPr S OEt OEt ~ 9-Br 4-F CO2Me iPr S OEt OEt ; 25 4-OCF3 4-F CO2Me iPr S OEt OEt.
4-CF3 5-CF3 CO2Me iPr S OEt OEt 4-CF3 S-F CO2Me iPr S OEt OEt 4-CF3 5-Cl Ph iPr S OEt OEt 9-CF3 5-C1 4-CI-Ph iPr S OEt OEt 3C 4-CF3 5-Cl CO2Et iPr S OEt OEt 4-CF3 H CO2Me iPr S OCH2c~Me~2cH2 4-Cl H CO2Me iPr S OCH2C~Me)2cH2O
4-Rr H CO2Me iPr S OCH2C(Me)2cH2O
4-OCF3 H .C02Me iPr S OcH2c(Me)2cH2o 4-CF3 S-Cl CO2Me iPr S OcH2c(Me)2c~2o 4-C1 5-Cl CO2Me iPr S OCH2c(Me)2cH2O
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4-Br 5-Cl CO2Me iPr 5 OcH2c(Me)2cH2o 4-OCF3 5-Cl CO2Me iPr S OCH2C(Me)2CH2o 4-CF3 5-Br CO2Me iPr S OCH2c(Me)2cH2O
4-C1 5-Br CO2Me iPr S OCH2C(Me)2CH2O
4-~r 5-Hr CO2Me iPr S OCH2C(Me)2CH2O
4-OCF3 5-Qr CO2Me iPr S OCHzC(Me)2CH2O
4-CF3 4-F CO2Me iPr S OCH2C(Me)2cH2o 4-C1 4-F CO2Me iPr S OCH2C(Me)2cH2o ; 15 4-~r 4-F CO2Me iPr S OCH2C(Me)2CH2O
4-OCF3 4-F CO2Me iPr S OCH2C(Me)2CH2O
4-CF3 S-CF3 CO2Me iPr S OCH2C(Me)2CH2O
4-CF3 5-F CO2Me iPr S OCH2C(Me)2CH2O ..
4-CF3 5-Cl Ph iPr S OCH2c(Me)2cH2O
~. 20 4-CF3 5-C1 4--Cl-Ph iPr S OCH2C(Me)2CH2O
:~ 4-CF3 5-Cl CO2Et iPr S OCH2CtMe)2CH2O ~-4-CF3 H CO2Me Me S OEt OEt 4-Cl H CO2Me Me S OEt OEt .. 4-Br H CO2Me Me S OEt OEt '?`: 25 4-OCF3 H CO2Me Me S OEt OEt 4-CF3 5-Cl CO2Me Me æ OEt OEt .. 4-C1 5-Cl CO2Me Me S OEt OEt ~ 4-Br 5-Cl CO2Me Me S OEt OEt ,'~ . 4-OCF3 5-Cl CO2Me Me S OEt OEt -: 30 4-CF3 5-Br CO2Me Me S OEt OEt : 4-C1 5-Br CO2Me Me S . OEt OEt ;.
4-Br 5-Br CO2Me Me S OEt OEt `
4-OCF3 5-Br C02Me Me S OEt OEt 4-CF3 4-F CO2Me Me S OEtOEt . ~:
:~- 35 4-C1 4-F CO2Me Me S OEt OEt 4-Br 4-F CO2Me Me S OEt OEt :
4-OCF3 4-F CO2Me Me S OEt OEt 4-CF3 5-CF3 co2Me Me S OE:tOEt ` .
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4-CF35-F CO2Me Me S OEt OEt 4-CF3 S-Cl Ph Me S OEt OEt 4-CF35-C14-Cl-Ph Me S OEt OEt 4-CF3 H CO2Me tBu o OEt OEt 4-Cl H CO2Me tBu O OEt OEt q-Br H CO2Me tBu O OEt OEt ; 4-OCF3 H CO2Me tBu O OEt OEt .
4-CF35-Cl C02Me tBu O OEt OEt 4-C15-Cl CO2Me tBu O OEt OEt ; 4-Br S-Cl CO2Me tBu O OEt OEt g-OCF35-Cl CO2Me tBu O OEt OEt 4-CF35-Br CO2Me tBu O OEt OEt 4-C15-Br CO2Me tBu O OEt OEt 4-Br 5-Br CO2Me tBu O OEt OEt 4-OCF35-Br CO2Me tBu o OEt OEt 4-CF34-F CO2Me tBu O OEt OEt 4-C14-F CO2Me tBu O OEt OEt . 4-Br 4-F C02Me tBu O OEt OEt 4-OC~34-~ CO2Me $Bu O OEt OEt 4-CF35-CF3 CO~Me tBu O OEt OEt 4-CF35-F CO2Me tBu O OEt OEt 4-C~3 ~-Cl Ph tBu O OEt OEt 4-CF35-C14-Cl-Ph tBu O OEt OEt -~
4-CF35-Cl C~2Et tBu O OEt OEt 4-CF3 H CO2Me tBu O OCH2C~Me)2CH2~
; 4-CI H CO2Me tBu O OCH2C~Me)2CH20 :
~, 4-Br ~ CO2Me tBu O OCH2C(Me)2 Q2 4-OCF3 H CO2Me tBu O ocH2c(Me)2Q2o 4-CF35-Cl CO2Me tBu o OCH2C~Me)2cH2O
~ 4-Cl S-Cl C02Me tBu o OCH2C(Me)2cH2O
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9-Br 5-Cl CO2Me tBu ~ OCH2C(Me~2CH20 - 4-OCF3 5-Cl CO2Me tBu O OCH2CtMe)2CH2o 4-CF3 5-Br CO2Me tBu O OCH2C(Me)2CH2O
: 10 4-C1 5-Br CO2Me tBu O OCH2C(Me)2CH2O
4-Br 5-Br CO2Me tBu O OCH2C(Me)2CH2O
4-OCF3 S-Br CO2Me tBu O OCH2C(Me)2CH2O
: 9-CF3 4-F CO2Me tBu O OCH2C(Me)2cH2o 4-C1 4-F CO2Me tBu O OCH2C(Me)2CH2O
9-Br 4-F CO2Me tBu O OCH2C(Me)2cH2o 4-OCF3 4-F CO2Me tBu O OCHzC(Me)zCH2O
4-CF3 5-CF3 CO2Me tBu O OCH2C(Me)2cH2o : 4-CF3 5-F CO2Me tBu O OCH2C(Me)2cH2o . 4-CF3 5-Cl Ph tBu O OCH2C(Me)2CH2O
4-CF3 5-C1 4-Cl-Ph tBu O OCH2C(Me)2cH2o ,~ 4-CF3 5-Cl CO2Et tBu O OCH2C(Me)2cH2o 'J ~,;
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4-C1 4-F CO2Me iPr O Et OEt 4-Br 4-F CO2Me iPr O Et OEt 4-OCF3 4-F CO2Me iPr O Et OEt 4-CF3 5-CF3 CO2Me iPr O Et OEt 4-CF3 S-~ CO2Me iPr O Et OEt ~ 4-CF3 5-Cl Ph iPr O Et . OEt ; 4-CF3 5-C1 4-Cl-Ph iPr O Et OEt 4-CF3 5-Cl CO2Et iPr O Et OEt 4-CF3 H CO2Me iPr O Et O-iPr : 15 4-Cl H CO2Me iPr O Et O-iPr :
"` 4-~r H CO2Me iPr O Et O-iPr .. 4-OCF3 H CO2Me iPr O Et O-iPr . 4-CF3 5-Cl CO2Me iPr O Et O-iPr 4-Cl S-Cl CO2Me iPr O Et O-iPr :
`:- 4-Br 5-Cl CO2Me iPr O Et o-iPr 4-OCF3 5-Cl CO2Me iPr O Et O-iPr :~
` 4-CF3 5-Br CO2Me iPr O Et O-iPr `~ 4-C1 5-Br CO2Me iPr O Et O-iPr .`~ 4-8r 5-8r CO2Me iPr O Et O-iPr 25 9-OCF3 5-Br CO2Me iPr O Et o-iPr - 4-CF3 4-F CO2Me iPr O Et O-iPr 4-C1 4-F CO2Me iPr O Et O-iPr 4-Br 4-F CO2Me iPr O Et O-iPr 4-OCF3 4-F CO2Me iPr O Et O-iPr . 30 4-CF3 5-CF3 CO2Me iPr O Et o-iPr . 4-CF3 5-F C2M~ iPr O Et O-iPr 4-CF3 5-Cl Ph iPr O Et O-iPr 4-CF3 S-Cl 4-Cl-Ph iPr O Et O-iPr 4-CF3 S-Cl CO2Et iPr O Et O-iPr 35 4-CF3 H CO2Me iPr O Et OPh 4-Cl H CO2Me iPr O Et OPh ~" .
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4-Br H CO2Me iPr O Et . OPh 4-OCF~ H C02Me iPr O Et OPh 4-CF3 5-Cl CO2Me iPr O Et OPh 4-C1 5-Cl CO2Me iPr O Et OPh 4-Br 5-Cl CO2Me iPr O Et OPh 4-OCF3 5-Cl CO2Me iPr O Et OPh 4-CF3 S-~r CO2Me iPr O Et OPh 4-Cl S-Br CO2Me iPr O Et OPh 4-Br 5-Br CO2Me iPr O Et OPh 4-OCF3 5-Br CO2Me iPr O Et OPh 4-CF3 4~~ CO2Me iPr O Et OPh 4-C1 4-F CO2Me iPr O Et OPh ~-~ 9-Br 4-F CO2Me iPr O Et OPh 4-OCF3 4-F CO2Me iPr O Et OPh 4-CF3 5-CF3 CO2Me iPr O Et OPh . 4-CF3 S-P CO2Me iPr O Et OPh 4-CF3 5-Cl Ph iPr O Et OPh 4-CF3 5-C1 4-Cl-Ph iPr O Et OPh 4-CF3 5-Cl CO2Et iPr O Et OPh . 2~ 4-Br 4-F CO2Me iPr O Ph OEt 4-OCF3 4-F CO2Me iPr O Ph OEt ~` 4-CF3 5-CF3 CO2Me iPr O Ph OEt 4-CF3 5-F CO2Me iPr O Ph OEt 4-CF3 5-Cl Ph iPr O Ph OEt 4-C~3 S-Cl 4-Cl-Ph iPr O Ph OEt 4-CF3 5-Cl CO2Et iPr O Ph OEt ~ 4-CF3 H CO2Me tBu O Et OEt : 4-Cl H CO2Me tBu O Et OEt 4-Br H CO2Me tBu O Et OEt 4-OCF3 H CO2Me tBu O Et OEt 4-CF3 5-Cl C~2Me tBu O Et OEt 4-C1 5-Cl CO2Me tBu O Et OEt ., ' ~''~'~
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21~ ~0'~30 ` R R2 B R8 Y' Rlo Y Rll 9-Br 5-Cl CO2Me tBu O Et OEt 4-OCF3 5-Cl CO2Me tBu O Et OEt 4-CF3 5-Br CO2Me tBu O Et OEt ::: 4-Cl S-E~r C02Me tBu O Et OEt 4-Bs 5-Br COzMe tBu O Et OEt 4-OCF3 5-Br C02Me tE~u O Et OEt 4-CF3 4-F CO2Me tBu O Et OEt 4-C1 4-F C02Me tBu O Et OEt 4-E~r 9-F C02Me tBu O Et OEt :~ 15 4-OCF3 4-F CO2Me tBu O Et OEt 4-CF3 5-CF3 CO2Me tBu O Et OEt 4-CF3 5-F CO2Me tBu O Et OEt 9-CF3 5-Cl Ph tBu O Et OEt 4-CF3 5-C1 4-Cl-Ph tBu O Et OEt 20 4-CF3 5-Cl CO2Et tBu O Et OEt 4-CF3 H CO2Me tBu O Et O-iPr 4-Cl H CO2Me tBu O Et O-iPr . 4-Br H CO2Me tBu O Et O-iPr ; 4-OCF3 H CO2Me tBu O Et O-iPr 25 4-CF3 5-C1 CO2Me tBu O Et O-iPr 4-C1 5-Cl CO2Me tBu O Et O-iPr 4-Br 5-Cl CO2Me tBu O Et O-iPr 4-OCF3 5-Cl CO2Me tBu O Et O-iPr 4-CF3 5-Br CO2Me tBu O Et O-iPr 5-Br CO2Me tBu O Et O-iPr . 4-Br 5-Br CO2Me tBu O Et O-iPr 4-OCF3 5-Br CO2Me tBu O Et O-iPr 4-CF3 4-F CO2Me tBu O Et O-iPr 4-C1 4-F CO2Me tBu O Et O-iPr .` 35 4 Br 4-F CO2Me tBu O Et O-i~r - 4-OCF3 4-F C02Me tE~u O Et O-iPr 4-CF3 5-CF3 CO2Me tBu O Et O-iPr 4-CF3 5-F CO2Me tBu O Et O-iPr ., .''. .
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24~00130 . Rl R2 BR& Y' Rlo Y Rll .__ 4-CF3 5-Cl Ph t~u O Et O-iPr 9-CF3 5-C1 4-Cl-Ph tBu O Et O-iPr 4-CF3 5-Cl CO2Et tBu O Et O-iPr 4-CF3 H CO2Me tBu S Et OPh 4-Cl H CO2Me tBu S Ph OEt : 4-Br H CO2Me tBu S Ph O-iPr 4-OCF3 H CO2Me tBu S Ph OPh 4-Br 5-Br CO2Me iPr S iPr OEt 4-OCF3 5-Br CO2Me iPr S iPr O-iPr 4-CF3 4-F CO2Me iPr S iPr OPh 4-Cl 9-F CO2Me iPr S nPr OEt 4-Br 4-F CO2Me iPr S nPr O-iPr 4-OCF3 4-F CO2Me iPr S nPr OPh . 4-CF3 5-CF3 CO2Me tBu S Me OEt 4-CF3 5-F CO2Me tBu S Me O-iPr 4-CF3 5-Cl Ph t9u S Me OPh 4-CF3 5-C1 4-Cl-Ph tBu S Me O-sec-Bu 4-CF3 5-Cl CO2Et tBu S Me O-nPr .
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4-8r 5-8r CO~Me Et Et 4-OCF3 5-Br CO2Me Et Et 4-F C~2Me Et Et . ~ , .
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Rl R2 El Rlo Rll 4-C1 4-F CO2Me Et Et 4-Br 4-F CO2Me Et Et 4-OCF3 4-F CO2Me ~t ~t 4-CF3 5-CF3 C2Me Et ~t q-CF3 5-~ CO2Me Et ~t J-CF3 5-Cl Ph Et ~t 4-CF3 5-Cl q-Cl-Ph ~t Et ~ 4-CF3 5-CI CO2Et Et Et : 4-CF3 5-Cl Ph Ph Ph .. 15 4-CF3 5-C1 4-Cl-Ph Ph Ph 4-CF3 5-Cl C2Et Ph Ph :
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~: 20 .` Rl R2 B R~ R12 . _ ~ 4-CF3 ~ CO2Me nBu nBu '~ 4-Cl H CO2Me nBu nBu :~ . 25 4-Br H CO2Me nBu nBu 4-OCF3 H CO2Me nBu nBu . 4-CF3 5-CI CO2Me nBu nBu . 4-C1 5-Cl CO2Me nBu DBu ..
4-Br 5-Cl CO2Me nBu nBu ~` 30 4-OCF3 5-CI CO2Me nBu nBu .
~ 4-CF3 5-Br C02Me nBu ~Bu ,~ 4-C1 5-Br CO2Me nBu ~8u 4-Br 5-Br C02Me ~9u n8u 4-OCF3 5-Br C2~e nBu nBu . 35 4-CF3 4-F CO2Me nBu nBu -'; ' ' ~' ~
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2~001 30 Rl R2 ~ R8 R12 5 .
4-C1 4-F CO2MenBu DBu 4-Br 4-F CO2MeD~U DBU
4-OCF3 4-F CO2MenBu nBu 4-CF3 5-CF3 CO2Me nBu nBu 4 CF3 5-F CO2Me DBU nBu 4-CF3 5-Cl Ph nBu DBu 4-CF3 5-Cl q-Cl-Ph ~Bu DBu 4-CF3 5-Cl C02EtD}IU ~Bu . 4-CF3 H CO2Me-CH2CH2C~2cH2cH2-.:. 15 4-Cl H CO2Me-CH2CH2CH2cH2cH2-4-Br H CO2Me-CH2CH2CH2cH2cH2-4-OCF3 H C02Me-CH2CH2C~2cH2cH2-: 4-CF3 5-Cl CO2Me-CH2CH2CH2cH2cH2-4-C1 5-Cl CO2Me-CH2CH2CH2cH2cH2 .: 2 0 4-Br 5-Cl CO2Me-CH2CH2CH2cH2cH2-. 4-OCF3 5-Cl CO2Me-CH2CH2CH2cH2cH2-4-CF3 5-Br CO2Me-CH2CH2CH2cH2cH2-4-C1 5-Br C02Me-CH2CH2CB2cH2cH2-4-Br 5-Br CO2Me-CH2CN2CH2CH2CH2-.t 2 5 4 OCF3 5-BrCO2Me -CH2CH2CH2c~2cH2-4-CF3 4-F CO2Me-CH2CH2CH2cH2cH2-4-C1 4-F CO2Me-CH2CH2CH2CH2CH2-4-Br 4-F CO2MeCH2CH2CH2C~32cH2-4-OCF3 4-F CO2Me-CH2CH2CH2CH2CN2_ CF3 S-CF3 CO2Me -CH2CH2CN2cH2cH2-4-CF3 5-F CO2Me-CH2CH2CH2cH2cH2 ,~ 4-CF3 5-Cl Ph-CH2CH2CH2CH2~H2 4 CF3 S-Cl -CI-Ph -CH2CH2CH2CH2CH2-4-CF3 5-Cl C02Et -CH2CH2CH2cH2cH2-3 5 4-CF3 H C02Me-CH2CH20CH2cH2-4-Cl H C02Me-CN2CHZOcH2cH2-.
4-~r H C02Me-CN2CH20C~2cN2-.
, ' `' Z;l~f~0130 :
~1 R2 B R8 R12- ---4-OCF3 H CO2Me -CH2CH2~CH2CH2-q C~3 5-Cl CO2Me -CH2CH2OCH2CH2-4-C1 5-Cl CO2Me -CH2CH2OCH2CH2_ 4-Br 5-Cl CO2Me -CH2cH2OcH2cH2 4-OCF3 5-Cl CO2Me -CH2cH2OcH2cH2-4-CF3 5-Br CO2Me -CH2CH2~CH2cH2-4-C1 5-Br CO2Me -CH2cH2OcH2cH2 4-Br 5-Br CO2Me _CH2cH2OcH2cH2 4-OCF3 5-Br CO2Me -CH2cH2OcH2cH2 4-CF3 4-F CO2Me -CH2cH2OcH2cH2-4-C1 4-F CO2Me -CH2CH2OCH2CH2-4-Br 4-F CO2Me -CH2cH2OcH2cH2-4-OCF3 4-F CO2Me -CH2CH2OCH2CHz-4-CF3 5-CF3 CO2Me -CH2cH2OcH2cH2-`; 20 4-CF3 5-F CO2Me -CH2CH2OCH2CH2_ 4-CF3 5-Cl Ph -CH2cH2OcH2cH2 ~:. 4-CF3 5-C1 4-Cl-Ph -CH2CH2OCH2CH2-4-CF3 5-Cl CO2Et -CHzCH2OCH2CH2_ ;
~.i q-CF3 H CO2Me -CH2CHMeOCHMeCH2-:` 25 4-Cl H CO2Me -CH2CHMeOCHMeCN2-. 4-~3r H CO2Me -CH2CHMeOCHMeCH2-.. 4-OCF3 H CO2Me -CH2CHMeOCHMeCH2- ~ -~: 4-C~3 S-C~ C~2Me -CH2CHMeOCNMeCH2-.~ 4-C1 5-CI CO2Me -C~2CNMeOCHMeCH2_ :~ 30 4-Br 5-Cl CO2Me -CN2CHMeOCHMeCH2-~ 4-OCF3 5-Cl CO2Me -CH2CKMeOCHMeCH2_ .~ 4-CF3 5-Br C02Me -CH2CHMeOCHMeCH2-q-Cl 5-Br CO2Me -CN2CHMeOCNMeCN2_ 4-Br 5-Br C02Me -CH2C~MeOCHMeCH2-4-OCF3 5-Br CO2Me -CH2CHMeOCHMeCH2_ ~ ç-cr3 4-r C~2M~ -CNzCNMeOCNMoCNz-.. .. .
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4-C1 4-F C02~e -CH2CHMe~CHMeCH2-4-~r 4-F CO2Me -CH2C~M~OCHMeCH2_ 4-OCF3 4-F C02Me -CH2CHMeOCHMeCH2-~-CF3 5-CF3 C02Me -CH2CHMeOC~MeCH2-4 CF3 5-F CO2Me -CH2CHMeOCHMeCH2- !`
4-CF3 5-Cl Ph -C~2CHMeOCHMeCH2 4-CF3 5-Cl 4-CI-Ph -CH2C~MeOCHMeCH2-4-CF3 5-Cl CO2~t -CH2CHMeOCHMeCH2-4-CF3 H CO2Me Et cyClo-c6Hll 4-CI H CO2Me Et cyclo-C6Hli -Br H CO2Me Et cyclo-c6 4-OCF3 H CO2Me Et cyclo-C6H
4-C~3 5-Cl CO2Me Et cyclo-C
4-C1 5-Cl CO2Me Et CYC1~
^, 20 4-9r 5-Cl CD2Me Et cyclo-~6 ;`' 4-OCF3 5-Cl CO2Me Et CYC1-4-CF3 5-Br CO2Me Et cyclo-C
4-Cl S-Br CO2Me Et cyclo-C
4-Br 5-Br CO2Me Et cyclo-C6B
4-OCF3 5-9r CO2Me Et cyclo-c6Hll ~, 4-CF3 4-F CO2Me Et cyclo-C6Hll :
-~ 4-C1 4-~ CO2Me Et cyclo-C6H
;~ 4-Br 4-F CO2Me Et CYC1~
~-OCr3 4-F CO2Me Et cyclo-C6H
4-CF3 5-CF3 CO2Me Et cyclo-C6H
4-CF3 5~~ CO2Me Et cyCl~-c6H
~ 4-CF3 S-Cl Ph Et cyclo-C6H
:: 4-CF3 5-C1 4-Cl-Ph Et ~YCl~c6Hll. ' ~- 4-CF3 5-Cl CO2Et Et CYel~C6Nll ~ .
4-CF3 H CO2Me iPr CH2CH2CO2Et 4-Cl H CO2Me iPr CN2CH2C02Et "
4-Br H CO2Me iPr CH2CH2C2~t . . ~'-,.
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- . Rl R2B ~8 R12 4-OCF3 HCO2Me iPr CN2CH2C2Et : ~-C~3 S-Cl CO2Me ~Pr C~2CH2C2Et 4-C1 5-Cl CO2Me iPr CH2CH2~2Et 4-~r 5-Cl CO2Me lPr CH2CH2C2~t 4-OCF3 5-Cl CO2Me iP~ . CH2CH2C2Et 4-CF3 5-Br CO2Me iPr CH2 Q2C2Et ;~ 4-C1 5-Br CO2Me ~Pr CH2CH2C2Et 4-~r S-Br CO2Me iPr Q2CH2CO2Et 4-OCF3 5-Br CO2Me iPr CH2CH2CO2Et ~: 15 4-CF3 4-FCO2Me iPr Q2CH2CO2Et 4-C1 4-FCO2Me iPr CH2CH2C02Et 4-Br q-FCO2Me iPr CH2CH2C2Et ; 4-OCF3 4-FCO2Me iPr Q2CH2CO2Et 4-CF3 5-CF3 CO2Me iPr CH2CH2C2Et q-CF3 S-~CO2Me iPr CH2C~2C2Et .;~ 4-CE3 5-Cl Ph iPr CH2CH2C2Et .~ 4-CF3 S-Cl 4-Cl-Ph iPr CH2CH2C2Et 4-CF3 S-Cl CO2Et iPr C~2C~2C2Et .~ :
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4-Br H CO2Me tBu ~ ' ` 25 4-OCF3 H CO2Me tBu ~ .
; 4-CF3 S-Cl CO2Me tBu 4-C1 5-CI CO2Me tBu 4-8r S-CI CO2Me tBu 4-OCF3 5-Cl CO2Me tBu 4-CF3 5-Br CO2Me tBu 4-C1 5-8r CO2Me tBu 4-Br 5-Br CO2Me tBu 4-OCF3 S-~r CO2Me tBu -~ 4-CF3 4-F CO2Me tBu CO2Me tBu ' , , ' .
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~1 Rl R2 B Rlo 4-Br 4-F CO2Me tBu 4-OCF34-F CO2Me tBu 4-CF35-CF3 CO2Me tBu 4-CF35-F CO2Me ti3u 4-CF35-Cl Ph tBu 4-CF35-C14-Cl-Ph tBu 4-CF35-Cl c02Et tBu 4-CF3 H C~2Me Ph 4-Cl H CO2Me Ph 4-Br H CO2Me Ph 4-OCF3 H C02Me Ph 4-CF35-Cl CO2Me Ph 4-Cl S-Cl CO2Me Ph 4-Br S-Cl CO2Me Ph 4-OCF35-Cl CO2Me Ph 4-CF35-Br CO2Me Ph 4-Cl S-Br CO2Me Ph 4-Br S-Br CO2Me Ph 4-OCF35-Br CO2Me Ph 4-CF34-F CO2Me Ph 4-C14-F CO2Me Ph 4-F CO2Me Ph 4-OCF34-F C02Me Ph 4-CF35-CF3 C~2Me Ph n 4 CF35-F CO2Me Ph 4-CF35-Cl Ph Ph 4-CF35-C14-Cl-Ph Ph 4-CF3 S-Cl C02Et Ph ~:
4-CF3 H C02Me 4-Cl-Ph 4-CI H CO2Me 4-Cl-Ph 4-Br H CO2Me 4-Cl-Ph :
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2~3~?~30 Rl R2 Rlo . 4-OCF3 H CO2Me 4-Cl-Ph -CF3 5-Cl CO2Me 4-Cl-Ph 4-C1 5-Cl CO2Me 4 -Cl -Ph 4-8r 5-Cl CO2Me 4-Cl-Ph 4-OCF3 5-Cl CO2Me 4-Cl-Ph 4-CF3 5-8r CO2Me 4-Cl-Ph 4-C1 5-Br CO2Me 4-Cl-Ph .~
4-Br 5-8r CO2Me 4-Cl-Ph 4-OCF3 S-Br CO2Me 4-Cl-Ph 4 CF3 4 F C2Me 4-Cl-Ph 4-C1 4-F CO2Me 4-Cl-Ph .. 4-Br 4-F CO2Me 4-Cl-Ph 4-OCF3 4-F CO2Me 4-Cl-Ph Ç-CF3 5-CF3 CO2Me 4-Cl-Ph 4-CF3 5-F CO2Me 4-Cl-Ph ''~. - ,' .i, :~, .
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4-CF3 5-Br H O Me OEt 4-C1 5-Br H O Me OEt i 4-Br 5-Br H O Me OEt 4-OCF3 5-Br H O Me OEt ~, ~-CF3 5-Cl H O Me OEt .,. 4-C1 5-Cl H O Me OEt :~ 4-Br 5-Cl H O Me OEt ~= 4-CF3 S-C~3 H O Me OEt 4-CF3 4-F H O Me OEt 4-CF3 H H O Me OEt ; 4-CF3 S-Br CO2Me O Me OEt 4-CF3 5-Cl CO2Me O Me OEt 4 CF3 S-CF3 CO2Me O Me OEt ; 35 4 C~3 4-F CO2Me Me OEt .
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Z~f~0130 Rl R2 B V R~ ~9 . _ 4-CF3 H CO2Me Me OEt 4-CF35-Cl H S ~e OEt 4-C15-CI B S Me OEt 4-~r 5-CI H S Me OEt 4-CF35-Br H S Me OEt 4-CF35-F H S Me OEt 4-CF34-Cl H S Me OEt 4-CF34-F H S Me OEt 4-CF3 H N S ~e OEt , 15 4-CF35-Cl CO2Me S Me OEt - 4-CF35-Br CO2Me S Me OEt :` 4-CF35-F CO2Me S Me OEt 4-CF34-Cl CO2Me S Me OEt 4-CF34-F CO2Me S Me OEt 4-CF3 H CO2Me S Me OEt 4-CF35-Br B , O Me O-D-Bu 4-C15-Br H O Me O-n-Bu 4-Br 5-Br H O Me O-n-Bu ~; 4-OCF35-Br H O Me O-D-Bu . 25 4-CF35-Cl H O Me O-n-Bu 4-C15-Cl H O Me O-~-Bu i,~ 4-Br 5-Cl H O Me O-D-Bu -, 4-CF35-CF3 H o Me O-~-Bu . 4-CF34-F N O Me O-n-Bu 4-CF3 H B O Me O-n-Bu 4-CF35-Br CO2Ne o Me O-D-Bu .. 4-CF35-Cl CO2Me O Me O-n-Bu : 4-CF35-CF3 CO2Me O Me O-n-Bu 4-CF34-F CO2Me Me O-D-BU
' 35 4-Cr3 ~ CO2Me Me O-D-Bu h, 4-CF35-Cl H S Me O-D-Bu 4-C15-Cl N S Me O-n-Bu ." ~.'.
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-~ 4-CF34-F H O Me O-n-hexyl 4-CF3 H H O Me O-n-hexyl . 4-CF35-Br CO2Me O Me O-n-hexyl ; 4-CF3 s-Cl CO2Me O ~e O-n-hexyl 4-CF35-CF3 CO2Me O Me O-n-hexyl 4-CF34-F CO2Me Me O-D-hexyl 4-CF3 H CO2Me O Me O-n-he~yl 4-CF35-Cl H S Me O-n-hexyl 4-C15-Cl H S Me O-n-hexyl 4-Hr 5-Cl H S Me O-D-hexyl 4-CF35-Br H S Me O-D-hexyl 4-CF35-F H S Me O-n-he~yl . :
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Z~ ?~1;30 e6 4-CF34-Cl H S Me O-n-he~yl 4-CF34-F H S Me O-n-he~yl 4-CF3 ~ ~ S Me O-n-he~yl 4-CF35-Cl CO2~e S ~e O-D_~Y1 4-CF35-Br CO2Me S Me O-n-he~yl - 4-CF35-F ~02Me S Me O-n-hexyl 4-CF34-Cl CO2Me S Me O~-he~yl 4-CF3 ~-~ CO2Me S Me O-n-he~yl ; 4-CF3 H CO2Me S Me O-n-he~yl 15 4-CF35-Br H O Me O-n-octyl ' 4-C15-Br H O Me O-n-octyl 4-~r 5-Br H O Me O-n-octyl 4-OCF35-Br H O Me O-n-octyl 4-CF35-Cl H O Me O-n-octyl 4-C15-Cl H O Me O-n-octyl 4-Br S-Cl H O Me O-n-octyl ~: 4-CF35-CF3 ~ O Me O-n-octyl . 4-CF34-F H O Me O-n-octyl 4-CF3 H H O Me O-n-octyl 4-CF35-~r CO2Me O Me O-n-octyl 4-CF35-Cl CO2Me O Me O-n-octyl 4-CF35-CF3 CO2Me O Me O-n-octyl 4-CF34-F CO2Me Me O-n-octyl 4-CF3 H CO2Me Me O-n-octyl 4-CF35-Cl H S Me O-D-o~tyl 4-C15-Cl N ~ Me O-n-o.ctyl 4-~r 5-Cl H S Me O-n-octyl 9-CF35-Br H S Me O-n-octyl : ~-CF35-F H S Me D-D-octyl 4-CF34-Cl N S Me O-n-octyl 4-CF3 ~-F H S Me O-n-octyl 4-CF3 H HS Me O-n-octyl . , ' ~
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2t~01.~0 ~7 Rl R2 ~ V RB R9 _ 4-CF35-Cl CO2Me ~ Me O-D_OCtY1 4-CF35-~r CO2Me S Me O-D_~CtY1 4-CF35-F C2~e 5 Me O-n-octyl : 4-CF34-Cl CO2Me S Me O-D_OCeY1 4-CF34-F CO2Me S Me O-n-~ctyl 4-CF3 H CO2Me S Me O-n-octyl 4-CF35-Br H O He O-n-decyl . 4-C~ 5-Br H O Me O-n-decyl 4-Br 5-~r B O Me O-n-decyl 4-OCF35-Br H O Me O-n-decyl 4-CF35-Cl H O Me O-D-deCyl 9-C15-Cl H O Me O-n-decyl 4-Br S-Cl H O Me O-n-decyl ~ 4-C~35-CF3 H O Me O-n-decyl .~ 20 4-CF34-F H O Me O-n-decyl - 4-CF3 N H O Me O-n-decyl 4-CF35-ar CO2Me O Me O-n-decyl : 4-CF35-Cl CO2Me O Me O-n-decyl ~` 4-CF35-CF3 Co2Me o Me O-n-decyl :- 25 4-CF34-F CO2Me O Me O-n-decyl 4-CF3 H CO2Me Me O-n-decyl . 4-CF35-Cl H S Me O-n-decyl - 4-Cl S-Cl H S Me O-n-decyl 4-Fr 5-Cl H S Me O-n-decyl 3 S Me O-~-dccyl 4-CF35-F H S Me O-D-decyl ~-~ 4-CF34-Cl H S Me O-D-decyl 4-CF34-F H S Me O-n-decyl 4-CF3 H H ~ Me O-D-deCyl 4-C~35-cl CO2Me S Me O-D-decyl . 4-CF35-Br CO2Me S Me O-n-decyl 4-CF35-F CO2Me S Me O-~-decyl 4-CF34-Cl CO2Me S Me O-n-decyl ., :
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Rl R2 B V R8 R9 ~ 5 _ _ : 4-CF34-F CO2Me S Me O-n-decyl '! 4-CF3 H CO2Me ~ Me O-D-decyl 4-CF35-Rr H O Me O-n-dodecyl --~ 4-C15-~r ~ O Me O-n-dodecyl 4-~r 5-Br H O Me O-n-dodecyl : 4-OCF35-Br ~ O Me O-n-dodecyl 4-CF35-Cl H O Me O-n-dodecyl 4-C15-Cl H O Me O-n-dodecyl 4-Br 5-Cl H O Me O-D-dodecyl ~ 15 4-CF35-CF3 H O Me O-n-dodecyl : 4-CF34-F H O Me O-D-dodecyl 4-CF3 ~ H O Me O-D-dodecyl 4-CF35-Br CO2Me O Me O-n-dodecyl 4-CF35-Cl CO2Me O Me O-n-dodecyl 3 20 4-CF35-CF3 CO2Me O Me O-n-dodecyl ;~ 4-CF34-F CO2Me Me O-n-dodecyl 4-CF3 ~ CO2Me O Me O-n-aodecyl ; 4-CF35-Cl H S Me O-n-dodecyl , 4-C15-Cl H S Me O-n-dodecyl 4-~r 5-C18 S Me O-n-dodecyl ~; 4-CF35-~r H S Me O-n-dodecyl 4-CF35-F H S Me O-n-dod~cyl 4-CF34-Cl H S Me O-~-dodecyl 4-CF34-F H 5 Me O-n-dodecyl 4-CF3 H ~ S Me O-n-dodecyl 4-CF35-Cl CO2Me S Me O-n-dodecyl 9-CF35-B~ CO2Me S Me b-D-dodecyl 4-CF35-F CO2Me S Me O-D-dodecyl ` 4-CF34-Cl CO2Me S Me O-n-dodecyl 4-CF34-F C02Me S Me O-n-dodecyl :.
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2~0(:~130 ~9 Rl R2 ~ V R8 R9 5 .
4-CF3 H C02~e ~ Me O-D-d~decyl 4-CF3 5-8r H O Me O-sec-Bu 4-Cl S-ar H O Me O-cec-Bu 4-Br 5-Br H O Me O-sec-Bu 4-OCF3 5-Br ~ O Me O-rec-9u 4-CF3 5-Cl H O Me O-cec-Bu 4-C1 5-Cl H O Me O-cec-8u 4-Br ~-Cl H O Me O-cec-Bu 4-CF3 5-CF3 H o Me O-~ec-Bu 4 CF3 4 F H o Me 0-6ec-Bu -~- 4-CF3 H H O Me O-cec-Bu 4-CF3 5-Br C02Me O Me O-cec-Bu 4-CF3 5-Cl C02Me O Me O-~ec-Bu 4-CF3 5-CF3 C02Me O Me O-cec-Bu 4-CF3 4-F C02Me O Me O-cec-Bu 4-CF3 H C02Me O Me O-rec-Bu .:
4-CF3 5-Cl H S Me O-cec-Bu q-Cl 5-Cl H S Me O-cec-Bu . 4-Br 5-Cl H S Me O-~ec-Bu .. . .
4-CF3 S-Br H S Me O-cec-Bu '. 4-CF3 5-F H S Me O-cec-Bu 4-CF3 4-Cl N S Me O-~ec-Bu 4-CF3 4-F H S Me O-cec-Ku 4-CF3 H H S Me O-cec-8u 4-CF3 5-Cl C02Me S Me O-cec-Bu 4-CF3 5-Br C02Me S ~e O-sec-Bu 4-CF3 s-r C02Me S Me O-sec-Bu 4-CF3 d-Cl C02Me S Me O-cec-9u 4-CF3 4-F C02Me S Me O-cec-Bu ~-CF3 N C2M~ 5 lle O-~-c-Bu ;~''"
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; 20 4-CF3 4-F CO2Me S tBu S OEt OEt 4-CF3 H CO2Me S tBu S OEt OEt 4-CF3 5-Br H O tBu S -OCH2C(Me)2CH20-4-C1 5-Br H O t8u S -OCH2C(Me)2CH20-4-8r 5-Br H O tBu S -OCH2C(Me)2CH20-~. 25 4-OCF3 5-Br H O tBu S -OCH2C(Me)2CH20- ~.
`~X 4-CF3 5-Cl H O teu S -OCH2C(~e)2CH20-4-C1 5-Cl H O tBu S -OCH2C(Me)2CH20-4-Br 5-Cl H O t8u S -OCH2C(Me)2CHzO-4-CF3 5-CF3 H tBu S -OCH2C(M~)2CH20-4-CF3 4-F H O tBu S -OCH2C(Me)2CH2 . 4-CF3 H H O tBu S -OCH2C~Me)2C~20- -~
4-CF3 5-Br CO2Me O tBu S -OCH2G(Me)2CH20_ 4-CF3 5-Cl CO2Me O tBu S -OCH2C(Me~2CH20_ ; 4-CF3 5-CF3 CO2Me O tBu S -OCH2C(Me)2CH20-~`:' 35 4-CF3 4-F CO2Me O tBu S -OCH2C(Me)2CH20-4-CF3 H CO2Me t8u S -OCH2C(Me)2CH20-4 CF3 5-Cl H S t8u S ,OCH2c(Me)2Q20-"
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4-C1 5-Cl H S tBu ~ -OCH2C(Me)2CH2O-4-9r 5-Cl H S tBu S -OCH2C(Me)2CH2O-4-CF3 5-Br N S tBu S -OCH2C(Me)2CH20-4-CF3 5-F H S tBu S -OCH2C(Me)2CH2O-:: 10 4-CF3 4-Cl H S tBu S -OCH2C(Me)2CH2O-4-CF3 4-F H S tBu S -OCH2C(Me)2C~2 4-CF3 ~ H S t~u S -OCH2C(Me)2CH20-4-CF3 5-C~ CO ~ S t~u S -OCH2C(Me)2CH20-4-CF3 5-Bs CO2Me S tBu S -OCH2C(Me)2cH2 4-CF3 5-F CO2Me S tBu S OCH2C(Me)2c~2O-4-CF3 4-Cl CO2Me S tBu S -OCH2C(Me)2CH2O- ::
4-CF3 4-F CO2Me S tBu S -OCH2C(Ne)zCH2O-4-CF3 H CO2Me S tBu 6 -OCH2C(Me)2CH2O
~ 4-CF3 5-Br H O tBu S OCH2CH2CH2O-:. 4-C1 5-Br H O tBu S -OCN2CH2CH2O-4-Br S-Br H O tBu S -OCH2CH2CH2O-4-OCF3 5-2r H O tBu S OCH2CH2CH2O_ 4-CF3 5-Cl H O tBu S CH2cH2cH2-4-Cl S-CI H O tBu S -OCH2CH2CH2O-4-Br 5-Cl H O t~u S CH2CH2CH2O-4-CF3 5-CF3 H O tBu S -OCH2CH2CH2O-4-C~3 4-F H O tBu S -OCH2CH2CH2O_ 4-CF3 H H O tBu S -CH2cH2c~2-4-CF3 5-Br CO2Me O tBu S -OCH2CH2CH2O-`~ 30 4-CF3 5-Cl CO2Me O tBu S -OCB2CH2CH2O-4-CF3 5-CF3 CO2Me O tBu S -OCH2CH2CH2O-: 4-CF3 4-F CO2Me t~u S -CH2cH2~H2-~; ~-CF3 H CO2Me O tBu S -OCH2CH2CH2O-4-CB3 S-Cl H S tBu S -CH2cH2~H2-4-Cl S-Cl H S tBu S -OCH2CH2CH2O-4-Br S-Cl H S tBu S -OCH2CH2CH2O_ , .:. :
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2;11 C~C~130 . Rz fi V R8 Y' Y R~o 4-CF3 S-Br H S tBu S -ocH2cN2cH2o-4-CF3 5-F H S t8u ~ OCH2CH2CH20- .:
; 4-CF3 4-Cl ~ S tBu S -OCH2CH2CH20-; 4-CF3 4-F H S t~u S -OCH2C82CH20-4-CF3 N H S tBu S -CH2cH2cH2-4-CF3 5-Cl CO2Me S tBu S -~CH2CH2CH20- .
4-CF3 5-Br CO2Me S tBu S -OCH2CH2CH20- :
. 4-CF3 S-F CO2Me S tBu S -OCH2CH2CH20-4-CF3 9-Cl CO2Me S tBu S -OCH2CH2CH20-4-CF3 4-F CO2Me S tBu S -OCH2CH2CH20-. 4-CF3 H CO2Me S tBu S -OCH2CH2CH20-4-CF3 5-Br H O tBu S -OCH2CH20-. 4-Cl S-Br H O tBu S -OCH2CH20-``~ 4-Br S-Br H O tBu S -OCH2CH20- :
4-OCF3 5-Br H O t~u S -OCH2CH20- : .
; 4-CF3 S-Cl H O tBu S -OCH2CH20-4-C1 5-Cl N O tBu S OCH2CH20-4-Br 5-Cl H O tl3u S -OCH2CH20- ~,:
4-CF3 S-CF3 H O t8u S OCH2CH20-: 25 4-CF3 4-F H O tBu S -OCH2CH20-~ 4-CF3 H H O tBu S -CH2cH2-.,' 4-CF3 S-Br CO2Ne O tBu S -OCH2cH2 4-CF3 S-Cl CO2Me O tBu S OCH2CH20-4-CF3 S-CF3 CO2Me O tBu S -OCH2CH20-- 30 4-CF3 4-F CO2Me tBu S -OCH2CH20-s~ 4-CF3 H C02Me tBu S -OCH2CH20-4-CF3 5-Cl H S t8u S -OCH2CH20-``` 4-Cl S-Cl H S tBu S -OCH2CH20-4-Br 5-Cl H S tBu S -OCH2CH20-~, 35 4-CF3 S-Br H S tBu S -OCH2CH20- :~
4-CF3 S-F H S tBu S -OCH2CH20- :
4-CF3 4-Cl H S t~u S -OCH2CH20-., .
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: 1 22 ~ V RB Y y Rlo Y Rll 4-CF3 4-F H ~ tBu ~ -OCH2CH20-4-CF3 H N S tBu S -OCH2CH20-4-CF3 5-Cl CO2Me S tBu 5 -OCH~CH20-4-CF3 5-Pr CO2Me S tBu 5 -OCH2CH20-4-C~3 5-F CO2Me S tBu ~ -OCH2CH20-4-CF3 4-CI CO2Me S tBu S -OCH2CH20-4-CF3 4-F CO2Me S tBu S -OCH2CH20-4-CF3 H CO2Me S tBu ~ -OCH2C~20-4-CF3 5-~r ~ O lPr S OEt OEt 4-Cl S-Pr H O iPr S OEt OEt 4-Fr 5-Er H O lPr S OEt OEt 4-OCF3 5-Er H O iPr S OEt OEt 4-CF3 5-Cl H O iPr S OEt OEt 4-C1 5-Cl H O iPr S OEt OEt 4-Er S-Cl B O iPr S OEt OEt 4-CF3 5-CF3 H iPr S OEt OEt 4-CF3 4-F H O iPr S OEt OEt ; 4-CF3 H H O iPr S OEt OEt ::
4-CF3 5-Er CO2Mr O iPr S OEt OEt 4-CF3 S-Cl CO2Me O iPr S OEt OEt . 4-CF3 5-CF3 CO2Me O iPr S OEt OEt 4-CF3 4-F CO2He iPr S OEt OEt 4-CF3 H CO2Me O iPr S OEt OEt 4-CF3 5-Cl H, S iPr S OEt OEt 4-C1 5-Cl H S ~Pr S OEt OEt 4-Br 5-Cl H S ~Pr S OEt OEt 4-CF3 5-~r H S iPr S OEt OEt 4-CF3 5-E H S iPr S 3Et OEt -. 4-CF3 4-Cl H S iPr S OEt OEt 4-CF3 4-F N S iPr S OEt OEt 4-CF3 H H S iPr S OEt OEt . 4-CF3 5-Cl CO2Me S iPr S OEt OEt '. ;' ::
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- 4-CF3 5-~r CO2Me S iPr S OEt OEt 4 CF3 5-~ CO2Me S ~Pr S OEt OEt 4-CF3 4-Cl CO2Me S iPr S OEt OEt ~ 4-CF3 4-F CO2Me S iPr S OEt OEt .:` 10 4-CF3 H CO2Me S iPr 5 OEt OEt 4-CF3 S-Br H O iPr S -OCH2C(Me)2CN2O-. 4-C1 5-Br H O iPr S -OCH2C(Me)2CH20-~ 4-Br 5-Br H O iPr S -OCH2C~Me)2CH2O-4-OCF3 5-~r H O iPr S -OCH2C(Me)2CH2O-: 15 4-CF3 5-Cl H O iPr S -OCH2C(Me)2CH2O-~: 4-C1 5-Cl H O iPr S -OCH2C(Me)2CH2O-4-Br 5-Cl H O iPr S -OCH2C(Me)2CH2O-4-CF3 5-CF3 H iPr S -OCH2C(Me)~CH2O-4-CF3 4-F H O iPr S -OCH2C(Me)2CH2O-4-CF3 H H O iPr S -OCH2C(Me)2CH2O-4-CF3 5-Br CO2Me O iPr S -OCH2C(Me)2CH2O_ 4-CF3 S-Cl CO2Me O iPr S -OCH2C(Me)2CH2O-4-CF3 5-CF3 CO2Ne O iPr S -OCH2C(Me)2CHzO-4-CF3 4-F CO2Me O iPr S -OCH2C(Me)2CH2O-4-CF3 H CO2Me iPr S -OCH2C(Me)2CH2O-4-CF3 5-C~ H S iPr S -OCH2C(Me)2CH2O-~' 4-C1 5-Cl ~ . S iPr S -OCH2C(Me)2CB2O-4-Br 5-Cl H S iPr S -OCH2C(Me)2CH2O-4-CF3 5-Br H S iPr S -OCH2C(Me)2CH2O-4-CF3 5-F H S iPr S -OCH2C~Me)2CN2O-4-CF3 4-Cl H S iPr S -OCH2C(Me)2CH2O-~ 4-CF3 4-F B S iPr S -OCH2C(Me)2CH2O-4-CF3 H H S iPr S -OCH2C(Me)2CH2O-~-CF3 5-Cl CO2Me S iPr S -OCH2C(Me)2CH2O-4-CF3 5-Br CO2Me S iPr S -OCH2C(Me)2CH2O-~_~r3 5-~ C02Ye S Irr s -C~N2~r~)2~N2-. -.............................................................. . .
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4-CF3 ~-Cl C02Me S iPr S -OCHiC(Me)2CH20-4 CF3 4 F CO2Me S lPr S -OCH2C(Me)2CN20-4-CF3 8 CO2Me S iPr E -OCH2C(Me)2CH20-4-CF3 5-Br ~ O Me ~ OEt OEt 10 4-C1 5-Br H O Me S OEt OEt 4-Br S-Br H O Me S OEt OEt 4-OCF3 5-Br H O Me S OEt OEt 4-CF3 5-Cl H O Me S OEt OEt 4-C1 5-Cl ~ O Me S OEt OEt 15 4-Fr 5-Cl H O Me S OEt OEt 4-CF3 5-CF3 H O Me S OEt OEt 4-CF3 4-F H O Me S OEt OEt ~:~ 4-CF3 H H O Me S OEt OEt 4-CF3 S-Br CO2Me O Me S OEt OEt 4-CF3 S-Cl CO2Me O Me S OEt OEt 4-CF3 5-CF3 C02Me O Me S OEt OEt 4-CF3 4-F CO2Me Me S OEt OEt 4-CF3 H CO2Me Me S OEt OEt ~- 4-CF3 S-Cl H S Me S OEt OEt .` 25 4-Cl S-Cl H S Me S OEt OEt 4-Br S-Cl N S Me S OEt O~t 4-CF3 S-Br N S Me S OEt OEt ~.
4-CF3 S-F H S Me S OEt OEt ~; 4-CF3 4-Cl H S Me S OEt OEt 30 4-CF~ 4-F H S Me S OEt OEt 4-CF3 H H S Me S OEt OEt ::
i 4-CF3 S-Cl CO2Me S Me S OEt OEt . 4-CF3 S-~r CO2Me S Me S OEt OEt ; 4-CF3 5-F C02Me S Me S OEt OEt .. - 35 4-CF~ 4-Cl C02Me S Me S OEt OEt : 4-CF3 4-F CO2Me S Me S OEt OEt -~ 4-CF3 H CO2Me S Me S OEt OEt - .-' :. , ' ' . '.. : ,,: ,:,: .. .. ::. .: . .: . . :.: , . ::
-2~ 30 Rl R2 B V R~ Y Y Rlo Y Rll 4-CF35-Br H O tBu O OEt OEt 4-C15-Br H O t9u O OEt OEt 4-Br 5-Br H O tBu O OEt OEt 4-OCF35-9r H O tBu O OEt OEt 4-CF35-Cl H O t9u O OEt OEt 4-C15-Cl H O tBu O OEt OEt :~
4-Br 5-Cl ~ O tBu O OEt OEt - 4-CF35-CF3 B O tBu O OEt aEt 4-CF34-F H O tnu O OEt OEt 4-CF3 H H O t8u O OEt OEt ,. 4-CF35-Br COzMe O t8u O OEt OEt 4-CF35-Cl CO2Me O tBu O OEt OEt 4-CF35-CF3 CO2Me O t9u O OEt OEt - 4-CF34-F CO2Me t8u O OEt OEt 4-CF3 H CO2Me t8u O OEt OEt 4-CF35-CI H , S t8u O OEt OEt ,.'. 4-C15-Cl H S tBu O OEt OEt :.Y- 4-9r 5-Cl H S t8u O OEt OEt . 4-CF35-8r H S tBu O OEt OEt 4-CF35-F H S tBu O OEt OEt 4-CF34-Cl H S tBu O OEt OEt 4-CF3 q-F H S tBu O OEt OEt ;~ 9-CF3 H ~ S tBu O OEt OEt `~' 4-CF35-Cl CO2Me S tBu O OEt OEt , 30 4-CF35-Bs CO2Me S tBu O OEt OEt 3 4-CF35-F CO2Me S tBu O OEt OEt ~ 4-CF34-Cl CO2Me S t8u O O~t OE~ :-.. 4-CF34-F CO2Me S tBu O OEt OEt : 4-CF3 H CO2Me S tBu O OEt OEt :' .`' . ' , .
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4-CF35-~r ~ O t8u O -OCH2C~Me)2CH2O-: 4-C15-Br H O tBu O -OCH2C(Me)2CN2O-4-8r 5-Br H O t8u O _ocH2c(Me)2~H2o 4-OCF35-Br H O tBu O -OCH2C(Me)2CN2O
104-CF35-Cl H O t8u O -OCH2ClMe)2CH2O-4-C15-Cl H O tHu O -OC~2C(Me)2CH2O-4-Br 5-Cl H O tBu O -OCH2C(Me)2CH2O-4 CF35-CF3 H ~ t8u O -OCH2C(Me)2CH2O-4-CF34-F H O tBu O -OCH2C(Me)2CB2O-154-CF3 ~ H O t8u O -OCH2C(Me)2CH2O-4-CF3 5-Br CO2Me O tBu O -OCH2C(Me)2C~2O-4-CF3 5-Cl CO2Me O tBu O -OCH2C(Me)2CH2O-4-CF3 5-CF3 CO2Me O tBu O -OCH2C(Me)2CH2O-4-C}3 4-F CO2Me O t8u o -OCH2C(Me)2CH2O-4-CF3 N CO2Me t8u O -OCH2C(Me)2CH2O-4-CF35-Cl H S tBu O -OCH2C(Me12CH2O-4-C15-Cl N S tBu O -OCH2C(Me)2CH2O-- 4-8r 5-Cl H S t8u O -OCH2C(Me)2CH2O-4-CF35-Br H S t8u O -OCH2C(Me)2CH20-254 CF35-F H S t8u o -OCH2C(Me)2CN2O--CF34-Cl H S t5u O -OCH2C(Me)2CH2O-. 4-CF34-F H S t8u O -OCH2C(Me)2CH2O- :~
4-CF3 H N S tBu O -OCH2C(Me)2CH2O-4-CF35-C~ C~2Me S tBu O -OCH2C(Me)2CH20-4-CF35-Fr CO2Me S tBu O -ocHzc(Me) 4-CF35-F CO2Me S tBu o -OCH2C(Me)2CH2O-4-CF34-C~ C02Me S t~u O -OCH2C(Me)2CH20-4-CF3 q-F C02Me S tBu O -OCH2C(Me)2CH20-4-CF3 N CO2Me S tBu O -OCH2C(Me)2CH2O-: 35 . "
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4-CF35-CF3 co2Me O iPr O Et OEt 4-CF34-F CO2Me lPr O St OEt 4-CF3 H CO2Me iPr O Et OEt ~ 4-CF35-Cl H S iPr O ~t OEt : 10 4-C15-Cl H S iPr O Ft OEt 4-Br 5-Cl H S lPr O Et OEt ; 4-CF35-Br H S iPr O Et OEt 4-CF35-F H S lPr O Et OEt . 4-CF34-Cl H S iPr O Et OEt :: 15 4-CF34-F H S iPr O Et OEt 4-CF3 H N S iPr O Et OEt 4-CF35-Cl co2Me S iPr O Et OEt . :
4-CF35-Br CO2Me S iPr O Et OEt 4-CF35-F CO2Me S iPr O Et OEt : 20 4-CF34-Cl CO2Me S iPr .O Et OEt 4-CF34-F CO2Me S iPr O Et OEt 4-CF3 H CO2Me S iPr O Et OEt 4-CF35-Br N O iPr O Et O-iPr ; .
4-C15-Br H O iPr O Et O-iPr , 25 4-Br 5-Br H O iPr O Et O-iPr 4-OCF35-Br H O iPr O Et O-iPr 4-CF35-Cl H O iPr O Et O-iPr '.~ 4-Cl S-Cl H O iPr O Et O-iPr 4-8r 5-Cl N O iPr O Et O-iPr 4-CF35-CF3 H O ~Pr O Et O-lPr 4-CF34-F H O iPr O Et O-iPr 4-CF3 H H O iPr O - Et O-iPr -:' 4-CF35-8r CO2Me iPr O Et O-~Pr ~-CF35-Cl CO2Me O lPr O Et O-lPr q-CF35-CF3 C2Me O ~Pr O Et O-iPr 4-CF34-F CO2Me O iPr O Et O-iPr ~ 4-CF3 H CO2Me iPr O Et O-iPr .~ .- .
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4-CF3 H ~02Me S iPr O Et OPh ;.~ 4-CF3 5-Br H 0 iPr O Ph OEt 4-C1 5-}lr H O iPr O Ph OEt : 2 o 4-E~r 5-EJr H O iPr O Ph OEt 4-OCF3 5-Br H O ~Pr O Ph OEt q-CF3 5-Cl H O iPr OPh OEt .~ 4-C1 5-Cl H O iPr OPh OEt .
4-Br 5-Cl H O iPr OPh OEt . 2 5 4-CF3 5-CF3 H o iPr OPh OEt 4-CF3 4-F H O iPr OPh OEt .~ 4-CF3 H H O iPr O Ph OEt 4 CF3 S-E~r C02Me O lPr O P2~ OEt 4-CF3 5-Cl CO2Me .O ~Pr O Ph OEt ~l-cF3 5_~ F3 C02Me O iPr O Ph OEt ~-CF3 ~-F C02Me lPr O Ph OE;t -~, 4-CF3 H CO2Me O iPr O Ph OEt 4-CF3 5-C~ a ~ iPr O Ph OEt 4-Cl S-Cl ~1 5 iPr O Ph O~:t : --.
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Z~00130 R2 B V 28 Y' RlC Y Rll 4-CF3 H H S tBu O Et, . OEt 4-CF3 5-Cl C02Me S tBu O Et OEt ~l-cF3 S-Br CO2Me S tBu O Çt OEt 4-CF3 5-F C02Me S tBu O Et OEt ~.
4-CF3 4-Cl CO2Me S tBu O Et OEt 4-CF3 4-F CO2Me S tBu O Et OEt 4-CF3 13 C02Me S tBu O Et OEt 4-C1 5-Br H O iPr S Et O-~Pr 4-Br 5-Br H O iPr S Et OPh 4-OC~3 5-Br H C> iPr S Ph OEt 4-CF3 5-Cl H O iPr S Ph O-iPr .~ 4-C1 5-Cl H O iPr S Ph OPh 4-Br S-Cl ~ O tBu S Et OEt '-' 4-CF3 5-CF3 H tBu S Et O-iPr 2 0 4-CF3 4-F H O tBu S Et OPh ; 4-CF3 H H O tBu S Ph OEt 4-CF3 5-i3r CO2Me tBu S Ph O-iPr ~,; 4-CF3 5-Cl CO2Me O tBu S Ph OPb -.~ 4-CF3 5-Br H S iPr S ~Pr OEt . 2 5 4-CF3 5-F H S iPr S iPr O-iPr ~- 4-CF3 4-Cl H S iPr S iPr OPh 4-CF3 4-F H S iPr S DPr OEt 4-CF3 H H S iPr S nPr O-iPr 4-CF3 5-Cl C2Me S iPr S nPr OPh ~ i 3 o 4-CF3 5-Br C02Me ~; tBu S Me OEt i~ ;
4-CF3 5-F C02~e S tBu S ~Se O-iPr ~ "
- e-CF3 4-Cl C02Me S tBu S Me OPh ~~
4-CF3 ~-F C02Me S ~Bu E; ~lle O-sec-8u '`
4-CF3 H CO2Me S tBu S Me O-nPr .
,, .
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, ,,, ' . ", 2~C~0130 T~ble 12 : 5 lC
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:: 15 OR
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:. Rl a2 .B V Rlo Rll :. . ~ .
'. 4-CF3 5-8r H O Et Et 4-C1 5-Br H O Et Et 4-8r 5-Br H O Et Et . 4-OCF3 5-8r H O Et Et 4-CF3 S-Cl ~ Et Et 4-C1 5-Cl N O Et Et ; 4-Br 5-Cl H O Et Et 4-CF3 5-C~3 H o St Et 4-CF3 4-E H O Et Et 4-CF3 H H O Et Et ` 4-CF3 5-Br CO2Me O Et tt :' 4-CF3 5-CI CO2Me O ~t Et . . .
~ ~ .
; - ' , 2~00130 Rl R2 E~ V Rlo R
: 5 4-CF3 5-CF3 C~2Me O Et St ~-CF3 q-F C2M~ Et Et 4-CF3 H C2~e ~t Et - 4 CF3 S-Cl ~ S Et Et 4-C1 5-Ci H S Et Et 4-Br 5-Cl H S Et Et 4-CF3 5-9r H S Et Et 4-CF3 5-F H S Et Et 4-CF3 4-Cl H S Et St 15 4-CF3 4-F H S Et Et :-; 4-CF3 H H 5 Et Et '; 4-CF3 5-Cl C02Me S St Et 4-CF3 5-9r C02Me S Et Et 4-CF3 5-F C02Me S Et Et ., 20 4-CF3 4-Cl C02Me S Et. Et `~: 4-CF3 4-F C02Me S Et Et 4-CF3 H C02Me S Et St , ~5 .
, . .
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. . , ... . .
,, 35 .
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~. . , . . . . .. 1 . . . .. . - : . ..... . : ... .. . , .. -2;~ 0~3~U
~ble 13 :
N-N ~ 1 .~ ~N `, ' 15 S-N-Re , R, 2 .
,: .
:~ 20 :~.; Rl R2 B V RB R12 . .. i .
.~ 4-CF3 5-Br H O nBu DBu .; 4-C1 5-Br H O n9u DBu .. 25 4-Br 5-Br H O nBu ~Bu :. 4-OCF3 5-8r H O nBu nBu 4-CF3 5-Cl H O n8u DBu ~.~ 4-C1 5-Cl H O ~Bu nBu :.' 4-Br 5-Cl H O nBu nBu . 30 4-CF3 5-CF3 H O nBu ~Bu ,ri 4-CF3 4-F H O nBu D8U
.X 4-CF3 H ~ DBu DBu 4-CF3 5-8r CO2Me D8U n8u 4-CF3 5-Cl CO2Me O DBu nBu 4-CF3 5-CF3 CO2Me o D8U DBU
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2~C~0~310 .:.
. Rl R2 B V R,3 ~12 4-CF3 4-F C02Me nBu ~113U
. 4-CF3 B C02Me ~Bu n~3u 4-CF3 5-Cl H ~ nBu l~Bu 4-C1 5-Cl H S nl~u DBu ~-8r 5-Cl H S l~Bu ~Bu 4-CF3 5-Br H S nBu nBu 4-CF3 5-F ~ S nBu nBu 4-CF3 4-Cl ~1 5 ~Bu nl~ ~
4-CF3 4-F H S nBu nBu ~ ~ `
4-CF3 H H S nBu nBu ` 4-CF3 5-Cl CO2Me S nBu nBu . !
4-CF3 5-Br CO2Me S nBu nBu -~:
.~ 4-CF3 5-F CO2Me S rlBu ~Bu 4 CF3 4-Cl C02~e S nBu IlBu 2 0 4-CF3 4-F C02Me S nl~u nBu 4-CF3 H CO2Me 5 ~IBu nBu 4-CF3 5-Br H O -cH2c82cHzcH2cH2 4-C1 5-Br H O -CH2CH2CH2cH2cH2-4-Br 5-Br H O -CH2CH2CH2cH2cH2-. 2 5 4-OCF3 S-Br 8 O -CH2CH2CH2cH2cH2 4-CF3 5-Cl ~ O -CH2CH2CH2cH2cH2 .~. 4-C1 5-CI H O -cH2cH2cH2cH2cH2 4-Br 5-Cl H O -C82CH2CH2CH2cH2 . 4-CF3 5-CF3 H o -CH2CH2CH2cH2cH2-3 o 4-CF3 i-F H O -CH2CH2CH2cH2cH2-. 4-CF3 H H O -CN2CH2CH2cH2cH2-:: 4-CF3 5-13r ~:02Me O _C~i2C~2CH2CH2cH2-4-CF3 5-Cl CO2Me O -CH2C~2CB2cH2cH2-4-CF3 5-CF3 CO2Me O -CH2C~2CH2cH2c~2-3 5 3 CO2Me O -CN2CH2C~2cH2cH2-; 4-CF3 H CO2Me O -CH2CH2CH2cH2cH2-4-CF3 5-Cl H S -cH2cH2cH2cH2cH2 .,' .
,' ., .
.
21~0(~130 Rl R2 B Y R8 R12 _.
4-C1 5-Cl H S -CH2CN2CH2cH2cH2-4-Br S-Cl H 5 -CH2CH2CH2CH2cH2-4-CF35-Br H S -cH2c~2cH2cH2cH2-; 4-CF35-F H S -CH2CH2CH2cH2cH2-4-CF34-Cl H S -CH2CH2CH2cH2cH2 4 CF34-F H S -CH2CH2CH2cH2cH2 : q-CF3 H H S -CH2CH2CH2cH2cH2 4-CF35-Cl C02Me ~ -cHzcH2cH2cH2cH2 4-CF35-Br C2Me S -CH2CH2CH2CH2CH2_ 4 CF35 F C2M~ S -CH2CH2CH2CH2CH2_ 9-CF34-Cl C02Me S -CH2CH2CH2CH2CH2_ 4_CF34_F C02Me ~ -CH2CH2CH2cH2cH2-:; 4-CF3 H C02Me S -CH2CH2CH2cH2cH2-4-CF35-Br H O -CH2CH20CB2cH2-4-C15-Br H O -CH2cN20cH2cH2 4-Br 5-Br H O -CH2cH20cH2cH2 . 4-OCF35-Br H O -CH2CH20CH2CH2 4-CF35-~1 H O -CH2CH20CH2cH2 4-C15-Cl ~ O -CH2cH20cH2cH2 i 25 4-Br 5-Cl H O -CH2CH20CH2cH2 '` 4-CF35-CF3 H O -CH2cH20cH2cH2 . 4-CF34-F H O -CH2CH20CH2cH2-4-CF3 H H O -CH2CH20CH2cH2 4-CF35-Br C02Me -CH2CH20CH2CH2-. . 30 4-CF35-cl co2Me O -CH2CH20CH2c~2-4-CF35-CF3 C02Me o -CH2cH20~H2cH2 4-C~34-F C02Me -cH2cH2ocH2cN2 4-CF3 H C02Me O -CH2cH20cH2cH2 4-CF35-Cl N S -CH2C~20C~2cH2 4-Cl S-Cl H S -CH2cH20cH2c~2 4-Br 5-Cl H S -CN2CN20CH2CH~
4-CF35-i3r H S -CH2CH20CH2CH2_ Z1~ 30 Rl R2 B V Re R12 ~
4-CF34-C18 S -CH2CH20~H2CH2_ ~
4-CF34-F H S -CH2CH20CH2cH2 4-CF3 H B S -C~zCH20C~2C82-4-CF35-Cl CO2Me S -CH2CH20CH2cH2 . 10 4-CF35-Br CO2Me S -CH2CH20CH2CH2-: 4-CF35-F CO2Me S -CH2CH20CH2cH2-4-CF34-Cl CO2Me S -CH2CH20CH2CH2_ ~ .
4-C~34-F C02Me S -CH2cH20c~2cB2 4-CF3 H CO2Me S -CH2cH20cH2cH2-4-CF35-Br H O -CH2CNMeOCHMeCH2_ 4-C15-Br H O -CH2CHMeOCHMeCH2-4-Br 5-Br H O -CH2CHMeOCHMeCH2_ 4-OCF35-Br H O -CH2CHMeOCHMeCH2-`~ 4-CF35-Cl H O -CH2CHMeOCHMeCH2-;' 20 4-C15-Cl H O -CH2CHMeOCHMeCH2-4-Br 5-Cl H O -CH2CWeOCHMeCH2_ : -. 4-CF35-CF3 H O -CH2CHMeOCHMeCH2-,~ 4-CF34-F H O -CH2CHMeOCHMeCH2- .
. 4-CF3 H H O -CH2CHMeOCXMeCB2_ ,,.
4-CF35-Br CO2Me O -CH2CNMeOCHMeCH2-4-CF35-Cl CO2Me O -CH2CWeOCHMeCH2_ 4-CF35-CF3 CO2Me O -CH2CHMeOCHMeCH2-:
4-CF34-F CO2Me -CH2CHMeOCHMeCH2- :
4-CF3 H ,C02Me -CH2CHMeOCHMeCH2-30 4-CF35-Cl ~ S -CH2CWeOCHMeCH2-i 4-C15-Cl ~ S -CHzCHMeOCHMeCH2-: 4-~r 5-Cl H S -CB2CHMeOCHMeCH2-4-CF35-Br H S -CH2CHMeOCHMeCH2_ .~ 4-CF35-F H S -CH2CHMeOCHMeCH2 4-CF34-Cl H S -CH2CWeOCHMeCH2-4-C~34-F H 5 -CH2CHMeOCHMeCH2-'t ., ~
; ' ,:. , ., .
: ~ z~(~o~ o Rl ~2 ~ V R8 R12 ..
4-CF3 H H S -CH2C~MeOCHMeCH2-4-CF35-Cl C02Me S -CH2CHMeOCHMeCH2-4-CF35-Br ~02Me S -CH2CHMeOCHMeCH2-4 C~35-F C02Me ~ -CH2CHMeOCHMeCH2-4-CF3 ~-Cl CO2M~ S -CH2CHMeOCHMeCH2-4-CF34-F C02Me S -CH2CHMeOCHMeCH2-4-CF3 H C02Me S -CH2CHMeOCHMeCH2-4-CF35-Br H O ~t c 4-C15-Fr H O ~t cyclo-C6H
-- 15 4-Br 5-Rr H O Et cyclo-c6 ,.1 4-OCF35-Br H O Et cyclo-C6H
4-CF35-Cl H O Et 4-C15-Cl H O Et 4-Br 5-Cl H O Et cyclo-C6H
.~ 20 4-CF35-CF3 H o Et cyclo-c6H
4-C~34-F H O Et cyclo C6H
4-CF3 H N O Et cyclo-C
4-CF35-Br CO2Me Et Cyclo-c6H
~-CF35-Cl C02Me ~t Cyclo-c6Hll 4-CF35-CF3 co2Me O Et cyclo-C6H
. . 4-CF3 ~-F CO2Me Bt cyclo-C6H
4-CF3 ~ CO2Me Et cyclo-C6H
4-CF35-CI H S Et cYClo-C6H
4-C15-Cl H S Et ~YCl~~6Hll 4-Br 5-Cl H S Et cyclo-C6H
. 4-CF35-Br H S Et cyclo-C6H
4-CF35-F H S Et cyclo-C6H
4-CF34-Cl H S Et cyclo-C6H
~F34-E H S Et CYC1~
4-Cr3 H H 5 Et ~YCl-c6Nll 4-CF35-~1 c02Me S Et CYC1-C6Hll .', . ' .
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2C~Q01 3(~ ~
~28 Rl R2 El V R8 R12 4-CF3 5-Br C02Me S Et Cyelo-c6H
4-CF3 5-F CO2Me S Et ~yclo-C6H
4-CF3 4-Cl CO2Me S Et cyclo-c6 4-CF3 4-F CO2Me S Et c ~S-CF3 H C02Me S E;t CYC1-4-CF3 5-Elr B t) iPr CN2CH2C2Et :. 4-Cl S-Br H O iPr CH2CH2C2Et 4-Br 5-Br H O iPr t H2CH2C2Et 4-OCF3 5-Fr H O iPr CH2CH2CO2Et `: 15 4-CF3 5-Cl H O iPr CH2CH2CO2Et 4-C1 5-Cl H O iPr CHZCH2CO2Et 4-Br S-Cl H O iPr CH2CH2CO2Et 4-CF3 5-CF3 H O iPr CH2CH2C2Et 4-CF3 4-F H O iPr CHZ~H2CO2Et 2 0 4-CF3 H H O iPr CHZCH2CO2Et 4-CF3 5-Br CO2Me iPr CH2CH2CO2Et 4-CF3 5-Cl CO2Me O ~Pr CH2CH2CO2Et 4-CF3 5-CF3 CO2Me O iPr CH2CH2C2Et 4-CF3 4-F CO2Me iPr CH2CH2~2Et 2 5 4-CF3 H CO2Me iPr CH2CH2CO2Et 4-CF3 5-Cl H S iPr CHZCH2CO2Et 4-C1 5-Cl H S iPr CH2CH2C2Et ` 4-Br 5-Cl H S iPr CH2CH2C2Et 4-CF3 5-Br H S iPr CH2CH2C2Et 3 0 4-CF3 5-F H S iPr CH2CH2CO2Et 4-CF3 4-CI H S iPr CHZCH2EO2Et 4-CF3 4-F H S iPr CN2CH2CO2Et -,: 4-CF3 H H S iPr CH2CH2CO2Et 4-C~3 5-Cl CO2Me S iPr CH2CN2CO2Et 3 5 'I-CF~ 5-Br CO2Me S iPr CNZCH2CO2Et 4-CE3 5-F CO2Me S iPr CH2CHzCO2Et , ".
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Z~ 0130 12g .
Rl R2 B V R8 R12 4-CF3 4-Cl CO2Me S iPr CH2CH2C2Et . 4-CE3 4-F CO2Me S ~Pr CH2CH2CO2E~
4-CF3 H CO2Me S . ~Pr CH2CH2CO2Et :
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.. 20 Rl R2 ~ V Rlo :. 4-CF3 5-Br H O tBu .
-Cl 5-Br H O tBu 4-Br 5-Br H O tBu ::
254-OCF3 5-8r H O tBu 4-CF3 5-Cl H O tBu -~ 4-C1 5-Cl H O tBu ~ 4-Br 5-Cl H O tBu - 4-CF3 5-CF3 H O tBu 304-CF3 4-F H O tBu -j, 4-CF3 H H O t~u 4-~F3 5-Br CO2Me O tBu q-CF3 5-Cl CO2Me t~u 4-CF3 5-CF3 CO2Me O tBu , 35 ~-CF3 4-F CO2~e tBu . ~:
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2~(~Q130 Rl R2 ~ V Rlo 5 .
4-CF3 H C02Me tBu 4-CF3 5-Cl H S ~Bu 4-C1 5-Cl H S tElu 4-Br 5-Cl H S ti3u 4-CF3 5-Br H S tBu 4-CF3 5-F H S tBu 4-CF3 4-Cl H ~; tBu 4-CF3 4-E` ~i S tBu 4-CF3 H H S tElu 4-CF3 5-Cl C02Me S tBu 4-CF3 5-~r CO2Me S tBu 4 CF3 5-F CO2Me S tBu 4-CF3 ~-Cl CO2Me S tBu ~ 4-CF3 4-F CO2Me S tBu ,~ 20 4-CF3 N CO2Me S tBu - 4-Br 5-C1 H ' S cec-Bu 4-CF3 5-Br H S sec-Bu 4-CF3 5-F H 5 c~c-Bu - 4-CF3 4-Cl H S sec-Bu 2 5 4-CF3 4-F H S sec-Bu 4-CF3 H H S sec-Bu 4-CFj S-Cl CO2Me S sec-Bu .' q-CF3 5-Br CO2Me S sec-Bu 4-CF3 5-F C02Me S cec-Elu C 9 CF3 4-Cl CO2Me S ~c-Bu ` 4-CF3 4-F C02~e S e~c-llu , 4-CF3 H CO2Me 5 sec-Bu 4-CF3 5-Br N O Ph 4-C1 5-Br H O Ph 4-Br 5-llr H O Ph 4-OCF3 5-Br H O Ph .. . .
,. .
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~ 2~ tO~30 ' .
2 _ V Rlo 4-CP3 S-Cl H O Ph 4-C1 5-Cl H O Ph 4-Br 5-Cl H O Ph 4-CF3 5-CF3 H o Ph 4-CF3 4-F H O Ph 4-CF3 H H O Ph 4-CF3 S-~r CO2Me Ph ~.
4-CF3 5-Cl CO2Me Ph :~ 4-CF3 5-CF3 CO2Me o Ph 4 CF3 4-F CO2Me Ph 4-CF3 H CO2Me Ph 4-CF3 5-Cl H S Ph , 4-Cl S-Cl H S Ph 4-Br 5-Cl H S Ph :~ 2 0 4-CF3 5-Br N S Ph ;~ 4-CF3 5-F H S Ph 4-CF3 4-C1 0 S Ph , 4-CF3 4-F H S Ph . 4-CF3 H H S Ph :'. 2 5 4-CF3 5-Cl CO2Me S Ph ^ 4-CF3 5-Br CO2Me S Ph 4-CF3 5-F CO2Me S Ph .;~ 4-CF3 4-Cl CO2Me S Ph s~ 4 CF3 4 F Ç02Me S Ph 3 o 4-CF3 H CO2Me S Ph 4-CF3 5-Br S~ O ~-Cl-Ph .` 4-C1 5-Br H O 4-Cl-Ph 4-~r 5-Br H O 4-Cl-Ph 4-OCF3 5-~r H O 4-Cl-Ph 3 5 4-C~3 5-Cl H O 4-Cl-Ph 4-C1 5-C1 11 0 4-Cl-Ph .. . ..
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Rl R2 B V Rlo 4-8r 5-Cl H O 4-Cl-Ph 4-CF35-CF3 H o ~-Cl-Ph 4-CF34-F H O 4-Cl-Ph 4-CF3 ~ H O 4-Cl-Ph 4-CF35-Br CO2Me 4-Cl-Ph 4~CF35~cl CO2Me 4-Cl-Ph 4-CF35-CF3 CO2Me O 4-Cl-Ph 4-CF34-F CO2~e ~ 4-~1-Ph 4-CF3 H CO2Me O 4-Cl-Ph 4-CF35-Cl H S4-Cl-Ph 4-C15-Cl H S4-Cl-Ph 4-Br 5-Cl H S4-Cl-Ph 4-CF35-Br H S4-Cl-Ph 4-CF35-F H S4-Cl-Ph 4-CF34-Cl H S4-Cl-Ph 4-CF34-F ~ S4-Cl-Ph 4-CF3 H H S4-Cl-Ph .~ 4-CF35-Cl CO2Me S4-Cl-Ph . 4-CF35-Br CO2Me S4-Cl-Ph . 25 4-CF35-F CO2Me S4-Cl-Ph i~ 4-CF34-Cl CO2Me S4-Cl-Ph 4-CF34-F CO2Me S 4-Cl-Ph 4-CF3 H CO2Me S 4-Cl-Ph ?0 ": . ,:
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~a~ 130 . ~' .
~ble 15 . '' .
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~',!j 20 ~1 R2 Rl3a 13 ~ - R8 Rg E 4-CF3 5-F Me Me S Me OEt . 4-CF3 5-Cl Me Me S Me OEt 7 . 4-CF3 4-F Me Me S Me OEt ., 25 4 CF3 S-Br Ph H O Me OEt 4-CF3 5-Br CO2Me H o Me OEt 4-CF3 S-Br Me Me O Me OEt :~ 4-CF3 5-Cl Me Me O Me OEt 4-CF3 S-F Me Me S Me O-nBu ~ 30 4-CF3 S-Cl Me Me S Me O-nBu :~
". 4-CF3 4-F Me Me S Me O-nBu 4-CF3 S-Br Ph ~ O Me O-~Bu ~-CF3 5-Fr CO2Me H O Me O-nBu 4-CF3 S-~r Me Me O Me O-n9u ~-CF3 S-Cl Me Me O Me O-nBu .
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135 .:
Rl R2 R 3~ R b V R8 Rg , - . .
4-CF35-F Me Me S Me O-DHeryl 4-CF35-Cl Me Me ~ Me O-nHesyl 4-CF34-F Me Me S Me O-nBe~yl 4-CF35-Br Ph H O Me O-nHe~yl . 10 4-CF35-Br C02Me H O Me O-~He~yl 4-CF35-Br Me Me O Me O-nHe~yl 4-CF35-Cl Me Me O Me O-nHexyl 4-CF35-F Me Me 6 Me O-~ec-9u 4-CF35-Cl Me Me S Me O-sec-Bu 4-C}34-F Me Me S Me O-oec-Bu 4-CF35-Br Ph H O Me 0-6ec-Bu 4-CF35-Br C02Me H O Me O-see-Bu 4-CF35-Br Me Me O Me O-sec-Bu 4-CF35-Cl Me Me O Me O-~ec-Bu :~.
4-C~35-F Me Me S Me O-lPr 4-CF35-Cl Me, Me S Me O-lPr .:~
4-CF34-F Me Me S Me O-iPr . 4-CF35-Br Ph H O Me O-lPr 2 4-CF35-Br C02Me H O Me O-iPr -` 25 4-CF35-Br Me Me O Me O-iPr .
4-CF35-Cl Me Me O Me O-iPr 4-CF35-F Me Me S Me OCH2CH20Et 4-CF35-Cl Me Me S Me OCH2CH20Et 4-CF34-F Me Me S Me OCH2CH20Et 4-CF35-9r Ph H O Me OCH2CH20Et .j 4-CF35-Br C02Me H O Me OCH2CH20Et 4-CF35-Br Me Me O Me . OCH2CH20Et ,- 4-CF35-Cl Me Me O Me OCH2CN20Et : 4-CF35-F Me Me S Me F
3S 4-CF35-Cl Me He S Me F
:~ 4-CF34-F Me Me S Me ,'' . ~ ~,:
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2~ 30 R2 R13~ R b V R8 Rg 4-CF35-Br Ph H O Me . F
4-C~35-Br CO2Me H O t~5e F
4-CF35-l~r l~le ~e O Me F
. ~ 4-CF35-Cl ~e Me O Me F
4-C~35-F Me Me 6 Me NMe2 4-CF35-Cl Me Me S Me NMe2 : 4-CF34-F Me Me S Me NMe2 4-CF35-Br Ph H 0 ~le NMe2 4-CF35-~r CO2Me H O Me NMe2 4-CF3 5-Br Me Me 0 ~5e NMe2 4-CF3 5-Cl Me Me O Me NMe2 4-CF3 5-F Me Me S Et O-iPr 4-CF3 5-Cl Me Me S Et O-iPr 4-CF3 4-F Me Me S Et O-iPr 4 -CF35-Br Ph H O Et O-iPr 4-CF35-Br CO2Me H O Et O-iPr 4-CF35-Br Me Me O Ct O-iPr ~:
4-CF3 5-Cl Me Me O Et O-iPr 4-CF3 5-F Me Me S iPr OEt :
4 -CF3 5-Cl Me Me S iPr OEt .. 4-CF3 4-F Me Me S iPr OEt 4-CF3 5-Br Ph H O iPr OEt ~,~ 4-CF3 5-Br CO2Me H O iPr OEt 4-CF3 5-Elr Me Me O iPr OEt 4 -CF35-Cl Me Me O iPr ClEt 4-CF35-F Me Me S iPr OCH2CF3 4-CF35-Cl Me Me S iPr CIJ2CF3 :. q-CF34-F Me Me S iPr OCH2cF3 4-CF35-Br P~ H O ~Pr OCH2cF3 35 4-CF35-Br C02Me H O iPr C~CH2~r3 4-CF35-Br Me Me O iPr OCH2CF3 ., .
, .. . .. ..
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R2 R13 Rl3b V R8 Rg 4-CF3 5-Cl Me Me O lPr OCH2CF3 4-CF3 5-F Me Me ~ 1Pr OCH2C02Me ~ 4-CF3 S-Cl Me Me S lPr OCH2C2Me : 4-CF3 4-F Me Me S ~Pr OCH2C02Me 4-CF3 5-Br Ph H O ~Pr OCH2C02Me 4-CF3 5-Br C02Me H O ~Pr OCH2CO~Me : 4-CF3 S-Pr ~e Me O iPr OCH2C02Me 4-CF3 5-Cl Me Me O lPr OCH2C02Me ` 15 . .
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Table 16 ,,' S
; 10 Ra~3 :-~ Nr~
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: '~ 2 5 4 -CF3 4-Cl N Me OEt 4-C1 4-Cl H Me OEt i 4-Br 4-Cl H Me OEt .'. 4-OCF3 4-Cl H Me OEt 4-OC~2N 4-Cl H Me OEt 3'4-CH2C(Me)2O 4-Cl H Me OEt 4-CF3 4-F H Me OEt ~` 4-C1 4-F H Me OEt 4-Er 4-F H Me OEt 4-OC~3 4-F H Me OEt 4-ocr2~ 4-F H lle OEt 3S 3,4-CH2C~Me)20 4-F H Me OEt . ' :
'''' ' ' 2~ 30 Rl R2 k3 R8 R9 4-CF 4-OCF2H H Me OEt 4-C1 4-OCF2H ~ Me OEt ~-8r 4-OCF2H H Me OEt ~: ~-OCF3 ~-OCF2H ~ Me OEt 4-OCF2H ~-OCF2H B Me OEt 3,4-CH2C~Me)20 4-OCF HB Me OEt 4-CF3 4-Br H Me OEt 4-CF3 4-C1 4-Cl Me OEt 4-C~ 4-C1 4-Cl Me OEt 4-Br 4-C1 4-Cl Me OEt : 15 4-OCF3 4-C1 4-Cl Me OEt :` 4-OCF2H 4-C1 4-Cl Me OEt 3,4-CH2C(Me)20 4-C1 4-Cl Me OEt 4-CF3 4-F 4-Cl Me OEt ~- 4-OCF3 4-F 4-Cl Me OEt 4-CF3 4-OCF2H 4-Cl Me OEt 4-OCF3 4-OCF2H 4-Cl Me OEt ~ 4-CF3 4-C1 4-CN Me OEt : :
2 4-C1 4-C1 4-CN Me OEt ,c. 4-OCF3 4-C1 4-CN Me OEt :.
4-CF3 4-F 4-CN Me OEt 4-OCF3 4-F 4-CN Me OEt , 4-CF3 .4-C1 4-CO2MeMe OEt 'j` 4-CF3 4-Cl H Me O-n-Bu ~ 4-OCF3 4-Cl H Me O-n-8u '' 30 4-CF3 4-F H Me O-n-8u : 4-OCF3 4-F H ~e O-n-Hu ;: .
:~ 3,4-CH2C(Me)20 4-F H Me O-n-Bu :.
; 4-CF3 4-OCF2H H he O-J-Bu : 4-C1 4-OCF2H B Me O-n-8u ~ .
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4-CF3 4-Br H M~ O-n-Bu 4-CF3 4-C1 4-Cl Me O-n-Bu 4-C1 4-C1 4-Cl Me O-n-Bu 4-Br 4-C1 4-Cl Me O-n-Bu 4-OCF3 ~-Cl ~-Cl Me O-u-Bu 4-CF3 4-F d-Cl Me O-n-Bu 4-OCF3 4-F 4-Cl Me O-n-Bu 4-CF3 4-OCF2R 4-Cl Me O-n-Bu 4-C1 4-OCF2N 4-CI Me O-n-Bu 4-Br 4-OCF2H 4-Cl Me O_~-Bu 4-OCF3 4-OCF2H 4-Cl Me O-n-Bu 4-CF3 4-C1 4-CN Me O-D-BU
- 4-OCF3 4-C1 4-CN Me O-D-Bu ~- 4-CF3 4-F 4-CN Me O-n-Bu .. 20 4-OCF3 4-F 4-CN Me O-n-Bu 4-C1 4-C02Me Me O-n-Bu 4-CF3 4-OMe 4-Cl Me O-n-Bu 4-C1 4-OPh 4-Cl Me O-n-Bu 4-Br 4-SCF H 4-Cl Me O-n-Bu 4^0CF3 4-N02 4-Cl Me O-n-Bu 4-OCF2~ 4-5Me 4-Cl Me O-n-Bu ~ 3,4-CH2C(Me)20 4-S02Me 4-Cl Me O-n-Bu .,. 4-CF3 4-CN 4-Cl Me O n-Bu - 4-Cl - 3-C1 4-Cl Me O-n-Bu ,~
4-Br 3-F 4-CI Me O-n-Bu ; 4-OCF3 4-Me 4-Cl Me. O-n-~u 4-OCF2H 4-allyl 4-Cl ~e O-D-~U
2 ( )2 4-CF3 4-Cl Me O-n-Bu ;' 4-CF3 -Cl 4-C02Et ~e O-~-Bu '' ' -, .
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2~(~()130 Rl R2 R3 R8 Rg 4-Cl q-Cl ~-aMe Me O-n-Bu 4-Br 4-C1 4 SCF2CF2H Me O-n-Bu '-4-OCF3 4-Cl ~ CF2CF2H Me O-n-~u 4-OCF2H 4-Cl ~-OPh Me O-n-Bu 3~4-cN2c(Me)2o 4-CF3 q-CF3 Me O-n-}3u 4-CF3 4-C1 4-CF3 Me O-n-Bu 4-C1 4-C1 4-Me Me .O-n-Bu 4-Br 4-C1 3-Cl Me O-D-Bu 4-OCF3 4-C1 3-~r ~e O-D-Bu 4-OCF2H 4-C1 4-NO2 Me O-n-~u 4-CF3 4-Cl H Me O-n-hexyl 4-CF3 4-F H Me O-n-he~yl 4-CF 4-OCF2H H Me O-n-he~yl 4-OCF3 4-OCF2N H Me O-n-octyl 4-CF3 4-Br R Me O-n-octyl 4-CF3 4-C1 4-Cl Me O-n-octyl 4-Cl .4-C1 4-Cl Me O-n-octyl 4-}3r 4-C1 4-Cl Me O-n-octyl 4-OCF3 4-C1 4-Cl Me O-n-octyl . --4-CF3 4-F 4-Cl Me O-n-decyl -4-C1 4-F 4-Cl Me O-n-decyl . -4-OCF3 4-F 4-Cl Me O-n-decyl 4-CF3 4-OCF2H 4-Cl Me O-n-decyl .: 4-OCF3 4-OCF2H 4-Cl Me O-n-decyl ~::
,~ 30 4 C 3 4-C1 4-CN Me O-n-decyl . 4-C1 4-C1 4-CN Me O-n-~eeyl 4-Br 4-Cl 4-CN Me O-n-decyl 4-OCF3 4-C1 4-CN Me O-n-dodecyl 4-CF3 ~-r 4-CN Me O-n-dodecyl 4 3 4-r 4-CN Me O-D-dOdeCY1 ~-CF3 4-Cl 9-CO2Me Me O-n-dodecyl 4-CF3 4-Cl H Me O-sec-Bu 4-C1 4-Cl N Me O-sec-Bu ; .
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~42 Rl R2 ~3 R8 Rg 4-OCF3 q-Cl ~ Me O-c~c-Bu 3 4-~ H Me O-sec-Bu 4-OCF3 4-r ~ Me O-cec-Bu 4-CF3 4-OCF2H H Me O-c~c-Bu 4-OCF3 ~-OCF2H ~I Me O-cec-~u 4-CF3 4-9r H Me O-sec-8u 4-CF3 4-Cl ~-Cl Me O-~ec-Bu 4-C1 4-C1 4-Cl Me O-cec-~u ~ 4-Br 4-C1 4-Cl Me 0-6ec-Bu : 4-OCF3 4-C1 4-Cl Me O-cec-Bu 4-CF3 4-F 4-Cl Me 0-6ec-Bu 4-C1 4-F 4-Cl Me O-oec-Bu 4-OCF3 4-F 4-Cl Me O-cec-Bu 4-CF3 4-OCF2H 4-Cl Me O-~ec-Bu .~ 4-OCF3 4-OCF2H 4-Cl Me O-sec-Bu.
~, 20 4-CF3 4-C1 4-CN Me 0-6ec-Bu : 4-C1 4-C1 4-CN Me O-Lec-Bu 4-OCF3 4-C1 4-CN Me O-~ec-Bu 4-CF3 4-F 4-CN Me O-~ec-Bu 4-OCF3 4-F 4-CN ~e O-~ec-Bu '` 25 4-CF3 4-C1 4-C02Me Me O-eec-Bu 4-CF3 4-CN 4-Cl Mc O-sec-Bu .; 4-C1 3-C1 4-Cl Me 0-6ec-Bu " 4-Br 3-F 4-CI Me O-~ec-Bu , 4-OC~3 ~-~e 4-Cl Me O-~ec-Bu 4-CF3 4-C1 4-CO2~t Me O-~ec-Bu ~` 30 4-C1 4-Cl q-OMe Me O-~ec-~u 4-9r 4-C1 2 2 O-sec-Bu ~ 4-OCF3 4-CI ~-Cr2cF2H Me O-rec-Bu " 4-OCF2 4-C1 4-OPh Me O---c-~u 3,4-CH C(Me) O 4-C1 6-CF3 Me O-~oc-Pu , 4 CF3 4-C1 4-CF3 Ue O-cec-Bu 4-C1 4-C1 4-Me Me O-cec-Bu , ~ ' ,: ' ., .~
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4--Br 4-Cl ~-Cl Me O--ec-Bu 4-OCF3 4-C1 3-Br Me O-cec-Bu 4-OCF2H 4-Cl ~-NOz Me O-sec-Bu 4-CF3 ~-Cl H ~e O-~Pr . 4-OCF3 4-Cl H Me O-~Pr :~ 10 4-CF3 4-F H Me O-~Pr 4-OCF3 4-F H Me O-iPr ; 4-CF3 4-OCF2H H Me O-iPr ~ 4-OCF3 4-OCF2H H Me O-iPr : 4-CF3 4-Br H Me O-lPr 4-OCF3 4-Br H Me O-iPr 4-CF 4-C1 4-Cl Me O-iPr - 4-OCF3 4-C1 4-Cl Me O-iPr ~-4-CF3 4-F 4-Cl Me O-~Pr , ~
4-OCF3 4-F 4-Cl Me O-lPr ' ~:
4-CF3 4-Cl q-CN Me O-iPr 4-OCF3 4-C1 4-CN. Me O-~Pr 4-CF3 4-F 4-CN Me O-iPr `~
4-OCF3 4-F 4-CN Me O-iPr ' 25 4-CF3 4-C1 4-CO2MeMe O-~Pr ;, 4-CF3 4-Cl N Me OCH2CH20Et 4-CF 4-F H ~e 2 Z
4-CF 4-OCF2H H Me 2 2 : 4-OCF3 4-OCF2H H Me OCH2ccl3 3 ~-Br H Me OCH2ccl3 4-~F3 q-CI q-Cl Me OCH2CCl 4-C1 4-C1 6-Sl Me OCH2ccl3 : 4-OCF3 ~-Cl 4-Cl Me OCH2ccl3 .~ 4-CF3 4-F 4-Cl Me OCH2CF3 ., 4-OCF3 ~-F 4-Cl . 2 3 4-CF3 4-OCF2H 9-Cl ~e :
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4-Cl ~-Cl B Me F
4-OCF3 4-Cl R Me F
: 4-CF3 4-F ~ Me F
4-OCF3 4-F H Me F
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4-OCF3 4-OCF2N H Me NMe2 4-CF3 4-Br H Me NMe2 ~` 20 4-CF3 4-C1 4-Cl Me NMe2 4-C1 4-C1 4-Cl Me NMe2 :~: 4-OCF3 4-C1 4-Cl Me MMe2 4-CF3 4-F 4-Cl Me NEt2 ~-OCF3 4-F 4-Cl Me NEt ' 25 4-CF3 4-OCF2H 4-Cl Me piperidino .i 4-OCF3 4-OCF2N 4-Cl Me morpholl~o 4-CF3 4-C1 4-CN Me n-Pr 4-OCF3 4-C1 4-CN Me n-Pr . 4-CF3 4-F 4-CN Me Sec-Bu " 4-OCF ~-F 4-CN Me 4-Cl-Pb .~ ~-CF3 4-Cl ~-CO2Me Me Ph ~- 4-CF3 4-Cl H Et O-iPr ~-Cl 4-Cl H Et O-~Pr 4-OÇF3 4-Cl N Et O-lPr 4-ÇF3 4-F H Et O-lPr ~-OCF3 4-F H Et O-~Pr 4-CF3 ~-OCF2N H Et O-~Pr ' ~ ' .
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4-OCF3 A-OCF2H H Et O-~Pr 4-CF3 ~-Br H ~t O-iPr 4-CF3 4-Cl . 4-Cl Et - O-~Pr 4-OCF3 4-C1 4-Cl Et O-~Pr 4-CF3 4-~ q-Cl Et OEt : 4-OCF3 4-F 4-Cl ~t OEt . 4-CF3 4-OCF2H 4-Cl Et ocH2ccl3 ~
: 4-OCF3 4-OCF2H 4-CI Bt 2 4-CF3 4-Cl 4-CN Et 2,6-~i-Me-morpholino 4-OCF3 4-C1 4-CN Et 2,6-di-Me-morpholino 4-CF3 4-F 4-CN Et iPr 4-OCF3 4-F 4-CN Et Ph 3,4-CH2C(Me)20 4-F 4-CN Et Ph - 4-CF3 4-Cl H lPr OEt .
~0 4-OCF3 4-Cl H iPr OEt 4-CF3 4-F H lPr OEt ~ 4-CF3 4-OCF2H H iPr OEt .
; 4-OCF3 4-OCF2H H lPr OEt . 4-CF3 4-Br H iPr OEt : 25 4-CF3 4-C1 4-Cl ~Pr OEt .~ 4-C1 4-C1 4-Cl iPr OEt 4-Br 4-C1 4-Cl iPr OEt 4-OCF3 4-C1 4-Cl iPr OEt !:.
j 4-CF3 4-E 4-Cl iPr OEt 30 4-OCF3 4-F q-Cl iPr OEt ,:
4-CF3 4-OCF2H 4-Cl iPr OEt 4-OCF3 4-OCF2~ 4-Cl iPr OEt . 4-CF3 4-C1 4-CN lPr OEt .:
4-OCF3 4-C1 4-CN lPr OEt 4-CF3 4-F 4-CN lPr OEt ~';"' ,' ':
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.- 20 4-C~3 4-C1 4-CF3 iPr OEt ~ 4-Br 4-C1 3-Cl iPr OEt .. 4-OCF3 4-C1 3-Br iPr OEt ~ 4-OCF2H 4-C1 4-No2 iPr OEt .; 4-CF3 4-Cl H lPr O-n-Bu 25 4-C1 4-Cl H iPr O-n-Bu :~ 4-Br 4-Cl N iPr O-n-Bu 4-OCF3 4-Cl H iPr O-n-Bu ` 4-CF3 4-F H iPr O-n-Bu 4-OCF3 . 4-F H iPr O-n-Bu 4-C~3 4-OCF2H H iPr O-D-Bu ': 30 4-OCF3 4-OCF2H H i~r O-n-Bu ~-CF3 4-Br H iPr O-n-Bu 4-CF3 4-C1 4-Cl iPr O-n-Bu 4-Br 4-C1 4-Cl iPr O-n-0u 4-OCF3 4-C1 4-Cl iPr O-n-Bu 4-CF3 4-F 4-Cl iPr OCH2CF
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4-CF3 4-C14-CN lPr 2 10 4-OCF3 4-C14-CN lPr 2 4-CF3 4-F 4-CN iPrpiperidino 4-OCF3 4-r 4-CN lPr Et 4-CF3 4-C1 4-CO2Me lPr Ph 3,4-CH2C(Me)2O 4-C1 4-CO2Me lPr Ph ; 15 4-CF3 4-Cl H CH2Ph OEt 4-CF3 4-OCF2H H CHzPh piperidiDo .; 4-CF3 4-~r H CH Ph OCH2CH2OEt : 4-CF3 4-C1 4-Cl CH2Ph Me . ,. .: .
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3'4-CH2C(Me)2~ ~-Cl H Me 2 . 4-CF3 ~-F H Me 2 ~ 4-OCF3 4-F H Me 2 " 20 4-CF3 4-DCF2H H Me 4-OCF3 ~-DCF2H ~ Me NEt `' 9-CF ~-~r H Me 2 3,4-CH2C(Me)20 4-~3r H Me NEt2 4-CF3 4-S1 4-Cl Me 2 4-C1 4-D~ 4-Cl Me 2 ~! 4-Br 4-C~ 4-Cl MeNEt2 - 4-OCF3 4-C1 4-Cl Me 2 4-CF3 4-r 4-Cl MeNEt2 9-OCF3 44F 4-Cl Me NEt 4-OCF2H 4-Cl Me NEt 4-OCF3 4-~CF2H 4-Cl Me 4-OCF2N ~-DCF2H 4-Cl Me NEt2 3,4-CH2C~Me)20 ~-~CF2H 4-Cl Me 2 4-CF3 4-C1 4-CN Me NEt2 , 35 3 4_Cl 4-CN Me ~Et2 .~ :
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.,~, 2l~;~P0~30 Rl R2 R3 R8 R9 4-CF 4-F 4-CN Me 2 4-OCF3 4-F 4-CN Me NEt2 4-CF3 4-Cl H Me piperidino 4-OCF3 4-Cl H Me piperidiDo 4-CF3 4-F H Me Se~-Bu 4-OCF3 4-F H Me n-he~yl 4-CF 4-OCF2H H Me Ph ; 4-OCF3 4-OCF2H H Me Ph ` 15 4-CF3 4-Br H Me 4-Cl-Ph 4-C1 4-Br H Me 4-Cl-Ph 4-CF3 4-C1 4-Cl Me n-Bu 4-Cl 4-C1 4-Cl Me n-Bu 4-Br 4-C1 4-Cl Me n-Bu 4-OCF3 4-C1 4-Cl Me n-Bu 4-CF 4-F 4-Cl Et 2 : 4-OCF3 4-F 4-Cl Et 2 .:
4-CF3 4-OCF2H 4-Cl Et NEt2 4-OCF3 4-OCF2H 4-Cl Et morpholino 4-CF3 4-C1 4-CN Et lPr :
3,4-CH2C~Me)2O 4-C1 4-CN Et n-Bu ~ 4-CF3 4-F 4-CN Et n-Bu `
'; 4-CF 4-C1 2 4-MeO-Ph 4 CF 4-Cl H iPr 2 ` 30 4-C1 4-Cl H iPr NMe2 4-Br 4-Cl~ H iPr NMe2 4-oCF3 4-Cl H iPr NMe2 ` 4-CF 4-F H ~Pr NMe2 4-OCF3 4-F H ~Pr 2 4-CF3 4-OCF2H H iPr NMe2 4-OCF3 4-OCF2H H . iPr 2 '' ' ' ,:' :
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; 4-C1 4-C1 4-Cl iPr NMe2 1~ 4-Br 4-C1 4-Cl iPr NMe2 4-OCF3 4-C1 4-CI lPr 2 4-CF 4-F 4-Cl ~Pr 2 :
4-OCF3 4-F 4-Cl iPr 2 4-CF3 4-OCF2H 4-Cl iPr 2,6-di-Me-morpholino : 15 4-OCF3 4-OCF2H 4-Cl iPr piperidino :
4-CF3 4-C1 4-CN iPr Et .,~ 4-OCF3 4-C1 4-CN iPr Et - 4-CF3 4-F 4-CN iPr n-Bu 4-OCF3 4-F 4-CN iPr Ph ' 4-CF3 4-C1 4-CO2Me iPr 4-Cl-Ph ' ~- .
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q~3 0 1 R2 R3 R8 yl YlR1o Y Rll 4-OCF3 4-OCF2H 4-Cl tBu S OEt OEt 4-CF3 4-C1 4-CN tBu S OEt OEt 4-OCF3 4-C1 4-CN tBu S OEt OEt 4-CF3 4-F 4-CN tBu S OEt OEt 4-OCF3 4-F 4-CN tBu S OEt OEt 4-CF3 4-C1 4-CO2Me t8u S OEt OEt 4-CF3 4-Cl H tBu S OCH2C(Me)2CH2O
4-OCF3 4-Cl H t~u S OCH2C(Me)2CH2O
4-CF3 4-F. H tBu S OCH2C(Me)2CH2O
4-C1 4-F H tBu S OCH2C(Me)2CH2O
4-OCF3 4-F H tBu S OCH2c~Me)2cH2O
~-CF3 q-OCF2H H tBu S OCH2C(Me)2CH2O
4-oCF3 4-OCF2H H tBu S OCH2C(Me)2CH2O
4-CF3 4-Br H tBu S OCH2C(Me)2CH2O
4-CF3 4-C1 4-Cl tBu S OCH2C(Me)2CH2O
4-C1 4-C1 4-Cl tBu S OCN2C(Me)2CH2O
4-Br 4-C1 4-Cl tBu S OCH2C(Me)2CH2O
4-OCF3 4-C1 4-Cl tBu S OCH2C(Me)2CH2O
4-CF3 4-F 4-Cl tBu S OCH2C(Me)2CH2O
4-OCF3 4-F 4-Cl tBu S OCH2C(Me)2CH2O
4-CF3 4-OCF2H 4-Cl tBu S OCH2C(Me)2CH2O
4-OCF3 2 tBu S OCH2C(Me)2CH2O
4-CF3 4-C1 4-CN tBu S OCH2C(Me)2CH2O
4-OCF3 4-C1 4-CN tBu S OCH2C(Me)2CH2O
4-CF3 4-F 4-CN tBu S OCB2C(Me)2CH2O
30 4-OCF3 4-F 4-CN tEu S OCH2C(Me)2CH2O
4-CF3 4-C1 4-CO2Me tBu 2 ( )2 2 4-CF3 4-Cl H iPr S OEt OEt 4-C1 4-Cl H iPr S OEt OEt 4-OCF3 4-Cl H ~Pr S OEt OEt 4-CF3 4-F H iPr S OEt OEt 4-OCF3 4-F H iPr S OEt OEt ' , ' .'`, , .
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4-OCF2H H iPr ~ OEt OEt 4-OCF3 4-OCF2H H iPr S OEt OEt 4-C~3 4-Br H ~Pr S OEt OEt 4-CF3 4-C1 4-Cl iPr S OEt OEt 4-OCF3 4-C1 4-Cl iPr S OEt OEt 4-CF3 4-F 4-Cl iPr S OEt OEt 4-OCF3 4 F 4-Cl iPr S OEt OEt q-CF 4-OCF2H 4-Cl iPr S OEt OEt 4-OCF3 4-OCF2H 4-Cl iPr S OEt OEt .~ 4-CF3 4-C1 4-CN iPr S OEt OEt 4-OCF3 4-C1 4-CN iPr S OEt OEt 4-CF3 4-F 4-CN iPr S OEt OEt " 4-OCF3 4-F 4-CN iPr S OEt OEt 4-CF3 4-C1 4-CO2Me iPr S OEt OEt : 20 4-CF3 4-Cl H iPr S OCH2C(Me)2CH2O
. 4-OCF3 4-Cl ~ iPr S OCH2C(Me)2CH2O
, 4-CF3 4-F H iPr S OCH2C(Me)2CH2O
4-OCF3 4-F H iPr S OCH2C(Me)2CH2O
:
," ',:
. . .
~ 30 ~ ~ . ' ' ' .' .
~! `
' ~.
.
. :- ' Z~C~()130 4-CF3 4-OCF2H H iPr S OCH2C(Me)2CH20 .
4-CF3 4-Br H iPr S OCH2C(Me)2CH20 4-CF 4-C1 4-Cl iPr S OCH2C(Me)2CH20 4-C1 4-C1 4-Cl iPr S OCH2C(Me)2CH20 4-Br 4-C1 4-Cl iPr S OCH2C~Me)2CH20 4-OCF3 4-C1 4-Cl iPr S OCH2C(Me)2CH20 4-OCF2H 4-C1 4-Cl iPr S OCH2C(Me)2CH20 4-CF3 4-F 4-Cl iPr S OCH2C(Me)2CH20 . 4-Br 4-F 4-Cl iPr S OCH2C(Me)2CH20 . 4-OCF3 4-F 4-Cl iPr S OCH2C(Me)2CH20 - 4-CF3 4-OCF2H 4-Cl iPr S OCH2C(Me)2CH20 :~ 4-oCF3 2 iPr S OCH2C(Me)2CH20 : 15 4-CF3 4-Cl 4-CN iPr S OCH2C(Me)2CH20 4-OCF3 4-C1 4-CN iPr S OCH C(Me) CH O
v 4-CF3 4-F 4-CN iPr S OCH2C(Me)2CH20 4-OCF3. 4-F 4-CN iPr S OCH2C(Me)2CH20 -CF3 4-C1 4-CO2Me iPr S OCH2C(Me)2CH20 . . 2 D 4-CE3 4-Cl H tBu S OiPr OiPr 4-CF3 4-F H tBu S OiPr OiPr 4-CF3 4-OCF2H H tBu S OCH2CH2CH20 4-OCF3 4-OCF2H H tBu S OCH2CH2CH20 4-CF3 4-Br H tBu S CH2cH2cH2 4-CF3 4-C1 4-Cl tBu S OCH2CH20 , 4-~r 4-C1 4-Cl t8u S OCB2CH20 .~, 4-OCF3 4-C1 4-Cl tBu S CH2c~2 . 4-CF3 4-F 4-Cl Me S OEt OEt 4-OCF3 4-F 4-Cl Me S OEt OEt ~ .
4-CF3 4-OCF2H 4-Cl Me S OEt OEt 4-C1 4-OCF2H 4-Cl Me S OEt OEt .. 4-CF3 4-F 4-CN tBu O OEt OEt ~' 4-OCF3 4-F 4-CN tBu O OEt OEt 4-CF3 4-C1 2 2 ( )2CH2 ,', `
., .
"
: : ~ : .
.~
2~ 013~
~able 19 5 .
.
R2~R3 ; N ~
}R1 ~ -P -YlR~l : R8 Rl o : ' .
.
.~ Rl R2 R3 R8 yl Rlo ylR
v ; 4-CF3 4-Cl H iPr O Et OEt ,. 4-OCF3 4-Cl N iPr O Et OEt : 25 4-CF3 4-F N iPr O Et OEt ; 4-OCF3 4-F H iPr O Et OEt :' 4-CF3 4-OCF2H H iPr O Et OEt '' 4-OCF 4-OCF H H iPr O Et OEt . 3 2 -; 4-CF3 4-Br H iPr O Et OEt . .
~ ~ 4-CF3 4-C1 4-Cl iPr O Et OEt '~ 4-C1 4-C1 4-Cl iPr O Et OEt 4-i3r 4-C1 4-Cl iPr O Et OEt ~' 4-OCF3 4-C1 4-Cl iPr O Et OEt ~- 4-OCF2H 4-C1 4-Cl iPr O Et OEt 4-CF3 4-F 4-Cl iPr O Et OEt 4-C1 4-F 4-Cl iPr O Et OEt 4-Er 4-F 4-CI iPr O Et OEt .., , ' ,:
Z~C~C~130 R1 R2 R3 ~ R8 yl Rlo ylR
i-oCF3 4-F 4-Cl iPr O Et OEt 4-CF3 4-OCF2H 4-Cl iPr O Et OEt 4-OCF3 9-OCF2H 4-Cl iPr O Et OEt 4-CF3 4-C1 4-CN iPr O Et OEt 4-OCF3 4-C1 4-CN iPr O Et OEt 4-C~3 4-F 4-CN iPr O Et OEt 4-OCF3 4-r 4-CN iPr O St OEt 4-C~3 4-C1 4-CO2MelPr O Et OEt 4-CF3 4-Cl H iPr O Et OiPr 4-OCF3 4-Cl H iPr O Et OiPr 4-CF3 4-F H iPr O Et OiPr 4-OCF3 4-F H iPr O Et OiPr 4-CF3 4-OCF2H H iPr O Et OiPr 4-OCF3 4-OCF2H ~ iPr O Et OPh : .
4-OCF2H 4-OCF2H H iPr O Et OPh 3,4-CH2C(Me)2O 4-OCF2H H iPr O Et OPh 4-CF3 4-Br H iPr O Et OPh 4-CF3 4-C1 4-Cl iPr O Et OPh 4-C1 4-C1 4-Cl iPr O Et OPh 4-Br 4-C1 4-Cl lPr O Et OPh 4-OCF3 4-C1 4-Cl iPr O Et OPh 4-OC~2H 4-C1 4-Cl iPr O Et OPh 4-CF3 4-F 4-CN tBu O Et OEt 4-OCF3 4-F 4-CN tBu O Et OEt 4-CF3 4-C1 4-CO2MetBu O Et OEt 4-CF 4-Cl H tBu O Et OiPr 4-OCF3 4-Cl H tBu O Et OiPr 4-CF3 4-F H tBu O Et OiPr 4-OCF3 4-F H tHu O Et OiPr q-cF3 4-OCF2H H tBu O Et OiPr 4-OCF3 4-OCF2H N Ph O Et OEt '.
. ,.
':~
,!
Z~ 3~
.~ .
. R2 R3 R8 yl Rlo YlR
4-CF3 9-F H iPr S Et OEt 4-OCF3 4-F H iPr S Ph OEt 4-CF 4-OCF2H 4-Cl tBu S Et OEt 4-OC~3 4-OCF2H 4-Cl tEu S Ph OEt . 4-CF3 9-F 4-CN iPr S iPr OiPr . 10 4-OCF3 4-F 4-CN iPr S nPr OEt 4-CF3 4-C1 4-CO2Me tBu S Me OEt . ,.
,~ 15 ::
.' . .
!i ''~ ,, .``~
' 25 .``' ,' ', -.. . .
.,, j . : .
.` 30 ~ ` , .
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~ 35 ~ .
-,, ..-..
2~QQ13~) .
:~ ~able 2~
.' ~, " .
R~
~ ~ R1 S
."
..
R1 R2 _ 3 Rg :-, 4-CF3 4-Cl H CF
~ 4-CF3 4-F 3 '~! 25 4-CF34-OCF2H H CF3 " 4 CF 4-Br H CF3 ,i. 4-CF3 4-Cl 4-Cl 3 4-Cl 4-Cl 4-Cl CF3 .. 30 4-Cl 4-Cl 3 : 4-OCF3 4-C1 4-Cl 3 4-OCF2H 4-Cl 4-Cl 3 ~: .
' 3,4-CH2C(Me)2O ~-Cl 4-Cl 3 -:: 4-CF3 4-F 4-ClCF3 3 4-OCF2H 4-Cl 3 4-CF 4-Cl 4-CN 3 ." .
.,~ . .
.
, ~ . .
3~
. . .
Rl R2 R3 R9 4-CF3 4-C1 4-C02Me CF3 4-CF3 4-Cl H O-~ecBu 4-CF3 4-F ' H 0-6ecBu 4-CF 4-OCF2H H 0-6ecBu 4-C1 4-OCF2H H O-~ecBu ;~ 4-OCF3 4-OCF2H H O-secBu '~
:~ 4-CF3 4-Br H 0-6ecBu 4-CF3 4-C1 4-C1 0-8ecBu 4-C1 4-C1 4-C1 O-secBu : 15 4-Br 4-C1 4-C1 O-secBu 4-OCF3 4-C1 4-C1 0-8ecBu ~: 4-CF3 4-F 4-C1 0-6ecBu 4-C1 4-F 4-C1 0-6ecBu 4-OCF3 4-F 4-C1 0-6ecBu .` 20 4-CF3 4-OCF2H 4-C1 O-secBu ',',! 4-OCF3 4-OCF2H 4-C1 O-secBu 4-CF3 4-C1 4-CN O-secBu . 4-CF3 4-F 4-CN 0-6ecBu . 4-CF3 4-C1 4-C02Me 0-6ecBu , 25 4-CF3 4-Cl H O-n-Bu . 4-CF3 4-F H O-n-Bu ~` 4-CF3 4-OCF2H H O-n-Bu 4-C1 4-OCF2H H O-n-Bu 4-Hr 4-OCF2B H O-n-Bu : -4~OCF3 4-OCF2H H O-n-Bu `~
4-OCF2H 4-OCF2H H O-n-Bu ~ .
3~4-CH2C~Me)20 4-OCF2H . H O-n-Bu , 4-CF3 4-Br H O-n-Bu ~ ,~
'~ 4-CF3 4-C1 4-Cl O-n-Bu , 4-C1 4-C1 4-Cl O-n-Bu . 4-OCF3 4-C1 4-Cl O-n-Bu :
4-CF3 4-F 4-Cl O-n-hexyl .; ~
:~ :
- . :
', : :
2~100~30 Rl R2 R3 Rg - 5 4-Cl 4-F 4-ClO-n-he~yl 4-OCF3 4-F 4-ClO-n-he~yl 4-CF3 4-OCF2H 4-ClO-n-he~yl 4-CF3 4-C1 4-CNO-D-he~yl 4-CF3 4-F 4-CNO-n-he~yl 4-CF3 4-C1 4-CO2Me O-n-he~yl : 4-CF3 4-OCF2H 2 3 -CF3 4-Br HOCH2CC13 :`
:~ 4-OCF3 4-C1 4-ClOCH2CC13 " 20 4-CF3 4-F 4-ClOCH2CH2OEt 4-CF3 4-OCF2H 4-ClOCH2CH2OEt . 4-CF3 4-C1 4-CNoCH2CH2OEt ~:
4-CF3 4-F 4-CNOCH2CH2OEt :~" 25 4-CF3 4-C1 4-CO2Me OCH2CHzOEt ~;
.
.
.. 30 :,' ~'.' , ~ .
:,. .
,' ' .
. ,. ~ .
:'`'` ' .' .
Z~?00:130 :
Table 21 :
~. .
.~ 10 R2~R3 N ~ ~:
~ ~ R1 . I , .
S -p-ORlo . OR1 ~
:.i . ,. ' .
, ~ -, 20 .~ l R2 R3 Rlo Rll : .
-~ 4-CF3 4-Cl H Et Et j ~' 4-CF3 4-F H Et Et 4-CF3 4-OCF2H H Et Et .
4-CF3 4-Br H Et Et "` .
4-CF3 4-Cl 4-Cl Et Et ,,~ 4-Cl 4-Cl 4-Cl Et Et '~1 4-Br 4-Cl 4-Cl Et Et ~! 4-OCF3 4-Cl 4-Cl Et Et 4-OCF H 4-Cl 4-Cl Et Et 3,4-CH2C~Me)2O 4-C1 4-Cl Et Et '~. 4-CF3 4-F 4-Cl Et Et 4-Cl 4-F 4-Cl Et St 4-Br 4-F 4-Cl Et Et , .', :
.
'.''. '~ , ':
.. ~ .
. . .
7 . i' ~ ~, 2~ 01.. ~0 Rl R2 R3 Rl~ Rll 4--OCF3 4-F 4-Cl ' Et Et 4-OCF2H 4-F 4-Cl Et Et 3,4-CH2C(Me)20 4-F 4-Cl Et Et 4-CF3 4-OCF2H 4-Cl Et Et 4-CF3 4-C1 4-CN Et Et 4-CF3 4-F 4-CN Et Et 4-CF3 4-C1 4-CO2Me Et Et 4-CF 4-Cl H -CH2CH2- .
4-CF 4-9r H -CH2CH2-4-CF3 4-C1 4-Cl-CH2CH2- , 4-C1 4-C1 4-Cl-CH2CH2-4-OCF3 4-C1 4-Cl-CH2CH2-4-CF 4-F 4-Cl-CH2CH2CH2-4-C1 4-F 4-Cl-CH2CH2CH2-4-OCF3 4-F 4-Cl-CH2CH2CH2-q-CF3 4-OCF2H 4-Cl-CH2CH2CH2-4-OCF3 4-OCF2H 4-Cl-CH2CH2CH2-~-CF3 4-F 4-CN2 2 2 3 4-C1 4-CO2Me2 2 2 4-CF3 4-Cl H-CH2C(Me)2CH2-4 CF 4-F 2 ( )2 2 4-CF3 4-OCF2H H-CH2C(Me)2CH2-4-CF3 4-~r ~-CH2C~Me)2CH2-4-CF3 4-C1 4-Cl-CH2C~Me)2CH2-4-C1 4-C1 4-Cl-CH2C~Me)2CH2-4-~r 4-C1 4-Cl-CH2C~Me)2CH2-.
4-OCF3 4-C1 4-Cl-CN2C~Me)2cH2- . ~.
.
,: - .
., ' '.
, . : : - : . . . : : :
Z~)00~30 Rl R2 R3 Rlo R
4-OCF H 4-C1 4-Cl -CH2C(Me)2CH2-3,4-CH2C(Me~2O 4-C1 4-Cl -CH2C(Me~2CH2-4-CF3 4-F 4-Cl. Ph Ph 4-CF 4-OCF2H 4-ClPh Ph 4-CF 4-C1 4-CNPh Ph 0 4-CF3 4-F4-CN Ph Ph 4-CF3 4-C1 4-CO2Me Ph Ph , ...
~
. .
.
., ' ~' ~,`.,.. ' "
, ., .
,' ~, 30 . ., ''' :
. '. ,.
., . .`: - .
~ 35 .' . :
,. . .
.. . .
~\
Zl~C~0~310 Table 22 :~ 5 J~3 B
Re : 15 .,., R-2 ~ .
:`
, :,, .: .
Rl R2 R3 R8R12 ~ 4-CF3 4-Cl H DBunBu :; 4-C1 4-Cl H nBunBu . 4-OCF3 4-Cl H nBuDBu -CF3 4-F H nBuDBu :~-` 5 4-CF3 4-OCF2H H nBunBu -~- 4-OCF3 4-OCF2H H nBunBu .
4-CF3 4-Br H nBunBu . 4-CF3 4-C1 4-Cl nBunBu `~ 4-C1 4-C1 4-Cl ~BuD8U
:~ 30 4-Br 4-C1 4-Cl nBu nBu 4-OCF3 4-C1 4-Cl DBu~Bu ~` 4 CF 4-F 4-C1 22CH2CH2CH2_ ..
4-CF3 4-OCF2H 4-C12CH2~H2C~zCH2_ 4-CF3 4-Cl 4-CN-CH2CH2CH2CH2CH2_ ~ 35 4-CF3 4-F 4-CN-CH2CH2CH2CH2C~2-' ' :
'~ ;'............................................................ ',',' - \
4-CF 4-C1 4-CO2Me -CH2CH2CH2CH2CH2-4-CF3 4-Cl H -CH2CH20CH2CH2- ..
4-OCF3 4-Cl H 2 2 2 2 4-CF 4-F . H -CH2CH20CH2CH2-4-CF3 4-OCF2H H -CH2CH20CH2CH2- ~, 4-OCF3 4-OCF2H H -CH2CH20CH2cH2~
4-CF3 4-Br H -CH2cH2c82cH2-4 C 4-C1 4-Cl -CH2CH20CH2CH2- ..
4-C1 4-C~ 4-Cl -CH2CH20CH2CH2-4-Br 4-Cl 4-Cl -CH2CH20CH2CH2-: 9-OCF3 4-C1 4-Cl -CH2CH20CH2CH2-4-CF 4-F 4-Cl -CH2CHMeOCBMeCH2-4-CF 4-OCF2H 4-Cl -CH2CHMeOCHMeCH2-4-CF3 4-C1 4-CN -CH2CHMeOCHMeCH2- . :
4-CF3 4-F 4-CN -CH2CHMeOCHMeCH2-4-CF3 4-C1 4-CO2Me -CH2CHMeOCHMeCH2-4-CF 4-Cl H Et c ~, 4-CF3 4-F H Et cyclo-C6H
~; 4 CF 4-OCF2H H Et c ". 25 4-CF3 4-Br ~ Et c ~` 4-C1 4-Cl Et c - 4-C1 4-C1 4-Cl Et c .~ 4-Fr 4-C1 4-Cl Et cyClo-c6 . 4-OCF3 4-C1 4-Cl Et c ; 4-CF3 4-F 4-Cl iPr -CH2CH2CO2ET
4-C1 4-F 4-Cl iPr -CH2cH2c2ET
.~ 4-OCF3 4-F 4-Cl iPr -CH2cH2c2ET
3 4-OCF2H 4-Cl iPr -CH2cH2c2ET
4-C1 4-OCF2B 4-Cl iPr -CH2CH2C02ST
4-Br 4-OCF2H 4-Cl iPr -CH2cH2c2~T
.. 35 q-OCF3 2 iPr -CH2CH2CO2ET
,' ' . ~
~ :
.. ...
.'' '"'~'~
.:- : : : , ' ' : . . : : -,, : :''"',''. ',' ' ' '' '."'' ':',' ' ' 2l~0(~`13(;~
Rl R2 R3 R8 R12 4~OCF2H 4-OCF2H 4-Cl lPr -CH2CH2C02ET
3,4-CH2C(Me)2O 4-OCF2H 4-Cl iPr -CH2CH2CO2ET
4-CF3 4-C1 4-CN iPr -CH2CH2CO2ET
4-C1 4-C1 4-CN iPr -CH2CH2CO2ET
4-OCF3 4-C1 4-CN CF3 . 2,4-di-Cl-Ph 4-CF3 4-F 4-CN CF3 2,4-di-Ci-Ph 4-CF 4-C1 2 3 2,4-di-Cl-Ph : 15 .~ .
','', :
~ 20 .
'~, : 25 ~` ''.
. ~ .
:; 30 .~`i ,:
~ 35 :
:
,:, - ~ . - , . -: . : . .: : : :
Z'~ ~0~30 ~j~
Table 23 Rz ~ R3 o~uJ~
S~R10 ','' ' .. ...
~'< ';'' ' , 20 ` Rl R2 R3 R10 .j.` 4-CF3 4-Cl H tBu 4-OC~ 4-Cl H tBu .~ 25 4-CF3 4-F H tBu ~"3 4-CF3 4-OCF2H H tBu ~ 4-OCF3 4-OCF2H H tBu .~: 4-CF3 4-Br H tBu ' 4-CF3 4-C1 4-Cl tBu : 30 4-C1 4-C1 4-Cl tBu ................ 4-Br 4-C1 4-Cl tBu 4-OCF3 4-C1 4-CI tBu " 4-OCF2N 4-C1 4-Cl tFu .'; 4-CF3 4-~ 4-Cl tBu 4-CF3 4-OCF2H 4-Cl tBu . , ,' ., .
' ' Z~ 'Pl3~ ' Rl R2 R3 Rlo _ _ . .
5 i-Cl 4-OCF2H 4-Cl tBu 4-OCF3 4-OCF2H 4-Cl tBu 4-CF3 4-C1 4-CN tBu 4-CF3 4-F 4-CN tBu 4-CF3 4-C1 4-CO2Me tBu ~ 10 4-CF3 4-Cl H sec-Fu .: 4-OCF3 4-Cl H ~ec-Bu 4-CF3 ~-F H cec-Fu .- 4-OCF3 4-F H ~ec-Bu : 4-CF 4-OCF2H H ~ec-Bu 4-C1 4-OCF2H H ~ec-8u 4-OCF3 4-OCF2H H Ph , 4-OCF2H 4-OCF2H H Ph 3,4-CH2C(Me)20 4-OCF2H H Ph 4-CF3 4-Br H Ph 4-CF3 4-C1 4-Cl Ph 4-C1 4-C1 4-Cl Ph 4-Br 4-C1 4-Cl Ph 4-OCF3 4-C1 4-Cl - Ph . 4-OCF2H 4-C1 4-Cl Ph - 25 3,4-C82C(Me)20 4-C1 4-Cl Ph 4-CF3 4-F 4-C1 4-Cl-Ph 4-C1 4-F 4-C1 4-Cl-Ph :; 4-Br 4-F 4-C1 4-Cl-Ph 4-oCF3 4-F 4-C1 4-Cl-Ph 4-OCF2H 4-F 4-C1 4-Cl-Ph 3~4-CH2C~Me~20 4-F 4-C1 4-Cl-Ph ; 4-CF3 4-OCF2H 4-C1 4-Cl-Ph 4-CF3 4-Cl 4-CN 4-Cl-Ph ,. 4-OCF3 4-C1 4-CN 2-Me-4-t-Bu-Ph :
.. , 1, ~' 35 ., .
,.' . ' .
'~ ~
. 170 :
; Rl R2 R3 Rlo 4-CF 4.F 4-CN2-Me-4-t-Bu-Ph ~: 4-OCF3 4-F 4-CN2-Me-4-t-Bu-Ph 4-CF3 4-C1 4-CO2Me2-Me-4-t-Bu-Ph .::
4-CF 4-C1 H2-NO2-Ph 4-OCF3 4-Cl H2-NO2-Ph 4-CF3 4-F H2-NO2-Ph 4-CF3 4-OCF2H H 2-NO2-Ph 4-CF 4-Br H2-NO2-Ph 4-CF3 4-C1 4-C12-N2-Ph 4-Br 4-C1 4-C12-NO2-Ph : 4-OCF3 4-C1 4-C12-NO2-Ph .'. 4-CF3 4-F 4-C12-NO2Ph 4-Cl 4-F 4-C12-NO2Ph q C 4-OCF2H 4-C12-N2Ph 4-OCF3 4-OCF2H 4-C12-NO2Ph 4-CF3 4-C1 4-CN2-NO2Ph 4-OCF3 4-C1 4-CN2-NO2Ph :.` 25 4-CF3 4-F 4-CN2-NO2Ph ~ 4-CF 4-C1 4-CO2Me2-N2Ph ~:
.'', :
... . .
~,. i :.;
:. ' ~5 :~
.. ;
G
2~?0013(:~
Table 24 .
~.
10 ~ 3 fi2 j~
~N
~,Rl ~ .
15 ~ , ." ~,.
: 20 :~. Rl R2 R3 Z
.~` 4-CF3 4-H 4-H CH3 ~- 25 4-CF3 4-H 4-Cl CH3 4-CF3 4-F 4-Cl CH3 . 4-CF3 4-F 4-F CH3 4-CF3 4-C~ 4-Cl CH3 4-C~3 4-Cl 4-F CH3 '~ 4-CF3 4-OCHF2 4-H CH3 4-CF3 4-OCHF2 4-Cl CH3 ~` 4-CF3 4-OCHF2 4-F CH3 ' 35 .
., .
'.~
,j. :
.''. . ~'~.
;.:, . . ... . . . . , , ` ` ~
2;1100~30 172 :.
:: R R2 R3 Z
~. .
4-OCF3 4-H 4-H CH3 ..
4-OCF3 4-R 4-Cl CH3 ~ 4-OCF3 4-F 4-H CH3 .: 10 4-OCF3 4-F 4-Cl CH3 . 4-OCF3 4-F 4-F CH3 .. : 4-OCF3 4-C1 4-Cl CH3 .: 4-OCF3 4-C1 4-F C~3 :~ 15 4-C1 4-H 4-H CH3 :` 4-C1 4-H 4-Cl CH3 . 4-C1 4-H 4-F CH3 .
.~ 4-C~ 4-C1 4-H CH3 :.
4-C1 4-C1 4-Cl CH3 : 20 4-C1 4-C1 4-F CH3 4-C1 4-F 4-Cl CH3 4-C1 4-F 4-F . CH3 " 4-Br 4-H 4-H CH3 4-8r 4-H 4-F CH3 . 4-Br 4-~ 4-Cl CH3 ., 4-Br 4-C1 4-H CH3 . 4-8r 4-C1 4-F CH
4-Er 4-C1 4-Cl CH3 4-Br 4-F 4-H CH3 4-Br 4-F 4-F CH3 4-~3r 4-F 4-Cl CH3 . 4-OCHF2 4-H 4-H C~3 .. 4-OCHF2 4-H 4-F CH3 4-OCHF2 4-H 4-Cl CH3 ;' ~ ~'.
,. ~ . . . - : .: .
0~3Q
. Rl R2 R3 Z
~ .
4-OCHF2 4-F 4-Cl CH3 4-OCHF2 4-Cl 4-H CH3 4-OCHF2 4-C1 4-Cl CH3 4-CF3 4-H 4-Cl CH3CH2 .. 4-CF3 4-F 4-H CH3CHZ
4-CF3 4-F 4-Cl CH3CH2 .
4-CF3 4-C1 4-H C~3CH2 4-CF3 4-C1 4-Cl CH3CH2 . 4-CF3 4-C1 4-F . CH3C~2 4-CF3 4-OCHF2 4-Cl CH3CH2 .. 4-OCF3 4-H 4-H CH3CH2 `. 25 4-OCF3 4-H 4-Cl CH3CH2 .. 4-OCF3 4-H 4-F CH3CH2 ,~ 4-OCF3 4-F 4-H CH3CH2 4-OCF3 4-F 4-Cl CH3CH2 .- 30 4-OCF3 4-C1 4-Cl CH3CH2 4-C~ 4-H 4-H CH3CH2 4-C1 4_~ 4-C1 3CH2 ,` ~
,: . : : ' ':
`, !'''~: "
.. .'.
~ , , - .-. .:. .:: :,.
;~ ~
Z~-~00130 . .
Rl R2 R3 Z
.
- 4-C1 4-C1 4-Cl CH3CH2 : 4-C1 4-C1 4-F CH3 Q2 4-C1 4-F 4-H CH3CH2 , .` 10 4-C1 4-F 4-Cl CH3CH2 4-C1 4-F 4-F CH3CH2 ~:
4-CF3 4-H 4-Cl C6H5 : 4-CF3 4-F 4-Cl C6H5 : q-CF3 4-F 4-F C6H5 4-CF3 4-C1 4-Cl C6H5 . 20 4-CF3 4-C1 4-F C6H5 ~r~ 4-CF3 4-OCHF2 4-H C6H5 ~. 4-CF3 4-OCHF2 4-Cl C6H5 .'i.' 4-CF3 4-OCHF2 4-F C6H5 ~' 25 4-OCF3 4-H 4-H C6H5 ;~ 4-OCF3 4-H 4-Cl C6H5 ~`, 4-OCF3 4-H 4-F C6H5 .
:' 4-OCF3 4-F 4-H C6H5 ' 4-OCF3 4-F 4-Cl C6H5 .. 4-OCF3 4-F 4-F C6H5 3~ 4-OCF3 4-C1 4-H C6H5 .
.-. 4-OCF3 4-C1 4-Cl C6H5 : 4-OCF3 4-C1 4-F C6H5 4-C1 4-H 4-H C6~5 4-C1 4-H 4-Cl C6H5 ~5 4-C1 4-H 4-F C6H5 , '; ' . . ~
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4-C1 4-F 4-Cl C6H5 4-CF3 4-H 4-Cl C~30 4-CF3 4-F 4-Cl CH30 : 15 4-CF3 4-C1 4-H CH30 4-CF3 4-C1 4-Cl CH30 ~ 4-CF3 4-C1 4-F CH30 `; 4-CF3 4-OCHF24-Cl CH30 : 20 4-CF3 4-OCNF24-F CR30 :. 4-OCF3 4-H 4-H CH30 ., 4-OCF3 4-H 4-Cl CH30 4-OCF3 4-F 4-Cl CH30 .` 4-ocr3 4-F 4-F CH30 :' 4-OCF3 4-C1 4-H CH30 .' 4-OCF3 4-C1 4-Cl CH30 ":` 4-OCF3 4-C1 4-F CH30 ~ 4-C1 4-H 4-Cl CH30 .,1 4-C1 4-H 9-F CH30 4-C1 4-C1 4-Cl CH30 ~ . ~
:. :
,:
:-,. , : :
Z~00130 R R2 R3 _ _ _ _ 4-C1 4-F 4-Cl CH30 .
4-CF3 4-H 4-Cl H
4-CF3 4-F 4-Cl H
4-CF3 4-C1 4-Cl H
4-CF3 4-OCHF2 4-H H ~.
4-C~3 4-OCHF2 4-Cl H
4-CF3 4-OCHF2 4-F H .
q-OCF3 4-H 4-H H
4-OCF3 9-H 4-Cl H
4-OCF3 4-F 4-Cl H . :.
4-OCF3 4-C1 4-H H ~.
4-OCF3 4-C1 4-Cl H
4-CI 4-H 4-H .H
4-C1 4-H 4-Cl H
4-C1 4-C1 4-Cl H
., .
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Rl R2 R3 Z
: 5 4-C1 4-F 4-Cl H
-CF3 4-C1 4-Cl BrCH2 10 4-CF3 4-C1 4-Cl ClCH2 9-CF3 4-C1 4-Cl CF3 4-CF3 4-C1 4-Cl benzyl 4-CF3 4-C1 4-Cl CH3CH2CH2 4-CF3 4-C1 4-Cl CH3(CH2)3 lS 4-CF3 4-C1 4-Cl CH3(CH2)4 4-CF3 4-C1 4-Cl CH3(CH2)5 4-CF3 4-C1 4-Cl CH3(CH2)6 4-CF3 4-C1 4-Cl CH3(CH2)7 .
: 4-CF3 4-C1 4-Cl CH3(CH2)9 20 4-CF3 4-C1 4-Cl CH3(CH2)10 4-CF3 4-C1 4-Cl C13C
4-CF3 4-C1 4-Cl i-Pr 4-CF3 4-Cl 4-Cl t-Bu 4-CF3 4-C1 4-Cl MeO2C
-CF3 4-C1 4-Cl EtO2C
4-CF3 4-C1 4-C1 2-Cl-phenyl 4-CF3 4-C1 4-C1 3-Cl-pbenyl 4-CF3 4-C1 4-C1 4-Cl-phenyl , 4-CF3 4-C1 4-Cl CH3CH20 30 4-CF3 4-C1 4-Cl CH3(CH2~20 ` 4-CF3 4-C1 4-Cl CH3(CH2)40 4-CF3 4-C~ 4-Cl CH3(CH2)60 4-CF3 4-C1 4-Cl CH3(CH2)Bo 4-CF3 4-C1 4-Cl CH3(CH2)100 35 4-CF3 4-C1 4-Cl phenyl-0 4-CF3 4-C1 4-C1 4-Cl-pbenyl-0 '~ .
2i~0130 Rl R2 R3 Z
5 .
4-CF3 4-C1 4-Cl benzyl-O
4-C1 4-C1 4-Cl ClCH2 4-C1 4-C1 4-Cl CF3 4-CI 4-C1 4-Cl benzyl 10 4-C1 4-C1 4-Cl CH3~CH2)3 4-C1 4-C1 4-Cl CH32C
4-C1 4-C1 4-Cl CH3CH2O
.~
: 1 5 .
i i'-' 20 `' :,.
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Table `' ' '', ' Rz ~ ~ R3 . N
S~N,L~R
R8 . !
.
. R2 R3 R8 Rg .. 4-CF3 4-Cl H Me O-nBu 4-OCF3 4-Cl H Me O-n9u .~ - 2S 4-CF3 4-F H Me O-nBu ,~. 4-OCF3 4-F H Me O-nBu -CF3 4-OCF2H H Me O-nBu 4-CF3 4-8r H Me O-nBu . 4-CF3 4-Cl 4-Cl Me O-nBu 30 4-Cl 4-Cl 4-Cl Me O-nBu 4-Br 4-Cl 9-Cl Me O-nBu ,. 4-OCF3 4-Cl 4-Cl Me O-nBu 4-CF3 4-F 4-Cl Me O-nBu 4-CF 4-OCF2H 4-Cl Me O-nBu ,` 4-CF3 4-Cl 4-CN Me O-nBu ; 35 .;
:' Z00013(~
Rl R2 R3 R8 Rg :
4-CF3 4-F 4-CN Me O-nBu 4-CF 4-C1 4-C02Me Me O-DEU
4-CF3 4-Cl H Me O-~-he~yl 4-CF3 4-F H Me O-n-hexyl 4-CF3 4-OCF2H N Me O-n-octyl 4-CF3 4-Br 8 Me O-D-decyl 4-CF3 4-C1 4-Cl Me O-n-dodecyl 4-C1 4-C1 4-Cl Me O-n-dodecyl 4-Br 4-C1 4-Cl Me O-n-dodecyl 4-OCF3 4-C1 4-Cl Me O-n-dodecyl 4-CF3 4-F 4-Cl Me O-sec-Bu 4-C1 4-F 4-Cl Me O-sec-Fu 4-Br 4-F 4-Cl Me O-sec-Bu 4-OCF3 4-F 4-Cl Me O-sec-Bu - 4-CF3 4-OCF2N 4-Cl Me 0-6ec-Bu : q-CF3 4-C1 4-CN Me O-iPr .
4-C~3 4-F 4-CN Me OCH2CH20Et `~ 4-C1 4-C02Me Me 2 3 4-CF3 4-Cl H Me F
4-F H Me 2 3 4-OCF2H ~ Me NEtz 4-CF3 4-Br H Me morpholino ,. 4-OCF3 4-Br H Me n-Pr 4-CF3 4-C1 4-Cl Me sec-Bu 4-~r 4-C1 4-Cl Me Ph 4-OCF3 4-C1 4-Cl Me Ph :~ 4-CF3 4-~ 4-Cl Et O-iPr ' 30 4-CF3 4-OCF2H 4-Cl Et O-iPr 4-CF 4-C1 4-CN St OCH2ccl3 i 4-OCF3 4-C1 4-CN Et NEt2 4-CF3 4-F 4-CN Et 2,6-di_~e-~orpholino 4-C1 4-F 4-CN Et 2,6-di-Me-morpholino -CF3 4-C1 4-C02Me Et Ph 4-CF3 4-Cl H iPr OEt 4-CF3 4-F H iPr OEt .
- , . , . - . ~.. - " .-- - . ~ . -- - .. . : :: ~ - : .: : . . : : .. . .
2~Q013() R2 R3 R8 Rg 4-OCF2H H iPr OEt 4-C1 4-OCF2H H iPr OEt 4-Br 4-OCF2H H iPr OEt 4-OCF3 4-OCE2H H iPr OEt 4-OCF2H 4-OCF2H H iPr OEt 3,4-CH2C(Me)20 4-OCF2~ H iPr OEt 4-CF3 4-Br H iPr OEt 9-CF~ 4-C1 4-Cl iPr OEt 4-OCF3 4-C1 4-Cl iPr OEt ~,~ 4-CF3 4-F 4-Cl iPr OEt 4-OCF3 4-F 4-Cl iPr OEt-4-CF 4-OCF2H 4-Cl iPr OEt : 4-OCF3 4-OCF2H 4-Cl iPr OEt . 4-CF3 4-C1 4-CN iPr OEt 4-OCF3 4-C1 4-CN iPr OEt ':~ 20 4-CF3 4-F 4-CN iPr OEt 4-CF3 4-C1 4-CO2Me iPr OEt ., 4-OCF3 4-C1 4-CO2Me iPr OEt ~ 4-CF3 4-OMq 4-Cl iPr OEt i, 4-C1 4-OPh 4-Cl iPr OEt ~ 25 4-Pr 4-SCF2H 4-Cl iPr OEt ,.
4-OCF3 4-No2 4-Cl iPr OEt i 4-OCF2H 4-SMe 4-Cl iPr OEt 3,4-CH2C(Me)20 4-SO2Me 4-Cl iPr OEt 4-CF3 4-CN 4-Cl iPr OEt - 30 4-C1 3-C1 4-Cl iPr OEt 4-Br 3-F 4-Cl iPr OEt ~-OCF3 4-Ne 4-Cl iPr OEt 4-OCF2H 4-0-~llyl 4-Cl iPr OEt 3,4-CH2C(Me)20 4-CF3 4-Cl iPr OEt 4 CF 4-C1 4-CO2Et iPr OEt ; 35 4-C1 4-C1 4-OMe iPr OEt 4-Br 4-C1 4-SCF2CF2H iPr OEt 4-OCF3 4-C1 4-OCF2CF2H iPr OEt Z~00~30 ..
Rl R2 R3 R~ Rg 4-CF 4-C1 4-CF3 iPr OEt : 4-Cl ~-Cl 4-Me iPr OEt 4-Br 4-C1 3-Cl iPr OEt 4-OCF3 4-C1 3-Br iPr OEt 4-OCF2H 4-C1 4-NO2 iPr OEt 4-CF3 4-Cl H iPr O-n-Bu : 10 4-CF3 4-F H iPr O-n-Bu 4-OCF3 4-F ~ iPr OCH2CO2Me 4-CF 4-~CF2H H iPr NMe2 4-OCF3 4-OCF2H H iPr piperidino 3,4-CH2C(Me)20 4-0CF2H H iPr Et 4-CF3 4-Br H iPr Et 4-OCF3 4-Br H CH2Ph OEt 4-CF3 4-Cl 4-CO2Me CH2Ph NME2 . 20 ':~ ' ' ,~ :
~ 25 ', . .
:
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O
: 15 N--S -R9 Ra , 3 -Cl 9 3 4-F H Me 2 4-CF3 4-OCF2H H Me n-hexyl ~ .
4-OCF3 4-OCF2H H Me Ph 4-CF3 4-Br H Me 4-Me-Ph ~ 4-CF3 4-C1 4-Cl Et morpholiDo ;.~ 4-C1 4-C1 4-Cl Et iPr '. 4-Br 4-C1 4-Cl Et n-Bu ::
: 30 4-OCF3 4-C1 4-Cl Et Ph 4-CF 4-F 4-Cl iPr NMe2 4-CF3 2 iPr piperidino 4-C1 4-OCF2H 4-Cl iPr Et :~
4-Br 2 Cl iPr D-Bu . 35 4-OCF3 2 iPr Ph 4-OCF2H 2 Cl iPr 4-Cl-Ph ., '. .
... . .
.' j`'' ' ', ;' ' '' Table 27 Rz ~ ~ R3 N ~
S ~ _p -YlR ;
Re Y R, :
."
R2 R3 R8 yl YlR Y Rll . 4-CF3 4-Cl H tBu S OEt OEt . 4-C1 4-Cl H tBu S OEt OEt 4-Br 4-Cl H tBu S OEt, OEt :~ 25 4-OCF3 4-Cl H tBu S OEt OEt 9-OCF2H 4-Cl H tBu S OEt OEt ;? 3,4-CH2C(Me)2O 4-Cl H tBu S OEt OEt `~ 4-CF3 4-F H tBu S OEt OEt ~ 4-C1 4-F H tBu S OEt OEt t 4-~r 4-F H tBu S OEt OEt 4-OCF 4-F ~ tBu S OCH2C(Me)2CH2O
4-OCF2H 4-F H tBu S OCH2C~Me)2CH2O
3,4-CH2C(Me)2O 4-F H tBu S OCH2C(~e)2CH2O
3 4-OCF2H H tBu S OCH2C(Me)2CH2O
4-C1 4-OCF2H H tBu S OCH2C(Me)2CH2O
4-Br 4-OCF2H H tBu S OCH2C(Me)2CH2O
,, ':
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:-- , . ,,, - ., . - . - , . - - ~ . . .
Zt~ 130 Rl ~2 R3 R8 yl YlR YlR
..
4-OCF3 4-OCF2H H tBu S OCH2C~Me)2CH2O
4-OCF2H 4-OCF2H H tBu S OCH2C(Me)2CH2O
3,4-CH2C(Me)2O 4-OCF2H H tBu S OCH2C(Me)2CH2O
4-CF3 4-Br H tBu S OCH2C(Me)2CH2O
4-C1 4-Br H iPr S OEt OEt : 4-9r 4-Br H iPr S OEt OEt 4-OCF3 4-Br H iPr S OFt OEt 4-OCF2H 4-Br H iPr S OEt OEt 3~4-cH2c(Me)2o 4-Br H iPr S OEt OEt 4-CF3 4-C1 4-CliPr S OEt OEt 4-C1 4-C1 4-CliPr S OEt OEt 4-8r 4-C1 4-CliPr S OEt OEt ..
4-OCF3 4-C1 4-CliPr S OEt OEt :
: .~
4-OCF2H 4-C1 4-CliPr S OEt OEt 3,4-CH2CtMe)2O 4-Cl4-Cl . iPr S OEt OEt -CF3 4-F 4-CliPr S OCH2C(Me)2CH2O ' -Cl 4-F 4-CliPr S OCH2C(Me)2cH2O :
4-Br 4-F 4-CliPr S OCH2C(Me)2CH2O
4-OCF3 4-F 4-CliPr S OCH2C(Me)2CH2O
` 25 4-OCF2H 4-F 4-CliPr S OCH2C(Me)2CH2O
3~4-cH2c(Me)2o 4-F 4-Cl iPr S OCH2C~Me)2CH2O
.~-CF3 2 tBu S OiPr OiPr . 4-C1 4-OCF2H 4-CltBu S OiPr OiPr 4-Br 4-OCF2H 4-CltBu S OiPr OiPr ` 30 3 2 tBu S OiPr OiPr .. 4-OCP2H 2 tBu S OiPr OiPr , .
3'4-CH2C(Me)2O 4-OCF2H 4-Cl tBu S OiPr OiPr q CF3 4-C1 4-CN tBu SOCH2cH2cH2O , 4-C1 4-C1 4-CN tBu 5CHzcH2cH2 4-Br 4-C1 4-CN tBu 2 2 2 . :
4-OCF3 . 4-C1 4-CN tBu SCH2cH2cH2 ,~
, '.
.
.
21~ ~:30~30 : ~1 R2 R3 R8 yl YlR YlR
4-OCF2H 4-C1 4-CN tBu 2 2 2 3~-c~2c(Me)2o 4-C1 4-CN tBuS CH2cH2 4-CF3 4-F 4-CN tBu 2 2 4-C1 4-F 4-CN tBu SCH2cH2 4-Br 4-F 4-CN t8u 2 2 4-OCF3 4-F 4-CN Me SOEt OEt 4-OCF2H 4-F 4-CN Me SOEt OEt 3,4-CH2C(Me)2O 4-F 4-CN Me SOEt OEt ;~ 4-Br 4-C1 4-CO2Me tBu O OEt OEt : 15 4-OCF3 4-C1 4-COzMe tBuO OEt OEt 4-OCF2H 4-C1 4-CO2Me t9u O OCH2C(Me)2CH2O
3,4-CH2C(Me)2O 4-C1 4-CO2Me tBu O OCH2C(Me)2CH2O
.
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~ble 28 5. ' , .
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; 20 ~,'!, Rl R2 R3 R8 yl R1o Y R
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; 3 4-Cl N iPr O Et OEt 4-C1 4-Cl H iPr O Et OEt 4-OCF3 4-Cl H iPr O Et OEt - . 25 4-CF3 4-F H iPr O Et O-iPr 4-OCF 4-F H iPr O Et O-iPr 4-CF3 4-OCF2H H iPr O Et O-iPr ~ 4-OCF3 4-OCF2H H iPr O Et OPh .
::. 30 3 4-Br H iPr O Et OPh t' 4-CF3 4-C1 4-Cl iPr O Ph OEt ` 4-C1 4-C1 4-Cl iPr O Ph OEt ~.~ 4-Br 4-C1 4-Cl iPr O Ph OEt ~:~
'. 4-OCF~ 4-C1 4-Cl iPr O Ph OEt :
4-CF3 4-F 4-Cl tBu O Et OEt 4-OCF3 4-F 4-CI tBu o E~ OEt .` ' ~ .
, ''':
;' ~
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,.~ . .:
Rl R2 R3 R8 yl R1o ylRll C 2 4 Cl tBu O Et O-~Pr 4-OCF3 2 Cl tBu O Et O-iPr 4-CF3 4-C1 4-~N Ph O - Et OEt 4-OCF3 4-C1 4-CN Ph O Et OEt 4-CF3 4-F 4-CN iPr S Ph O-iPr 4-OCF3 4-F 4-CN tBu S Et OEt ; .
;
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~ 20 Rl R2 R3 R9 .~ .
.. g-cF3 4-Cl H CF3 `' 3 4-F 3 , 4-OCF3 4-F H O-sec-Bu ,(~ - 25 4-CF3 4-OCF2H H 0-6ec-Bu ~, 4-Br 4-OCF2H H O-~ee-Bu 4-OCF3 4-OCF2H H O-~ec-Bu .:
4-CF3 4-Br B O-n-Bu ;
4 C 4-C1 4-Cl O-n-Bu 30 4-C1 4-C1 4-Cl O-n-Bu . :
.~ 4-Br 4-C1 4-Cl O-n-Bu . . .
~ 4-OCF3 4-C1 4-C1 O-n-Bu i 4-CF3 4-F 4-Cl O-n-heryl : 4 CF3 4-OCF2H 4-Cl O-n-he~yl 4-OCF3 4-OCF2H 4-Cl O-n-he~yl ':
. . .
, ,. '~
2~U0:1~30 Rl R2 R3 Rg j-CF 4-C1 4-CN 2 3 4-OCF3 4-C1 4_CN 2 3 4_CF3 4-C1 ~ 4-CO2Me OCH2CH20Et ', 10 .
.
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20~0130 Tablç 30 :,.
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~ -'OR10 ORl 1 ., ~ :' .
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Rl R2 R3 R10 R~
4-CF3 4-Cl H Et Et 4-CF3 4-F H Et Et 4-CF3 4-OCF2H H Et Et 4-CF3 4-Br 2 2 4-CF3 4-C1 4-Cl -CH2CH2-3D 4-C1 4-C1 4-Cl -CH2CH2-4-ocr3 4-C1 4-Cl -CH2CH2-4-CF3 4-F 4-Cl -CH2CH2CH2-4-CF3 4-OCF2U 4-C1 2CH2CH2 .
4-OCF3 4-OCF2H 4-CI -CN2C(Me)2CH2 : . . ~ ., . :: , , . . , ~ . , , . . :
.
.: : . , , 2~:~(70 ~30 ~ - R2 R3 R10 Rll 4-CF3 4-C1 4-CN -CH2C(Me)2CH2-4-OCF3 4-C1 4-CN -CH2C(Me)2CH2-4-CF3 4-F 4-CN Ph Ph 4-CF 4-Cl 4-CO2Me Ph Ph ~ .',.
; 20 ~ ~
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~ble 31 : 5 ~\
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~,' Rl R2 R3 R8 R12 ~; 4-C~ 4-Cl H nBu nBu ,~ 4-CF3 4-F H nBu nBu . 4-CF3 4-OCF2H H nBu nBu ~, - 25 4-OCF3 4-OCF2H H 2 2 2 2 2 :.
; 4-CF3 4-Br 2 2 2 2 2 -~ 4-CF3 4-C1 4-Cl -CH2CH20CH2CH2_ :;.: 4-C1 4-C1 4-Cl -CH2CH20CH2CN2_ ~ 4-OCF3 4-C1 4-Cl -CH2CH20CH2CH2_ ."~ 30 q C 3 4-F 4-Cl -CH2CH(Me)OCH(Me)CH -4-OCF3 4-F 4-Cl -CH2CH~Me)OCH(Me)CH -:, 4-CF3 4-OCF2H 4-Cl Et ~yclo-C6H
4-OCF3 2 Et c ., 4-CF3 4-C1 4-CN Et ~YCl-~6N
35 4 CF3 4-F 4-CN iPr 2 2 2 4-CF3 4-C14-CO2Me CF3 2,4-dl-Cl_Ph ... ... .
~' ' ''.
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l~ble 32 ~ N ~ R3 . . I ~
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4-CF3 4-Cl H tBu i 4-CF3 4-F H tBu !., 25 4-CF3 4-OCF2H H cec-Bu 4-OCF3 4-OCF2H H sec-Bu ~;. 4-CF3 4-Br H cec-Bu ~ 4-CF3 4-C1 4-Cl Ph '. 4-C1 4-C~ 4-Cl Ph .;
~ 4-OCF 4-C1 4-Cl Ph 4-CF3 4-F 4-C1 4-Cl-Ph 4-C1 4-F 4-C1 4-Cl-Ph ~: -s 4-OCF3 4-F 4-C1 4-Cl-Ph ~. 4-CF3 4-OCF2H 4-C1 4-Cl-Ph "` 4 OC 4-OCF2H 4-C1 2-~e-4-t-~u-Ph ~
.. , : .
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.
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Rl R2 ~3 Rlo 5 4 CF 4-C1 4-CN 2-Me-4-t-8u-Ph 4-CF3 4-C1 4-CO2Me 2-NO2-Ph ~, .: 15 .~, .
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2~013~) Formul~i~n and Use The compounds of this invention will generally be used in formulation with a carrier comprising a liquid or solid diluent or an organic solvent.
Useful formulations of thP compounds of this invention are prep~red in conventional ways. They include dusts, baits, traps, granules, pellets, solutions, suspensions, emulsions, wettable powders, emulsifiable concentrates, dry flowables and the like. Many of thes can be applied directly.
Sprayable formulations can be extended in suitable media and used at spray volumes of from about one to several hundred liters per hectare. High strength compositions are primarily used as intermediates for further formulation. The formulations, broadly, contain about 1% to 99~ solid or liquid diluent(s).
More specifically, they will contain these 20 ingredients in the following approximate proportions: -' .
Percent by Weiaht Active Inaredient Diluent(s~ ~F~actant(s~
25 Wettable Powders 25-90 0-74 0-10 Oil Suspensions, 1-50 40-95 0-35 ` Emulsions, Solutions (including Emulsifi-able Concentrates) Dusts 1-25 70-99 0-5 - 30 l!?
Granules, Baits 0.01-955-99 0-15 ~nd Pellets High Strength 90-99 0-10 0-2 Compositions Lower or higher levels of active ingredient can, of course, be present depending on the intended .
. .
-: - ~- ~ . , , . ... : ,, , . . i ; ~ -: : : ' ' 2000~30 use and the physical properties of the compound.
Higher ratios of surfactant to active ingredient are sometimes desirable, and are achieved by incorporation into the formulation or by tank mixing.
Typical solid diluents are described in Watkins, et al., "Handbook of Insecticide Dust Diluents and Carriers," 2nd Ed., Dorland Books, Caldwell, New Jersey. The more absorptive diluents are preferred for wettable powders and the denser ones for dusts. Typical liquid diluents and solvents are described in Marsden, ~Solvents Guide,~ 2nd Ed., ; Interscience, New York, 1950. Solubility under 0.1%
is preferred for suspension concentrates; solution concentrates are preferably ~table against phase separation at 0C. "~cCurcheon's Detergents and Emulsifiers Annual," Allured Publ. Corp., Ridgewood, New Jersey, as well as Sisely and Wood, "Encyclopedia of Surface Active Agents," Chemical Publ. Co., Inc., New York, 1964, list surfactants and recommended uses.
All formulations can contain minor amounts of addi-tives to reduce foam, caking, corrosion, microbiologi-cal growth, etc. Preferably, ingredients should be approved by the U.S. Environmental Protection Agency for the use intended.
The methods of making such compositions are well known. Solutions are prepared by simply mixing the ingredients. Fine solid compositions are made by blending and, usually, griding as in a hammer or fluid energy mill. Suspensions are prepared by wet-milling (see, for example, U.S. 3,060,084). Granules and pellets can be made by spraying the active material upon preformed granular carriers or by agglomeration techniques. See Browning, "Aqglomeration,~ Chemical , . ' :
- ' -~ ' , . ' .''' .. :...... : ' ~, 19~ -Enaineerinq, December 4, 1967, pages 147 and follow-ing, and ~Perry's Chemical Engineer's Handbook,~ 4th Ea., McGraw-Hill, New York, 1963, pages 8 to 59 and ollowing.
Many of the compounds of the invention are most efficacious when applied in the form of an emul-sifiable concentrate mi~ed with a spray oil or spray oil concentrate. Although any oil can be used as a spray oil, spray oils usually have these character-istics: they are not phytotoxic to the crop sprayed, and they have appropriate viscosity. Petroleum based oils are commonly used for spraying. In some areas, crop oils are preferred such as the following:
~ommon Crop_Oils Us~d as SP~Y Oils Corn Oil Linseed Oil Cottonseed Oil Soybean Oil ` 20 Coconut Oil Sunflower Oil Rapeseed Oil Olive Oil Peanut Oil Palm Oil ~afflower Oil Sesame Oil ~ ;
Mustardseed Oil Castor Oil The following oils also meet the criteria for a spray oil: mineral, fish and cod liver oil.
Spray oil concentrates comprise a spray oil together with one or more additional ingredients such as emulsifiers and wetting agents. A number of useful spray oil and spray oil concentrates can be found in ~A Guide to Agricultural Spray Adjuvants Used in the United States" by Thomson, Thomson Publications, California, 1986.
E~amples of useful arthropodicidal formulations of compounds of the present invention are as follows.
` -, .
. .- .
20(~0~30 Example A
Emulsifiable Concentrate 5 methyl 4-[3-(4-chlorophenyl)-1-[[(ethoxycarbonyl)(l- ;
methylethyl)amino]thio]-N-t4-(trifluoromethyl)phenyl]-amino]carbonyl]-~,5-di-hydro-lH-pyrazo1-4-yl]benzoate.
20%
blend of oil soluble sulfonates and lo polyoxyethylene ethers 10%
isophorone 70%
The ingredients are combined and stirred with gentle warming to speed solution. A fine screen -filter is included in packaging operation to insure the substantial absence of extraneous undissolved ; material in the product.
.~ .
Example B
Wetta~l~ Po~ E
methyl 4-[3-(4-chlorophenyl)-1-[~(ethosycarbonyl)(l-. methylethyl)amino]thio]-N-[4-(trifluoromethyl)phenyl]-amino]carbonyl]-4,5-di-hydro-lH-pyrazol-4-yl]benzoate.
30%
- 25 sodium alkylnaphthalenesulfonate2%
sodium ligninsulfonate 2%
. synthetic amorphous silica 3%
kaolinite 63%
The active ingredient is mixed with the inert materials in a blender. After grindin~ in a hammer-mill, the material is reblended and sifted throu~h a ` 5-mesh screen.
. ~.
E~ample C
nu~
methyl 4-t3-~4-chloroPhenYl)-l-[[(ethoxYcarbonyl)(l-methylethyl)amino]thio]-N-t4-~trifluoromethyl)phenyl]-amino~carbonyl]-4,5-di-hydro-lH-pyrazol-4-yl]benzoate.
., ~ .
,, , : ~ ~ , ;...... ~ . .
. . - .
20(~0130 Wettable powder of Example B 10%
pyrophyllite (powder~ 90%
The wettable powder and the pyrophyllite diluent are thoroughly blended and then packeged.
The product is suitable for use as a dust.
Example D
Granule ` methyl 4-[3-(4-chlorophenyl)-1-[[(etho~ycarbonyl)-(l-methylethyl~amino]thio]-N-[4-(trifluoro-methyl)phenyl]amino]carbonyl]-4,5-di-hydro-lH-pyrazol-4-yl]benzoate. 10%
attapulgite granules (low volative matter, 0.71/9/30 mm; U.S.S. No.
25-50 sie~es) 90%
The active ingredient is dissolved in a vola-tile solvent such as acetone and sprayed upon dedusted and pre-warmed attapulgite granules in a double cone blender. The acetone is then driven off by heating.
The granules are then allowed to cool and are packaged.
E~ample E
~,~
` 25 Emulsifiable Concentrate ..
methyl 4-[3-(4-chlorophenyl)-1-[[(ethoxycarb~nyl)~l-methylethyl)amino]thio]-N-[4-(trifluoromethyl)phenyl]-amino]carbonyl]-4,5-di-hydro-lH-pyrazol-4-yl]benzoate.
^ 10%
blend of oil soluble sulfonates and polyo~yethylene ethers 4%
isophorone 86%
The ingredients are combined and stirred with gentle warming to speed solution. A fine screen filter is included in packaging operation to insure the ab-sence of any e~traneous undissolved material in the ~
product. ~i .~ . .
' ' .
, : :
-Z13()0130 Example F
Wettable P~wder s methyl 4-[3-(4-chlorophenyl)-1-[l(etho~ycarbonyl)(l-methylethyl)amino]thio]-N-[4-(trifluoromethyl)phenyl]-amino]carbonyl]-4,5-di-hydro-lH-pyrazol-4-yl]benzoate 80%
sodium alkylnaphthalenesulfonate 2%
sodium ligninsulfonate 2%
synthetic amorphous silica 3%
kaolinite 3%
- The active ingredient is blended with the inert materials in a blender. After grinding in a hammermill, the material is reblended an sifted through a U.S.S. 50-mesh screen and packaged.
.~ .
E~ample G
"`~ E~ '' wettable powder of E~ample F 5%
. , .
pyrophyllite (powder) 95%
The wettable powder and the pyrophyllite ; diluent are thoroughly blended and then packaged.
The product is suitable for use as a dust.
Example H
Granule methyl 4-[3-(4-chlorophenyl)-1-[[(ethoxycarbonyl)(l-' methylethyl)amino~thio]-N-[4-(trifluoromethyl)phenyl]-amino]carbonyl]-4,5-di-hydro-lH-pyrazol-4-yllbenzoate.
,` 1~%
attapulgite granules (low volative matter, 0.71/0.30 mm; U.S.S. No. 25-S0 sieves) 90%
The active ingredient is dissolved in a suit-able solvent and sprayed onto dedusted attapulgite granules in a double cone blender. The granules are - warmed to drive off solvent, cooled and packaged.
, , .,,, ; .
2~(~013~
Example I
Granule wettable powder of E~ample F 15%
gypsum 69% !
potassium æulfate 16%
The ingredients are blended in a rotating mixer and water is sprayed on to accomplish granu-lation. When most of the material has reached the desired range of 0.1 to 0.42 mm (U.S.S. No. 18 to 40 sieves), the granules are removed, dried, and screened. Oversize material is crushed to produce additional material in the desired range. These qranules contain 12% active ingredient.
.'. :
~xample J
Solu~ion methyl 4-[3-(4-chlorophenyl)-1-[[(ethoxycarbonyl~
methylethyl)amino]thio]-N-[4-(trifluoromethyl)phenyl]-amino]carbonyl~-4,5-di-hydro-lH-pyrazol-4-yl]benzoate.
'~` 15%
4-butyrolactone 85%
-~ The ingredients are combined and stirred to produce a solution suitable for direct, low volume application.
-~ Examp~e K
Oil Suspension methyl 4-t3-(4-chlorophenyl)-1-[t(etho~ycarbonyl)(l-methylethyl)amino]thio]-N-t4-(trifluoromethyl)phenyl]-amino]carbonyl]-4,5-di~hydro-lH-pyrazol-4-yl]benzoate.
r 2 0 %
sodium alkylnaphthalenesulfonate 4%
sodium ligninsulfonate 4%
low viscosity methyl cellulose 3~ -~
attapulgite 69%
... .
,',, ' :' , ,. . .
. .
Z~OO~L30 The active ingredient is blended with the inert materials in a blender. After grinding in a hàmmermill to produce particles substantially all below 100 microns, the material is reblended and sifted through a U.S.S. 50-mesh screen and packaged.
Example L
10 Aqueous Susp~nsi~n -methyl 4-[3-(4-chlorophenyl)-1-[[(ethoxycarbonyl)-(l-methylethyl)amino~thio]-N-[4-(trifluoromethyl)-phenyl]amino]carbonyl]-4,5-dihydro-lH-pyrazol-4-yl]benzoate. 40%
polyacrylic acid thickener 0.3%
dodecyclophenol polyethylene glycol ether 0.5%
disodium phosphate 1.0%
monosodium phosphate 0.5%
polyvinyl alcohol i.o%
water 56.7 ~; The ingredients are blended and ground together in a sand mill to produce particles substantially all under 5 microns in size.
Ezample M
Oil ~uspensi~on methyl 4-t3-(4-chlorophenyl)-1-[[(ethoxycarbonyl)-; (l-methylethyl)amino]thio]-N-[4-(trifluoromethyl)-phenyl~amino~carbonyl]-4,5-dihydro-lH-pyrazol-4-yl]benzoate. 35-0%
blend of polyalcohol carbo~ylic 6.0%
esters and oil soluble petroleum sulfonates xylene range solvent 59.0%
- .
.' ' ,:
': . .-2~00~30 The ingredients are combined and ground tegether in a sand mill to produce particles substantially all below 5 microns. The product can be used directly, e~tended with oils, or emulsified in water.
Example Emulsifiabl,e Concentrate methyl 7-chloro-2-[[N-[[[(hexylo~y)carbonyl]-methyl-amino]-thio]-N~[4-(trifluoromethyl)-phenyl]amino]-; carbonyl]-3,3a,4,5-tetrahydro-2H-benz[g]indazole-3a-., carboxylate. 5%
blend of oil soluble sulfonates , ' and polyoxyethylene ethers 4%
xylene 91%
,' The ingredients are combined and stirred with gentle warming to speed solution. A fine screen 20 filter is includ,ed in packaging operation to insure ;~
the absence of any extraneous undissolved material in ,:
the product.
~, Example O
~, 25 ~ettable Powder methyl 7-chloro-2-[[N-[[[(he~yloxy)carbonyl]-methyl- ''-' amino]-thio]-N-[4-(trifluoromethyl)-phenyl]amino]- - carbonyl]-3,3a,4,5-tetrahydro-2H-benz[g~indazole-3a-" carboxylate. 30%
- 30 sodium alkylnaphthalenesulfonate2%
, sodium ligninsulfonate 2%
synthetic amorphous silica 3%
, kaolinite 63% ', .
' . . .
,; .
2~)00130 .
The active ingredient, warmed to reduce viscosity, is sprayed onto the inert materials in a blender. After grinding in a hammer-mill, the material is reblended and sifted through a 50 mesh screen.
E~ample P
Solution methyl 7-chloro-2-[[N-[[[(he~yloxy)carbonyl]-methyl-amino]-thio]-N-[4-(trifluoromethyl)-phenyl]amino]-carbonyl]-3,3a,4,5-tetrahydro-2H-benz[g]indazole-3a-carboxylate. 10%isophorone 90%
- The ingredients are combined and stirred to -produce a solution suitable for direct, low volume application.
E~m~le O
Bait Granul~s methyl 4-[3-(4-chlorophenyl)-1-tt(ethoxycarbonyl)-(l-methylethyl)amino]thio]-N-[4-(trifluoromethyl)-phenyl]amino]carbonyl]-4,5-dihydro-lH-pyrazol-4-yl]benzoate. 3.0%
blend of polyethoxylated nonyl-9.0%
phenols an sodium dodecylbenzene r'~' benzene sulfonates ground up corn cobs 88.0%
The active ingredient and surfactant blend are dissolved in a suitable solvent such as acetone and sprayed onto the ground corn cobs. The granules are then dried and packaged. Compounds of Formula I, II and/or III can also be mi~ed with one or more oth2r insecticides, fungicides, nematocides, bactericides, acaricides, or other biologically active compounds to .-:
20(~0130 form a multi-component pesticide giving an even broader spectrum of effective pesticide protection.
Esamples of other agricultural protectants with which compounds of the present invention can be mixed or formulated are as follows.
Insecticides:
3-hydrosy-N-methylcrotonamide(dimethylphosphate)ester (monocrotophos) methylcarbamic acid, ester with 2,3-dihydro-2,2-: 15 dimethyl-7-benzofuranol (carbofuran) ; 0-[2,4,5-trichloro-a-(chloromethyl~benzyl]ophosphoric acid, 0',0'-dimethyl ester (tetrachlorvinphos) .
2-mercaptosuccinic acid, diethyl ester, S-ester with thionophosphoric acid, dimethyl ester (malathion3 phosphorothioic acid, 0,0-dimethyl, 0-D-nitrophenyl ester ~methyl parathion) methylcarbamic acid, ester with a-naphthol (carbaryl) -methyl 0-(methylcarbamoyl)thiolacetohydrosamate ; (methomyl) -25 N'-(4-chloro-Q-tolyl)-N,N-dimethylformamidine (chlordimeform) . ..
0,0-diethyl-0-(2-isopropyl-4-methyl-6-pyrimidylphos- ;
phorothioate (diazinon) .
`. octachlorocamphene (tosaphene) 30 0-ethyl 0-p-nitrophenyl phenylphosphonothioate (EPN~ , (S)-a-cyano-m-phenosybenzyl(lR,3R)-3-(2,2-dibromovinyl) -2,2-dimethylcyclopropanecarbosylate (deltamethrin) Methyl :
N',~'-dimethyl-N-t(methylcarbamoyl)oxy]-l-thioosamimi-date (osamyl) cyano(3-phenosyphenyl)-methyl-4-chloro-a-(1-methyl-ehtyl)benzeneacetate ~fenvalerate) ~-.
. ., ~ . . , -' ' ' . ': , :' '' 2;1~(30130 2~7 (3-pheno~yphenyl)methyl(~)-c s,trans-3-(2,2-dichloro .5 ethenyl)-2,2-dimethylcyclopropanecarbo~ylate (perme-thrin) a-cyano-3-pheno~ybenzyl 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carbosylate (cypermethrin) O-ethyl-S-(~-chlorophenyl)ethylphosphonodithioate lQ (profenofos) phosphorothiolothionic acid, :O-ethyl-0-[4-(methylthio)-phenyl]-S-n-propyl ester (sulprofos).
Additional insecticides are listed hereafter by their common names: triflumuron, diflubenzureon, methoprene, buprofezin, thiodicarb, acephate, azinphos-methyl, chlorpyrifos, dimethoate, fonophos, isofenphos, methidathio, methamidiphos, monocrotphos, phosmet, phosphamidon, phosalone, pirimicarb, phorate, profenofos, terbufos, trichlorfon, metho~ychlor, :~ bifenthrin, biphenate, cyfluthrin, fenpropathrin, ~ fluvalinate, flucythrinate, tralomethrin, metal- .
: dehyde and rotenone.
:
. methyl 2-benzimidazolecarbamate (carbendazim) -tetramethylthiuram disulfide (thiuram) : n-dodecylguanidine acetate (dodine) manganese ethylenebisdithiocarbamate (maneb) 1,4-dichloro-2,5-dimetho~ybenzene (chloroneb) methyl l-(butylcarbamoly)-2-benzimidazolecarbamate : (benomyl) .~, .
:, . . . ..
2V~ 30 1-[2-(2,4-dichlorophenyl)-4-propyl-1,3-dio~olan-2-ylmethyl3-lH-1,2,4-triazole (propiconazole) ~:
2-cyano-N-ethylcarbamoy-2-methoxyiminoacetamide (cymoxanil) 1-(4-chlorophenoxy)-3,3-dimethyl-1-(lH-1,2,4-triazol-1-yl)-2-butanone (triadimefon) N-(trichloromethylthio)tetrahydrophthalimide (captan) N-(trichloromethylthio)phthalimide (folpet) l-[[[bis(4-fluorophenyl)][methyl]silyl]methyl]-lH- .
1,2,4-triazole.
NematQcide~:
: 15 S-methyl l-(dimethylcarbamoyl)-N-(methylcarbamoyloxy)-thioformimidate : S-methyl ~ l-carbamoyl-N-(methylcarbamoyloxy)thioformimidate ` N-isopropylphosphoramidic acid, O-ethyl 0~-[4-(methylthio)-m-tolyl]diester (fenamiphos) Bac.~ericid~
tribasic copper sulfate streptomycin sulfate , .: 25 acariciaes:
senecioic acid, ester with 2-~Q~-butyl-4,6-dinitro-phenol (binapacryl) 6-methyl-1,3-cithiolo[4,5-B]quino~alin-2-one (oxythioquinox) ethyl 4,4'-dichlorobenzilate (chlorobenzilate) 1,1-bis(~-chlorophenyl)-2,2,2-trichloroethanol ; (dicofol) :
bis(pentachloro-2,4-cyclopentadien-1-yl) (dienochlor) tricyclohexyltin hydroxide (cyhexatin) :~ trans-5-(4-chlorophenyl)-N-cyclohexyl-4-methyl-2-oxo- ;
thiazolidine-3-carboxamide (hexythiazox) .
.. .. ~ . ... . . ..
.: . :.
.
Z~)0~:130 amitraz propargite fenbutatin-o~ide ~iologi~1 ~acillus thuringiensis Avermectin ~.
Utilitv The compounds of the present invention ex-hibit activity against a wide spectrum of foliar and soil-inhabiting, livestock, household and public health arthropods. Those skilled in the art will recognize that not all compounds will be equally ; effective against all arthropods but the compounds of : this invention display activity against economical-; ly important pest species, such as grasshoppers and 20 cockroaches including German or American roaches; ;
thrips; hemipterans: plant bugs (Miridae) such as tarnished plant bugs, lace bugs (Tingidae), seed bugs (Lygaeidae) such as cinch bugs, stink bugs (Pentatomidae), leaf-footed bugs (Coreidae) such as squash bug, and red bugs and stainers ~Pyrrocoridae) such as cotton stainer; also homopterans such as .~ whiteflies, aphids such as the green peach aphid, greenbug and cotton aphid, leafhoppers, spittlebugs . and planthoppers such as aster leafhopper, potato :~ 30 leafhopper and rice planthoppers, psyllids such as pear psylla, scales (coccids and diaspidids) and mealybugs; coleopterans including weevils such as boll weevil and rice water weevil, grain borers, chrysomellid beetles such as Colorado potato ~eetle, .
3S flea beetles and other leaf beetles, coccinellid beetles su~h ~s Me~ican bean beetle.
.
- . ., : ............... - .. . :: .. . - . . , ...... . ~ . .
, . . .. . ;:.~ .~ , . , -, , ., ,~ : - , , - . . -- . . . : . . ,. . .- . - : : -,. : ,. - . : . . : . :: . : - :
2V()0130 Activity is also shown against soil insects such as southern corn rootworm and wireworm;
lepidopterous larvae including noctuids such as fall armyworm, beet armyworm, other Spodoptera spp., Heliothis spp. such as virescens, Heliothis zea, cabbage looper, green cloverworm, velvetbean ; caterpillar, cotton leafworm, black cut- worm, and other noctuid cutworms and including pyralids such as . European corn borer, navel orange- worm, and :.
: stalk/stem borers and including tortricids like codling moth and grape berry moth as well as other .
lepidopterous larvae such as pink bollworm and diamodback moth; and dipterans such as leaf-miner, soil maggots, midges, and tephritid fruit . flies; house fly, Musca domestica; stable fly, Stomoxys calcitra.n~; black blow fly, Phormi-~ regin~;
face fly, ~u.sca autumn~l.is; black fly, Simulum 20 meri~ionale; yellow fever mosquito, Aedes eqypti; :.:
; German cockroach, Blattella aermanica; carpenter ants, :~ CamponQ~us pennsylvanicus and eastern subterranean ..
: termite, Reticulitermes flavipes. The pest control ` afforded by the compounds of the present invention is . 25 not limited, however, to these species.
The specific species, for which control is ~ esemplified below, are: fall armyworm, Spodoptera frugiperda; tobacco budworm, Heliothis virescens;
southern corn rootworm, Diabrotica undecimpunctata 3u howardi; aster leafhopper, Macrosteles fascifrons.
The pest control afforded by the compounds of the present invention is not limited, however, to these species.
Appliss~i9L
Arthropods are controlled in agricultural crops and animals and humans are protected by applying one or more of the compounds of this invention, in an ~, . .
Z~)~)013V
effective amount, to the locus of infestation, to the S area to be protected, directly to the pests to be controlled, or to their environment. A preferred method of application is by spraying with spray equipment that distributes the compound on the foliage, in the soil, or to the plant part that is infested or needs to be protected. AlternatiYely, granular formulations of these compounds can be applied to soil or foliage or, optionally, incorporated into the soil. Either aerial or ground i application can be used. Because of the diversity of behavior patterns and habitats of the animal and human health species, many different methods of application are employed. These include direct and residual - sprays, baits, ear tags, soil treatment and many others.
The pyrazoline compound(s) of this invention can be applied directly, but most often application will be of a formulation comprising one or more com-pounds of this invention, in an agriculturally suit-able carrier or diluent. A most preferred method of - 25 application involves spraying a water dispersion or refined oil solution of the compounds. The compound(s) can also be incorporated into baits which are consumed or in devices such as traps and the like that entice the arthropod to ingest or otherwise contact the to~icant compound(s).
The rate of application of Formula I, II or III compounds reguired for effective control will depend on such factors as the species of arthropod to be controlled, the pest's life stage, its 3ize, its location, the host crop, time of year of application, ambient moisture, temperature conditions, and the like. In general, application rates of 0.01 to 2 kg of active ingredient per hectare are sufficient ", '.
.
. . ' :, . ;.,~ - ,., , . , ~ . . . ~ , . : .. . . , . , , .... - .
:~ 2~00~30 . .
to provide effective control in large scale field operations under normal circumstances, but as little as 0.001 kg/hectare may be sufficient or as much as 8 kg/hectare may be required for agricultural use, or 0.1 mg/ft2 to 20 mg/ft2 for home use, depending upon the fact~rs listed above.
The following Examples demonstrate the con-trol efficacy of compounds of Formulae I, II and III
on specific arthropod pests wherein Compounds 1 through 55 are depicted in the Examples and Tables A, B and C and summarized in Table D, respectively.
, ~
- .
~ 20 ''- .
, , .
. 25 .
.
'~
.' ' .
:' ' ., : ' ' ' ' . ' , : :
- : . : -- . , : - , .
: - . ' .' ,' ' ' '' ~ ~
Table D
.
.. ' R2 ~ O2CH3 N-N
C-N ~ R~
o sY .:
-:
:
: CMPD Rl R2 Y
: 1 CF3 H N(CHtCH3]2)Co2Et ~ -. 2 CF3 H CO2~-Bu 3 CF3 H N(n-Bu)2 4 CF3 5-Cl N(CH3)CO2n-hexyl ~ 5 CF3 ~ N(CH3)cO2n-Bu : 6 CF3 H N(CH3)C2Et i;~ 7 CF3 4-F N(CH3)CO2n-~U
,. 8 CF3 - H N(CH3)CO2cyclohexyl 9 CF3 H N(cH3)co2n-octyl "r 30 10 CF3 H N(CH3)CO2n-decyl ~:.
'j 11 CF3 4-F N[CH(CH3)2]CO2Et . 12 CF3 H N(CH3)CO2n-dodecyl - 13 CF3 H N(CH3)CO2n-hexyl : 14 CF3 5-Cl CO2~-Bu CF3 5-Cl N[cH(cH3)2]co2Et 16 CF3 5-Cl N(CH3)CO2Et . . .
,: , .'', ''" .
"~ .
:.
' ' - ! r ' , .
.
, , - CMPD Rl R2 Y
. , _ . .
17 CF3 5-Cl N(CH3)C02n~octyl 18 CF3 4-F C02S-Bu : 19 CF3 5-Cl ~(CH3)C02n-Bu CF3 5-Cl N[CH3(CH3)2]C02n-BU
: 10 21 CF3 5-Cl N(cH3)co2n-dode 22 CF3 5-Cl N(cH3)co2cyclohe~yl 23 CF3 5-Cl N(CH3)C02(CH2)208U -:
24 CF3 5-Cl N(CH3)C02cl4H29 CF3 5-Cl N(CH3)C02c16H33 26 CF3 5-Cl N(CH3)C02c18H37 27 CF3 5-Cl N(CH3)C02c22H45 28 CF3 5-Cl N(cH3)co2(cH2)2o(cH2)2oBu .
.
:~ 20 :~ N ~
~`. 25 . -;
~s C--N~3R, ,., O SY , " , .'`'. '' :' ' - ', : .
.. . :
., , - . . . , . . , - . . . - , ,. . ; .. : . : : :
i ,' ' ' , " ". "', '' ': " ' ' ' ", ' ` ' ' :..... " ' ~ '' ~ .
.: . . .- : - . , ,-' , :,' ' , . ' :' ,' ' ,. . ;
- . . . ..
2~1Ul30 5 CMPD Rl R2 R3 Y
. . . _ 29 CF3 4-C1 4-F N[CH(CH3)2]C02Et .:
31 CF3 4-C1 4-F N[CH(CH3)2]CO2BU
32 CF3 4-C1 4-F N[cH(cH3)cH2cH3]co2Et 33 CF3 4-Cl 4-F C02~-Bu 10 34 CF3 4-C1 4-F N(CH3)CO2cyclohexyl .
:- .
~ [~R3 R2 /~
,,. N~N/
20 O'C~N~R, .. .' ' .
~'. 25 :
.... .
. CMPD Rl R2 R3 Q
CF3 4-C1 4-Cl SN[CH(CH3)2]COZEt CF3 4-C1 4-Cl SN(CH3)CO2s-Bu ;i 3036 CF3 4-C1 4-Cl SCOz~-Bu ~-~' 37 Cl 4-C1 4-Cl SCO2~-Bu ~: 38 CF3 4-C1 4-Cl CO2CH3 CF3 4-C1 4-Cl SN[cH(cH3)z]co2Et 9 3541 CF3 4-C1 4-Cl COCH3 . 42 4-C1 4-C1 4-F COCH3 ::
93 Br 4-C1 4-F COCH3 . ' , " ~
.
-2~00iL~ ~
CMPD Rl R2 R3 Q
CF3 4-C1 4-F COPh 46 CF3 4-C1 4-Cl COCH2CH3 47 CF3 4-C1 4-Cl COCOCH2CH3 : 48 CF3 4-C1 4-Cl COn-Bu 49 Cl 4-C1 4-Cl COCH3 ` 50 Cl 4-C1 4-Cl COCH2CH3 ; 51 Cl 4-C1 4-Cl CO2CH3 . 15 52 CF3 4-C1 4-Cl CO-4-Cl-Ph .` 53 CF3 4-C1 4-Cl COt-Bu 54 CF3 4-C1 4-Cl CO2Ph ~`.~ ;.
,.
~ 20 ,..
.,',. .
~` :
:~25 ., .
.`~' ~', ~`- ,';
~ -' , ' .
.. ` ~
~:
~ ;'' ~, . ~
2~ 30 E~ample 56 Fall Armyworm S Test units, each consisting of an 8-ounce plastic cup containing a layer vf wheat germ diet, approx. 0.5 cm thick, were prepared. Ten third-instar larvae of fall armyworm (Spodoptera frugiperda~ were placed into each cup. Solutions of each of the test compounds (acetone/distilled water 75/25 solvent) were sprayed onto the cups, a single solution per set of three cups. Spraying was accomplished by passing the cups, on a conveyor belt, directly beneath a flat fan hydraulic nozzle which discharged the spray at a rate of O.S pounds of ~-~ active ingredient per acre (about 0.55 kg/ha) at 30 p.s.i. The cups were then covered and held at 27C
and 50% relative humidity for 72 hours, after which time mortality readings were taken.
Of the compounds tested on fall armyworm, the following resulted in greater than or equal to 80 mortality: 1, 2, 9, 5, 6, 7, 9, 10, 11, 12, 13, 16, 17, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 35, 36, 38, 41, 92, q3, 44, 45, 46, 47, 25 48, 49, 50, 51, 52, 53, and 54.
., .'~
Tobacco ~udworm The test procedure of Esample 56 was repeated for efficacy against third-instar larvae of the tobacco budworm (Heliothis virescens) e~cept that mortality was assessed at 98 hours. Of the compounds tested on tobacco budworm, the following resulted in greater than or equal to 80% mortality: 2, 4, 7, 11, 35 16, 17, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29;
30, 31, 32, 33, 35, 36, 38, 41, 42, ~3, 44, 45, 46, 48, 49, 50, 51, 52, 53 and 54.
., , , :
.
~-: ;
: ' ' ' '.' .: ', ~ ' ' : ' ' ' `, ' ' ~ , '' , ~ ' . .' . , . " ~, ,,':
20(:~0:~3~) ~ampkQ_~
European Corn Borer Test units, each consisting of an 8-ounce - plastic cup containing a one-inch square of wheat germ/soyflour diet, were prepared. Five third-instar larvae of the European corn borer (Ostrinia nubilalis) were placed into each cup. Sets of three test units were sprayed as described in Example 56 with indi-vidual solutions of the test compounds. The cups were then covered and held at 27C and 50% relative humidity for 48 hours, after which time mortality readings were taken. Of the compounds tested on European corn borer, the following resulted in greater than or e~ual to 80% mortality: no testing.
E~ample 59 Southern Corn Rootworm Test units, each consisting of an 8-ounce plastic containing 1 sprouted corn (Zea mays) see, were prepared. Sets of three test units were sprayed as described in Example 56 with individual solutions of the test compounds. After the spray on the cups had dried, five third-instar larvae of the southern corn rootworm (Diabrotica undecimpunctata howardi) - were placed into each cup. A moistened dental wick was inæerted into each sup to prevent drying and the cups were then covered. The cups were then held at 27C and 50% relative humidity for 48 hours, after which time mortality readings were taken.
Of the compounds tested on southern corn rootworm, the following resulted in greater than or 35 equal to 80% mortality: 1, 2, 3, 4, 6, i, 9, 10, 11, 13, 16, 17, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, ^ 29, 30, 31, 32, 35, 36, 38, 41, Ç2, 44, 45, 47, 48, 49 and 51.
.
:,~
:- , , . -. . .. . : :,. . .
;~ , :
. .
E~ample ~0 Aster Leafhopper Test units were prepared from a series of 12-ounce cups, each containing oat (Avena ~ativa) seedlîngs in a l-inch layer of sterilized soil. Sets of three test units were sprayed as described in Example 56 with individual solutions of the below-listed compounds. After the oats had dried from the spraying, between 10 and 15 adult aster leafhoppers ; (Mascrosteles fascifroms) were aspirated into each of 15 the cups. The cups were held at 27C and 50% relative ~
humidity for 48 hours, after which time mortality -readings were taken.
Of the compounds tested on aster leafhopper, the following resulted in greater than or equal to 80% !~
20 mortality: 1, 2, 3, 9, 6, 7, 8, 9, 10, 11, 12, 13, ` 16, 17, 19, 20, 21, 22, 23, 24, 25, 26, 28, 30, 31, 35, 36, 38, 41, 42, 43, 44, 45, 47, 49, 50 and 51.
: .
Ex~mDle 61 Boll Weevil - Five adult boll weevils (Anthonomus grandis) were placed into each of a series of 9-ounce cups.
The test procedure employed was then otherwise the same as in Esample 56 with three cups per treatment.
Mortality readings were taken 48 hour~ after treatment.
` Of the compounds tested on boll weevil, the following resulted in greater than or equal to 80%
mortality: 16, 21, 22, 23, 24, 25, 26, 27, 28, 30, 35, 36, 38, 41, 42, 43, 44, 46, 48, 49, 50, 51, 52 and 54.
. , .
: : . :
,. . . .: . . . . : ~, :. .. .. .... .. ~ - . :
Claims (8)
1. A compound of the formula:
I II
III
wherein A is a 1, 2 or 3-atom bridge comprising 0 to 3 carbon atoms, 0 to 1 oxygen atoms, NR6, or S(O)q, wherein each carbon individually can be substituted with 1 to 2 substituents selected from 1 to 2 halogen, C1 to C6 alkyl, C2 to C4 alkoxycarbonyl or phenyl optionally substituted with 1 to 3 substituents independently selected from W and one of the carbon atoms can be combined into the group C(O) or C(S);
B is H, C1 to C6 alkyl, C4 to C7 cycloalkyl alkyl, C3 to C6 cycloalkyl optionally substituted with 1 to 2 halogens or 1 to 2 CH3; C1 to C6 haloalkyl, C2 to C6 alkenyl, C2 to C6 haloalkenyl, C2 to C6 alkynyl, OR7, C2 to C6 alkoxyalkyl, C2 to C6 cyanoalkyl, C3 to C8 alkoxycarbonylalkyl, CO2R4, C(O)R4, C(O)NR4R5, C(S)NR4R5, C(S)R4, C(S)SR4, phenyl, phenyl substituted by (R14)p, benzyl, or benzyl substituted with 1 to 3 substituents independently selected from W;
J is H, C1 to C4 alkyl or phenyl optionally substituted with W;
K is H or CH3;
q is 0, 1 or 2;
R1, R2, and R14 are independently selected from R4, halogen, CN, N3, SCN, NO2, OR4, SR4, S(O)R4, S(O)2R4, OC(O)R4, OS(O)2R4, CO2R4, C(O)R4, C(O)NR4R5, S(O)2NR4R5, NR4R5, NR5C(O)R4, OC(O)NHR4, NR5C(O)NHR4 and NR5S(O)2R4; or when m, n or p is 2, R1, R2, or R14 can independently be taken together as OCH2O, OCH2CH2O or CH2CH2O, to form a 5 or 6-membered ring, each of which can be independently substituted with 1 to 4 halogen atoms or 1 to 2 methyl groups;
R4 is selected from H, C1 to C6 alkyl, C3 to C6 cycloalkyl, C3 to C8 alkoxycarbonylalkyl, C3 to C6 alkenyl, C3 to C6 alkynyl, C1 to C6 haloalkyl, C3 to C6 haloalkenyl, C1 to C6 alkyl substituted with CN, CO2CH3, CO2CH2CH3, OCH3, OCH2CH3, SCH3, SCH2CH3 or NO2, or R4 is phenyl or benzyl, either optionally substituted with W; or R4 and R5 can be taken together as (CH2)4, (CH2)5 or CH2CH2OCH2CH2;
R5 is selected from H, C1 to C4 alkyl, C3 to C4 alkenyl, C3 to C4 alkynyl or C1 to C4 halo-alkyl;
m, n and p are independently 1 to 3;
W is halogen, CN, NO2, C1 to C2 alkyl, C1 to C2 haloalkyl, C1 to C2 alkoxy, C1 to C2 halo-alkoxy, C1 to C2 alkylthio, C1 to C2 halo-alkylthio, C1 to C2 alkylsulfonyl or C1 to C2 haloalkylsulfonyl;
R6 is H, C1 to C4 alkyl, C1 to C4 haloalkyl, C2 to C4 alkenyl, C2 to C4 haloalkenyl, phenyl optionally substituted with W or benzyl optionally substituted with W;
R7 is H, C1 to C4 alkyl, C2 to C4 alkenyl, C2 to C4 alkynyl, C2 to C4 alkylcarbonyl, C2 to C4 alkoxycarbonyl or C1-C4 alkylsulfonyl;
Q, Y and Z are independently selected from SX;
X is NR8?R9, NR8S(O)aR9, NR8R12 or SR10 R8 and R12 are independently C1 to C6 alkyl, C1 to C6 haloalkyl, C3 to C6 cycloalkyl, C4 to C7 cycloalkylalkyl, phenyl optionally substituted by 1 to 2 substituents selected from W, benzyl optionally substituted by 1 to 2 substituents independently selected from W, phenethyl optionally substituted by 1 to 2 substituents independently selected from W, C2 to C6 cyanoalkyl, C2 to C6 alkoxyalkyl, C3 to C8 alkoxycarbonylalkyl, C4 to C8 dialkylaminocarbonylalkyl; or R8 and R12 can be taken together as (CH2)4, (CH2)5 or (CH2)2O(CH2)2, R9 is F, C1 to C22 alkyl, C3 to C6 cycloalkyl, C3 to C6 cycloalkoxy, C2 to C8 dialkylamino, C1 to C6 haloalkyl, phenyl or phenoxy either optionally substituted by 1 to 2 substituents independently selected from W; C1 to C22 alkoxy, C1 to C4 alkoxy substituted by cyano, nitro, C2 to C4 alkoxy, C4 to C8 alkoxyalkoxy, C1 to C2 alkylthio, C2 to C3 alkoxycarbonyl, C3 to C5 dialkylaminocarbonyl, phenyl or 1 to 6 halogens; or R9 is morpholino, piperidino or pyrrolidino, 1-naphthoxy, 2,2-dimethyl-2,3-dihydrobenzofuranoxy-7 or ON=C(CH3)SCH3;
R10 and R11 are independently C1 to C4 alkyl, C2 to C4 haloalkyl or phenyl optionally substituted by 1 to 2 substituents independently selected from W; or R10 and R
can be taken together as (CH2)2, (CH2)3 or CH2C(CH3)2CH2;
Y' is S or O; and a is 0 to 2.
I II
III
wherein A is a 1, 2 or 3-atom bridge comprising 0 to 3 carbon atoms, 0 to 1 oxygen atoms, NR6, or S(O)q, wherein each carbon individually can be substituted with 1 to 2 substituents selected from 1 to 2 halogen, C1 to C6 alkyl, C2 to C4 alkoxycarbonyl or phenyl optionally substituted with 1 to 3 substituents independently selected from W and one of the carbon atoms can be combined into the group C(O) or C(S);
B is H, C1 to C6 alkyl, C4 to C7 cycloalkyl alkyl, C3 to C6 cycloalkyl optionally substituted with 1 to 2 halogens or 1 to 2 CH3; C1 to C6 haloalkyl, C2 to C6 alkenyl, C2 to C6 haloalkenyl, C2 to C6 alkynyl, OR7, C2 to C6 alkoxyalkyl, C2 to C6 cyanoalkyl, C3 to C8 alkoxycarbonylalkyl, CO2R4, C(O)R4, C(O)NR4R5, C(S)NR4R5, C(S)R4, C(S)SR4, phenyl, phenyl substituted by (R14)p, benzyl, or benzyl substituted with 1 to 3 substituents independently selected from W;
J is H, C1 to C4 alkyl or phenyl optionally substituted with W;
K is H or CH3;
q is 0, 1 or 2;
R1, R2, and R14 are independently selected from R4, halogen, CN, N3, SCN, NO2, OR4, SR4, S(O)R4, S(O)2R4, OC(O)R4, OS(O)2R4, CO2R4, C(O)R4, C(O)NR4R5, S(O)2NR4R5, NR4R5, NR5C(O)R4, OC(O)NHR4, NR5C(O)NHR4 and NR5S(O)2R4; or when m, n or p is 2, R1, R2, or R14 can independently be taken together as OCH2O, OCH2CH2O or CH2CH2O, to form a 5 or 6-membered ring, each of which can be independently substituted with 1 to 4 halogen atoms or 1 to 2 methyl groups;
R4 is selected from H, C1 to C6 alkyl, C3 to C6 cycloalkyl, C3 to C8 alkoxycarbonylalkyl, C3 to C6 alkenyl, C3 to C6 alkynyl, C1 to C6 haloalkyl, C3 to C6 haloalkenyl, C1 to C6 alkyl substituted with CN, CO2CH3, CO2CH2CH3, OCH3, OCH2CH3, SCH3, SCH2CH3 or NO2, or R4 is phenyl or benzyl, either optionally substituted with W; or R4 and R5 can be taken together as (CH2)4, (CH2)5 or CH2CH2OCH2CH2;
R5 is selected from H, C1 to C4 alkyl, C3 to C4 alkenyl, C3 to C4 alkynyl or C1 to C4 halo-alkyl;
m, n and p are independently 1 to 3;
W is halogen, CN, NO2, C1 to C2 alkyl, C1 to C2 haloalkyl, C1 to C2 alkoxy, C1 to C2 halo-alkoxy, C1 to C2 alkylthio, C1 to C2 halo-alkylthio, C1 to C2 alkylsulfonyl or C1 to C2 haloalkylsulfonyl;
R6 is H, C1 to C4 alkyl, C1 to C4 haloalkyl, C2 to C4 alkenyl, C2 to C4 haloalkenyl, phenyl optionally substituted with W or benzyl optionally substituted with W;
R7 is H, C1 to C4 alkyl, C2 to C4 alkenyl, C2 to C4 alkynyl, C2 to C4 alkylcarbonyl, C2 to C4 alkoxycarbonyl or C1-C4 alkylsulfonyl;
Q, Y and Z are independently selected from SX;
X is NR8?R9, NR8S(O)aR9, NR8R12 or SR10 R8 and R12 are independently C1 to C6 alkyl, C1 to C6 haloalkyl, C3 to C6 cycloalkyl, C4 to C7 cycloalkylalkyl, phenyl optionally substituted by 1 to 2 substituents selected from W, benzyl optionally substituted by 1 to 2 substituents independently selected from W, phenethyl optionally substituted by 1 to 2 substituents independently selected from W, C2 to C6 cyanoalkyl, C2 to C6 alkoxyalkyl, C3 to C8 alkoxycarbonylalkyl, C4 to C8 dialkylaminocarbonylalkyl; or R8 and R12 can be taken together as (CH2)4, (CH2)5 or (CH2)2O(CH2)2, R9 is F, C1 to C22 alkyl, C3 to C6 cycloalkyl, C3 to C6 cycloalkoxy, C2 to C8 dialkylamino, C1 to C6 haloalkyl, phenyl or phenoxy either optionally substituted by 1 to 2 substituents independently selected from W; C1 to C22 alkoxy, C1 to C4 alkoxy substituted by cyano, nitro, C2 to C4 alkoxy, C4 to C8 alkoxyalkoxy, C1 to C2 alkylthio, C2 to C3 alkoxycarbonyl, C3 to C5 dialkylaminocarbonyl, phenyl or 1 to 6 halogens; or R9 is morpholino, piperidino or pyrrolidino, 1-naphthoxy, 2,2-dimethyl-2,3-dihydrobenzofuranoxy-7 or ON=C(CH3)SCH3;
R10 and R11 are independently C1 to C4 alkyl, C2 to C4 haloalkyl or phenyl optionally substituted by 1 to 2 substituents independently selected from W; or R10 and R
can be taken together as (CH2)2, (CH2)3 or CH2C(CH3)2CH2;
Y' is S or O; and a is 0 to 2.
2. A compound according to Claim 1 wherein:
R1, R2, and R14 are independently R4, CO2R4, halogen, CN, NO2, OR4, SR4, S(O)R4, S(O)2R4 or NR4R5, or when m, n or p is 2;
R1, R2, or R14 can be taken together as OCH2O, OCH2CH2O or CH2CH2O, each of which can be substituted with 1 to 4 halogen atoms or 1 to 2 methyl groups;
R4 is C1 to C2 alkyl, C3 to C4 alkenyl, C1 to C2 haloalkyl, C3 to C4 haloalkenyl or phenyl optionally substituted with halogen;
R5 is H or C1 to C2 alkyl;
X is X1, X2, X3, X4 or X5;
R8 and R12 are independently C1 to C6 alkyl, C1 to C6 haloalkyl, C5 to C6 cycloalkyl, C3 to C8 alkoxycarbonylalkyl, phenyl, benzyl or phenethyl, each optionally independently substituted with W; or R8 and R12 can be taken together as (CH2)4, (CH2)5 or (CH2)2O(CH2)2;
R10 and R11 are independently C1 to C3 alkyl or phenyl;
a is 2;
Formula III is ; ;
; ; or ;
X' is O or S;
t is 0, 1 or 2;
V is O, S(O)q, or NR6;
Z' is O or NR6;
R13 is H, halogen, C1 to C6 alkyl, C2 to C4 alkoxycarbonyl, phenyl or phenyl substi-tuted by 1 to 3 substituents independently selected from W; and g is 0, 1 or 2.
R1, R2, and R14 are independently R4, CO2R4, halogen, CN, NO2, OR4, SR4, S(O)R4, S(O)2R4 or NR4R5, or when m, n or p is 2;
R1, R2, or R14 can be taken together as OCH2O, OCH2CH2O or CH2CH2O, each of which can be substituted with 1 to 4 halogen atoms or 1 to 2 methyl groups;
R4 is C1 to C2 alkyl, C3 to C4 alkenyl, C1 to C2 haloalkyl, C3 to C4 haloalkenyl or phenyl optionally substituted with halogen;
R5 is H or C1 to C2 alkyl;
X is X1, X2, X3, X4 or X5;
R8 and R12 are independently C1 to C6 alkyl, C1 to C6 haloalkyl, C5 to C6 cycloalkyl, C3 to C8 alkoxycarbonylalkyl, phenyl, benzyl or phenethyl, each optionally independently substituted with W; or R8 and R12 can be taken together as (CH2)4, (CH2)5 or (CH2)2O(CH2)2;
R10 and R11 are independently C1 to C3 alkyl or phenyl;
a is 2;
Formula III is ; ;
; ; or ;
X' is O or S;
t is 0, 1 or 2;
V is O, S(O)q, or NR6;
Z' is O or NR6;
R13 is H, halogen, C1 to C6 alkyl, C2 to C4 alkoxycarbonyl, phenyl or phenyl substi-tuted by 1 to 3 substituents independently selected from W; and g is 0, 1 or 2.
3. A compound according to Claim 2 wherein:
R1 is halogen, CN, NO2, OCF2H, OCF3, OCH2CF3, OCF2CF2H, CF3 or when m is 2 then R1 may be taken together as CH2C(CH3)2O or CF2CF2O to form a 5 membered ring;
R2 is H, halogen, CN, NO2, OCH3, OCF2H, OCH2CF3, OCF3, SCH3, SCF2H, SCF3, CF3, OCF2CF2H or phenoxy;
R14 is R2 or CO2R4;
X is X1, X2 or X3;
R8 is C1 to C4 alkyl, CF3, cyclohexyl, phenyl optionally substituted with W or benzyl optionally substituted by W;
R9 is F, C1 to C22 alkyl, C1 to C6 haloalkyl, phenyl or phenoxy optionally substituted by W; C1 to C22 alkoxy, dimethylamino or C1 to C4 alkoxy substituted with NO2, C2 to C4 alkoxy or 1 to 6 halogens;
m, n or p are independently 1 to 2 and one substituent is in the 4-position and B is H, C1-C4 alkyl, CO2R4, C(O)R4 or phenyl optionally substituted by (R14)p.
R1 is halogen, CN, NO2, OCF2H, OCF3, OCH2CF3, OCF2CF2H, CF3 or when m is 2 then R1 may be taken together as CH2C(CH3)2O or CF2CF2O to form a 5 membered ring;
R2 is H, halogen, CN, NO2, OCH3, OCF2H, OCH2CF3, OCF3, SCH3, SCF2H, SCF3, CF3, OCF2CF2H or phenoxy;
R14 is R2 or CO2R4;
X is X1, X2 or X3;
R8 is C1 to C4 alkyl, CF3, cyclohexyl, phenyl optionally substituted with W or benzyl optionally substituted by W;
R9 is F, C1 to C22 alkyl, C1 to C6 haloalkyl, phenyl or phenoxy optionally substituted by W; C1 to C22 alkoxy, dimethylamino or C1 to C4 alkoxy substituted with NO2, C2 to C4 alkoxy or 1 to 6 halogens;
m, n or p are independently 1 to 2 and one substituent is in the 4-position and B is H, C1-C4 alkyl, CO2R4, C(O)R4 or phenyl optionally substituted by (R14)p.
4. A compound according to Claim 3 wherein:
X is X1;
R8 is C1 to C4 alkyl;
Rg i.s C1 to C22 alkoxy;
Formula III is III-1 or III-2;
V is O or CH2;
t is 1; and R13 is H.
X is X1;
R8 is C1 to C4 alkyl;
Rg i.s C1 to C22 alkoxy;
Formula III is III-1 or III-2;
V is O or CH2;
t is 1; and R13 is H.
5. A compound according to Claim 3 wherein:
X is X2;
R8 is C1 to C4 alkyl or phenyl optionally substituted with CH3 or C1; and R9 is C1 to C6 alkyl, C1 to C6 haloalkyl, dimethylamino or phenyl optionally substituted with CH3 or C1.
X is X2;
R8 is C1 to C4 alkyl or phenyl optionally substituted with CH3 or C1; and R9 is C1 to C6 alkyl, C1 to C6 haloalkyl, dimethylamino or phenyl optionally substituted with CH3 or C1.
6. A compound according to Claim 3:
methyl 7-chloro-3,3a,4,5-tetrahydro-2-[[N-[[N-methyl-N-[octadecyloxy)-carbonyl]amino]thio]-N-[4-(trifluoro-methyl)-phenyl]amino]carbonyl]-2H-benz-[g]indazole-3a-carboxylate.
methyl 7-chloro-3,3a,4,5-tetrahydro-2-[[N-[[N-methyl-N-[octadecyloxy)-carbonyl]amino]thio]-N-[4-(trifluoro-methyl)-phenyl]amino]carbonyl]-2H-benz-[g]indazole-3a-carboxylate.
7. An arthropodicidal composition comprising an arthropodicidally effective amount of a compound according to any one of Claims 1 to 6 and a carrier therefor.
8. A method for controlling arthropods comprising applying to them or to their environment an arthropodicidally effective amount of a compound according to any one of Claims 1 to 6.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA 2000130 CA2000130A1 (en) | 1989-10-04 | 1989-10-04 | N-sulfenylated and n-acylated pyrazolines |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA 2000130 CA2000130A1 (en) | 1989-10-04 | 1989-10-04 | N-sulfenylated and n-acylated pyrazolines |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2000130A1 true CA2000130A1 (en) | 1991-04-04 |
Family
ID=4143268
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA 2000130 Abandoned CA2000130A1 (en) | 1989-10-04 | 1989-10-04 | N-sulfenylated and n-acylated pyrazolines |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA2000130A1 (en) |
-
1989
- 1989-10-04 CA CA 2000130 patent/CA2000130A1/en not_active Abandoned
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