CA2000149A1 - Substituted indazole arthropodicides - Google Patents

Abstract

Title SUBSTITUTED INDAZOLE ARTHROPODICIDES

Abstract of the Disclosure Indazole arthropodicides, compositions containing them and a method for controlling arthropods employing these indazoles as the active ingredient. The indazoles have the following general formula wherein Q, X, Y, R1 and m are as defined in the text:

Description

ZOO~ 9 :

Titlç BA-8759-A
SU~STITUTED INr)AZOLE ARTHR~DICIDI~S

: BackqrQund_Q_5h~_Lnvçn~ion U.S. 4,070,365 discloses insecticidal compounds of the formula R~R3 N~
~,C~N~ .;
', ~ ' .,~, .
. . .
~- 20 wherein ;
:~ . . .
R2 and R3 are independently alkyl, cycloalkyl, j :
^ pyridyl or thienyl optionally substituted with halogen, alkyl or nitro, or a phenyl group . .
:` optionally substituted with 1 or 2 .
` 25 substituents selected from halogen, alkyl, -: haloalkyl, cycloalkyl alkylthio, alkoxy, mono ^:i or dialkylamino, nitro, phenyl optionally ;~ substituted with halogen, or cyano;
Y is halogen, NO2, alkyl, haloalkyl, cycloalkyl, :
` 30 alkylthio, alkoxy, dialkylamino, alkylsulfo- .
-~ nyl, acyl, acylamino, cyano, or a phenyl ; optionally substituted with halogen; and ~. .
; X is O or S. ~
'' , :

, ~

2()00'149 .

U S. 4,663,341 discloses insecticidal compounds of the formula ~'; '.
, ' : A~ Y
N~ ~CH2 : N
U~
'.

;
wherein A is unsubstituted or substituted phenyl;
B is unsubstituted or substituted ph~nyl;
U is O, S or NR;
Y is alkyl, carbonyl or phenyl each of which `~ may be optionally substituted; and `~ Z is an organic radical other than hydrogen.
, ~
Vaughan, ~Q ~9L_Çh~m~, ~Q (1955), pages 1619 25 to 1626, discloses 1,5-diphenyl-2-pyrazoline-3-carbo~amide. No utility is given for the disclosed compound which, in any event, does not suggest a compound of the instant invention.

Harhash et al., J, Heterocycli~_Çhem , 21 (1984), at page 1013, discloses the preparation of five pyrazoline compounds, none of which is disclosed - in the instant application. No utility is ~iven for any of said compounds:

., . -.
,'-.

~, .

. . - . . . : . . .. ... . .. . .

.. . . . . . . . . . .

Z0~1~9 . 3 ~.

H where R/Ar are 5~ .6 5 C6H5/C6H5;
N ~ H 2 2 5 6 5;
" 6 5 C(O)NHC6H5/C6H5;
6 5 6 5; and CH3/4-NO2-c6H4-WO 88/900910 discloses insecticidal pyrazolines such as compounds of the formula;
: ' -,~ ' .~ 15 (R2)n~ A

N~
.. ~ I ,_~(Rl)m x ~ ~

. .
...
WO 88/302995 discloses insecticidal pyrazolines . such as compounds of the formula;

~ "~
. 30 ~.

~C--N~ Rl ) m 3 5 ,I ~:

; : ' ,. ' ~ .
.,~, , : Z0001~9 .

~ wherein, :~ 5 Q i~ ~R2)n ,';
~ 15 A is 1, 2 or 3-atom bridge having 0 to 3 carbon ` atoms and 0 to 1 oxygen atom, NR6 group, or .~ S(O)g group, wherein each carbon ~,r;~ individually can be substituted with 1 to 2 substituents selected from 1 to 2 halogen, ~, Cl to C6 alkyl, C2 to C4 alkoxycarbonyl or : phenyl optionally substituted with 1 to 3 substituents selected from W and one of the carbon atoms can be C(O) or C(S).
:~ 25 .~ EP-A-153,127 discloses insecticidal compounds .~ of the formula :; .
.,i, .. , . .
.. ~ .
~;

~, ~N ::
`~ 35 . 0~--.,, I
: "
.'~', .
.; . .
;.' ' '':
~; :

wherein A is unsubstituted or substituted phenyl;
is unsubstituted or substituted phenyl;
: U is O, S or NR;
~ Y is alkyl, carbonyl or a phenyl group; and : 10 Z is cycloalkyl, or a phenyl group.

This application is a cognate of applications bearing U.S. Serial Numbers 07/249,883 and 07/247,690.

f 15 ~Lmmary of the Inven~iQn ~ This invention pertains to the following -- compounds including all of their geometric and -~ stereoisomers, agriculturally suitable salts thereof, agricultural compositions containing them and their 20 use as arthropodicides: ::
, .

,~, ,C--N~ Rl ) m "i 25 .. 1 :
:i~
' :' !::
, .
~:
~ wherein:
Q is ,.'', ~, ~ :

.' '' .

:~ .

-- 2~)~0~49 ~ R~ R"

N--N ( E7~ ) n t~l--N

` Q-l Q-2 , 10 . ~ .

. :
. , ~

5 N~R~

N--N N--N
~^' \ ' ~
~ 2 0 ~ 3 Q ` ` `
. :~

: ,` . .
.~

,i 25 (R~)~R : ~R~R

N--N N--N
' ~ 3, '~;~ ' ' ~5 Q-6 ',, .. 35 ,~, .

,,` :

,:

' . ' ::', . , ' ' ', : .
' ~ ~ ' ' . , .. ` ' . . ~

zn~o l49 G ~ ~ or N-N (R2)n N
:. \ ., Q_7 Q-8 . 15 ;
G is O or S; .
:- A is a 0, 1 or 2-atom bridge comprising 0 to 2 . .
: carbon atoms, 0 to 1 oxygen atoms, 0 to 1 . S(O)q groups or 0 to 1 NR6 groups wherein each carbon atom is optionally substituted with 1 to 2 substituents selected from Ra;
~3 is H, Cl to C6 alkyl, C3 to C6 cycloalkyl i optionally substituted with 1 to 2 halogens !i or 1 to 2 CH3, C4 to C6 cycloalkylalkyl, C
.i; 25 to C6 haloalkyl, C2 to C6 alkenyl, C2 to C6 alkynyl, C2 to C6 alkoxyalkyl, C2 to :
C6 cyanoalkyl, C3 to C8 alkoxycarbonylalkyl, - CO2R3, C(O)R3, C(O)NR3R4, C(S)N~3R4, C(S)R3, :::
x C(S)SR3, phenyl, phenyl substituted with (R5)p, benzyl, benzyl substituted with 1 to 3 .~. substituents independently selected from W, or OR7 when Q is Ql to Q7;
W is halogen, CN, NO2, Cl to C2 alkyl, Cl to C2 haIoalkyl, Cl to C2 alkoxy, Cl to C2 halo-alkoxy, Cl to C2 alkylthio, Cl to C2 halo-alkylthio, Cl to C2 alkylsulfonyl or Cl to C2 . haloalkylsulfonyl;
' -.,, :.:

2no~

Rl, R2.and R5 are independently selected from R3, halogen, CN, N3, SCN, NO2, OR3, SR3, SOR3~ S2R3~ OC()R3, OSO2R3, CO2R3, C(O)R3, C(O)NR3R4, SO2NR3R4, NR3R4, NR4C(O)R3, OC(O)NHR3, NR4c(o)NHR3 and NR4S2R3' or when m, n or p is 2, Rl, R2 or R5 can be -OCH2O-, -OCH2CH2O-, or -CH2CH2O-, each of which can be substituted with 1 to 4 halogen atoms or 1 to 2 methyl groups;-R3 is H, Cl to C6 alkyl, Cl to C6 haloalkyl, C2 to C6 alkenyl, C2 to C6 haloalkenyl, C2 to C6 :
alkynyl, C2 to C6 haloalkynyl, C2 to C6 .
.~ alkoxyalkyl, C2 to C6 alkylthioalkyl, Cl to : C6 nitroalkyl, C2 to C6 cyanoalkyl, C3 to C8 alko~ycarbonylalkyl, C3 to C6 cycloalkyl, . C3 to C6 halocycloalkyl, phenyl, benzyl, or ;~ 20 phenyl or benzyl substituted with 1 to 3 -~ substituents independently selected from W;
`~ R4 is H, Cl to C4 alkyl or R3 and R4 can be ^.. ~. taken together as (CH2)4, (CH2)5 or , ~CH2cH2OcH2cH2);
:~ 25 R6 is H, Cl to C4 alkyl, Cl to C4 haloalkyl, C2 lj to C4 alkenyl, C2 to C4 haloalkenyl, C2 to C4 .:
.^~ alkynyl, phenyl optionally substituted with ~ W, or benzyl optionally substituted with W;
-. R7 is H, Cl to C4 alkyl, C2 to C4 alkenyl, C2 to C4 alkynyl, C2 to C4 alkylcarbonyl, C2 to C4 alko~ycarbonyl;
,. ~.
'~
. ~;

~ .

~ .

... .

,~ , . :. . . . :

~; ~ , . :, , . . -Ra is independently selected from H, Cl to C6 alkyl, C2 to C4 alkoxycarbonyl and phenyl ::
optionally substituted with 1 to 3 substi-tuents independently selected f rom W;
X is O or S;
n is 1 to 2;
m i s 1 t o 3;
p is 1 to 3;
: q is 0 to ~;
Y is H~ C 1 to C6 alkyl, C2 to C6 alkoxyalkyl, CHO, C2 to C6 alkylcarbonyl, C2 to C6 ;; alkoxycarbonyl, C2 to C6 haloalkylcarbonyl, ~: 15 Cl to C6 alkylthio, Cl to C6 haloalkylthio, phenylthio, phenylthio substituted with 1 to . 3 substituents independently selected from W, or S-J;

2 0 -~ lR 10 ~ " ~Y lR 11 J is NR8CRg, NR85(O)tRg, NR8~y R 8 ~10 ~ ~ J4 :~, Q Q~OR 1 O
CRg ~ORll N~8R12 or SRlo ~;, ~ J~ ~lz 'I8 R8 and R12 are independently selected from C
to C6 alkyl, Cl to C6 haloalkyl, C3 to C6 cycloalkyl, C4 to C7 cycloalkylalkyl, phenyl optionally substituted with 1 to 2 substi-tuents independently selected from W, benzyl ; optionally substituted with 1 to 2 substituents independently selected from W, 35 phenethyl optionally substituted with 1 to 2 ~.
.; substituents independently selected f rom W, C2 to C6 cyanoalkyl, C2 to C6 alkoxyalkyl, C3 : ' . . .

,, ., ..... . . .. .. ., . . . . ., ;., . ~. ,., .. ,, , .~ ~ , . .. .. .. . ... ..

to C8 alkoxycarbonylalkyl and C4 to C8 di-alkylaminocarbonylalkyl, or R8 and R12 can be taken together as (CH2)4, (CH2)5 or (CH2)2~(CH2)2;
Rg is F, Cl to C22 alkyl, Cl to C6 haloalkyl~
Cl to C22 alkoxy, C2 to C8 dialkylamino~
piperidinyl, pyrollidinyl, morpholino, Cl to C4 haloalkoxy, Cl to C4 alkoxy substituted with cyano, nitro, C2 to C4 alkoxy, C4 to C8 alkoxyalkoxy, Cl to C2 alkylthio, C2 to C3 alkoxycarbonyl, C3 to C5 dialkylaminocarbonyl or phenyl, or Rg is phenyl optionally substi-tuted with 1 to 2 substituents independently ~-selected from W, or phenoxy optionally substituted with 1 to 2 substituents independently selected from W;
Rlo and Rll are independently selected from C
~` 20 to C4 alkyl, C2 to C4 haloalkyl and phenyl optionally substituted with 1 to 2 substi-tuents independently selected from W, or Rlo and Rll can be taken together as (CH2)2, (CH2)3 or CH2c(cH3)2cH2;
t is 0 to 2; and Yl is O or S.

In the above definitions, the term "alkyln, used ; either alone or in compound words such as ~alkylthio"
or "haloalkyl~, denotes straight chain or branched alkyl such as methyl, ethyl, n-ProPYl~ isopropyl or the diferent butyl, pentyl, hexyl isomers.
Alkoxy denotes metho~y, ethoxy, n-ProPyloxy, iso-propyloxy and the different butoxy or pentoxy isomers.
Alkenyl denotes straight chain or branched - alkenes such as vinyl, l-propenyl, 2-propenyl, 3-propenyl and the different butenyl, pentenyl and hexenyl isomers.

O ' ~ - c 200~149 11 ~

Alkynyl denotes straight chain or branched S alkynes such as ethynyl, l-propynyl, 2-propynyl and the different butynyl, pentynyl and he~ynyl isomers.
Alkylthio denotes methylthio, ethylthio and the different propylthio and butylthio isomers.
Alkylsulfinyl, alkylsulfonyl, alkylamino, and 10 the like, are defined analogously to the above e~amples.
Cycloalkyl denotes cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.
The term "halogen~, either alone or in compound 15 words such as ~haloalkyl~, denotes fluorine, chlorine, bromine or iodine. When used in compound words such as "haloalkyl" said alkyl may be partially or fully substituted with halogen atoms, which may be the same or different. Examples of haloalkyl include CH2CH2F, 20 CF2CF3 and CH2CHFCl. The terms "halocycloalkyl", ~haloalkenyl~ and "haloalkynyl~ are defined analogously to the term ~haloalkyl".
The total number of carbon atoms in a substi-tuent group is indicated by the "Ci to Cj n prefix 25 where i and j are integers. For e~ample, Cl to C3 alkylsulfonyl would designate methylsulfonyl through propylsulfonyl; C2 alkoxyalkoxy would designate OCH2OCH3; C4 alkoxyalko~y would designate the various isomers of an alko~y group substituted with 30 a second alko~y group containing a total of 4 carbon atoms, e~amples including OCH2OCH2CH2CH3 and OCH2CH2OCH2CH3; C2 cyanoalkyl would designate CH2CN
and C3 cyanoalkyl would designate CH2CH2CN and CH(CN)CH3; C2 alkylcarbonyl would designate C(O)CH3 35 and C4 alkylcarbonyl would include C(O)CH2CH2CH3 and C~O)CH(CH3)2; and as a final e~ample, C3 alko~y-carbonylalkyl would designate CH2CO2CH3 and C4 alkoxy-carbonylalkyl would include CH2CH2CO2CH3, CH2CO2CH2CH3 and CH(CH3)CO2CH3.

,~ . .
~,.

: . ,. , . . .. . ~ . . . .. : : . ., . . - :
. . .

-`` ` 200~0149 : Preferred Compounds A are those of Formula I
wherein:

A is CRaRa, S, O or NR6;
B is H, Cl to C6 alkyl, Cl to C6 haloalkyl, C2 to C6 alkenyl, C2 to C6 alkynyl, C2 to C6 alkoxyalkyl, C3 to C8 alkoxycarbonylalkyl, CO2R3, C(O)R3, C(O)NR3R4, C(S)NR3R4, C(S)R3, C~S)SR3, phenyI or phenyl substituted by : (Rs)p;
W is Cl, F, Br, CN, CF3, Cl to C2 alkyl, C
to C2 alkoxy, OCF2H, OCF3 or NO2;
; 15 R2 is R3, halogen, CN, SCN, NO2, OR3 or SR3;
- R3 is H, Cl to C4 alkyl, Cl to C2 haloalkyl, C3 to C4 alkenyl, C3 to C4 haloalkenyl, propargyl, phenyl, benzyl, or phenyl or benzyl substituted with one of F, Cl, ~r, CF3, OCF3, OCF2H or NO2;
p is 1 or 2;
m is 1 or 2;
X is O; -.. Y is H, Cl to C4 alkyl, SCH3, SCC13, SO2CH3, SC6H5~ 2-NO2-C6H4S, C(O)CH3, C(O)CH2CH3, C(O)CF3; CO2CH3~ C2CH2CH3, or S-J;
.~ J is Jl~ J2~ J3, J4 or J5;
R8 and R12 are independently selected from C
to C6 alkyl, Cl to C6 haloalkyl, C5 to C6 cycloalkyl, C3 to C8 alkoxycarbonylalkyl, .
phenyl, benzyl and phenethyl, each phenyl, benzyl and phenethyl optionally substituted ` with W, or, R8 and R12 can be taken together i~ as (CH2)4, ~CH2)s or (cH2)2o(cH2)2;
,~ 35 Rlo and Rll are independently selected from Cl -:
to C3 alkyl or phenyl; and .
t is 2.

.' ~,.
. . . .

-- Z00!~9 Preferred Compounds B are Compounds A wherein:

. B is H, Cl to C4 alkyl, C3 to C4 alko~ycarbonyl-:~ alkyl, CO2R3, C(O)R3, phenyl or phenyl substituted with (R5)p;
: 10 Rl is halogen, CN, SCN, NO2, OR3, SR3, SO2R3, CO2R3, C(O)R3 or is R3 with one substituent in the 4-position;
R5 is H, R3, halogen, CN, SCN, NO2, OR3, SR3, ;~ SO2R3, C(O)R3, OSO2R3~ C2R3~ C(O)R3~
C(O)NR3R4, SO2NR3R4 or NR3R4; or, when m or p :~ is 2;
`, Rl and R5 can be -CH2C(CH3)2O-, :
OCH2CH2O-, OCF2CF2O- or -CF2CF2O-; .
~; R3 is Cl to C4 alkyl, Cl to C2 haloalkyl, C3 to C4 alkenyl or propargyl; ~
` R4 is H or CH3; .; .
`~ Ra is H, CH3, CO2CH3 or CO2CH2CH3;
m and p are independently 1 or 2 and one substi- ~
tuent is in the para-position; :~ .
Y is H, CH3, COCH3, CO2CH3 or S-J; ;
~ J is Jl or J2;
-`~ R8 is Cl to C4 alkyl or phenyl optionally substi-. tuted with Cl or CH3;
Rg is Cl to C20 alkyl, Cl to C20 alkoxy, Cl to 30 C6 haloalkyl, dimethylamino, phenyl option-ally substituted with Cl or CH3, or, Rg is Cl to C4 alko~y substituted with C2 to C4 alko~y .
or 1 to 6 halogens; and .:
G is S.

. Preferred Compounds C are Compounds B wherein:
Rl is Cl, F, Br, CF3, CN, OCF3, OCF2H, OCF2CF2H , or SCF2H; i;
.,".
.

-"` 2000~9 ; R2 and R5 are independently H, Cl, F, ~r, CN, CF3, CH3, OCHtCH3)2, OCF2H, OCF3, SCH3, SCF2H, NO2 or OCH2CF3;
B is H, CH3, CH2CH3, CH(CH3)2~ CO2CH3~ C2CH2C 3' phenyl or phenyl substituted with (R5)p; and . Ra is H or CH3.

. 10 Preferred Compounds D are Compounds C wherein:
.~ A is O or CH2;

Preferred Compounds E are Compounds D wherein:
.~ Q is Q~
~:: 15 Preferred Compounds F are Compounds D wherein: `
Q is Q-2;
:'` .
`~ Preferred Compounds G are Compounds D wherein: -Q is Q-3;
: . .
Preferred Compounds H are Compounds D wherein:
ï Q is Q-4;
-Preferred Compounds I are Compounds D wherein: ~-Q is Q-5;
~ "
~` Preferred Compounds J are Compounds D wherein: :
'~ Q is Q-6; :
~` Preferred Compounds X are Compounds D wherein: :
- Q is Q-7;
', ' '.
Preferred Compounds L are Compounds D wherein:
~' 35 Q is Q-8;

., ~ .

:,. , _ Z00~49 ::

.
Specifically pre~erred compounds are:

M) methyl 3,3a,4,5-tetrahydro-2-[[[4-trifluoro-methyl)pheny]-amino]carbonyl]-2H-pyrazolo[3,-4-f]-quinoline-3a-carboxylate, a compound of . Preferred E;

N) methyl 3,3a,4,5-tetrahydro-2-[[[4-trifluoro-: methyl)phenyl]-amino]carbonyl]-2H-pyrazolo[4,-: 3-h]-quinoline-3a-carboxylate, a compound of : Preferred H;
:~
O) methyl 7-chloro-3,3a,4,5-tetrahydro-N-[[[4-` trifluoromethyl)phenyl]amino]carbonyl]-2H-thieno [2,3-g]-indazole-3a-carboxylate, a compound of Preferred I;
.', ' -:
P) methyl 7-fluoro-3A,4-dihydro-2-[[[4-(tri-fluoromethyl)-phenyl]amino]carbonyl]-3H-~:~ pyrazolo[5,1-c]-[1,4]benzoxazine-3a-carboxyl-.~ ate, a compound of Preferred L; and .~j . .
~ 25 Q) 7-chloro-3A-(4-fluorophenyl)-3A,4-dihydro-N-i~ [4-(trifluoromethyl)phenyl]-3H-pyrazolo[5,1-c~[1,4]-benzoxazine-2-carboxamide, a compound .
of Preferred L.
,:
: 30 Hereafter, in the specification and claims, the various geometric isomers, stereoisomers and . agriculturally suitable salts of each and every compound of the invention depending on context, is/are . included in the term "compound(s). n :
. 35 :
~ ail~-Qf--~k-QI-nv-~-n-~LQ~
For descriptive purposes, Q-l, where Ra is H, : -will be used as a representative value of Q, when Q is , ~ ~ .
", ' .".

`` ` ' :. .' i `' , ` ' , ` '., :, . ' - ~ ` `, .; ` : ' "' ' 200~4~ .

.
Q-l through Q-7, in the discusssion that follows and will be referred to by the following numbering system:

, 0 7 ~ 3 N--N
.`~ 1 2 Compounds of Formula I can be prepared by the reaction of aryl isocyanates of Formula II and substituted indazoles of Formula III as shown in Scheme I. Typical reactions involve the combination . 20 of equimolar amounts of II and III in conventional organic solvents including ether, tetrahydrofuran .~ (THF), methylene chloride, chloroform and benzene.
The reaction can be run at temperatures ranging from about -20C to lOO~C with temperatures in the range of .
about -10 to 30C generally preferred.
~H.EME 1 ' -.. . . .
: 30 .:, ~ ,NCO N A
~ (R,);~ ~ (R2)~) N N

-. 35 I I I I I ( Q= Q- 1 ) ''.;
.` . :

,: ` . . . . . . .. . . ..

.: : ` : :: :: : :. : ~ ,:, . .

`-- 2~Q~4~

17 ~ .

Substituted indazoles of Formula III, where B
is equal to H, can be prepared by the reaction of hy-drazine with an a, B-unsaturated ketone of Formula IV
(or their precursors~ by procedures well documented in the chemical literature (Scheme 2). For a review of pyraz~line synthesis, see El-Rayyes and Al-Awadi, 10 Synthesis, 1028 (1985). For literature describing the synthesis of 3,4- and 3,5-disubstituted pyrazolines, which can be applied to the synthesis of compounds of Formula III, where B is H, see U.S.
Patent 3,991,073 and U.S. Patent 4,070,365.

:.
.'~. . ,. ' 20 ( R2 ) n ~ b NH2 NHz I I I ~ -,,' ', ' I V ( B= H) :.
Preparation of compounds o~ Formula I, where B ~:
. is other than H, OR7, phenyl or substituted phenyl :
can be achieved by metallation of the 3a position of ~ 30 Formula I (where ~ is H~ followed by reaction with a suitable electrophile as depicted in Scheme 3. Pro- .
. cedures for the related transformation of 4-substi-- tùted pyrazolines to 4,4-disubstituted pyrazolines are reported in U.S. Patent 4,663,341 and can be 35 applied to substituted indazoles of Formula I. ::
Metallation can be accomplished by deprotonation with :
a strong base, in a suitable solvent and at tempera-. , .

,:

tures ranging from -78C to 100C. Useful bases for this reaction include lithium dialkylamides such as lithium diisopropylamide and lithium tetramethylpiper-idide and alkyl lithium reagents such as n-butylli-thium and s-butyllithium. Deprotonation of compounds of Formula I, where B is equal to hydrogen, will require two equivalents of base when Y is equal to hydrogen. The reaction can be conducted in many conventional organic solvents and in certain instances a cosolvent may be useful. Suitable solvents include diethylether, tetrahydrofuran, tetrahydropyran, benzene and the like. Suitable electrophilic reagents for reaction with the metallated Formula I compounds include alkyl and -~ substituted alkyl halides, alkyl chloroformates, acyl halides, isocyanates, dialkyl carbamoylhalides and related electrophiles which will be known to those skilled in the art.

: .
I ~ I
(B is H) 2. E ~B is other than H, O~7, phenyl or substi- `
tuted phenyl and E+ is an electrophilic reagent) :
An alternative procedure for introduction of the 3a substituent, which in certain instances is preferred over that of Scheme 3 due to higher yields and/or greater ease of synthesis, proceeds via the intermediacy of Compound V, wherein the 2-nitrogen has been derivatized with a suitable protecting qroup. Deprotonation with a strong base such as lithium diisopropylamide, typically in stoichiometric quantities, followed by reaction with any of the :', .. . : , . . ~ . . . . ~ .: .

~o~l 4~

previously described electrophiles provides compounds of Formula V where ~ is other than hydrogen, OR7, phenyl or substituted phenyl. Removal of the nitrogen protecting gro-~p provides the required Formula III intermediate. Nitrogen-protecting groups are well documented in the chemical literature, as are procedures for their preparation and cleavage.
E~amples include acetyl, trifluoroacetyl, benzoyl, substituted benzoyl, alkoxycarbonyl, benzyl and substituted benzyl. For a review see Greene "Protective Groups in Organic Synthesis" (New York:
- John Wiley and Sons, 1981) pp. 218 to 287.
~S~EME 4 !

.~ ,.
.

1. PC
I I I ( R2 ) n {~9 'I I I

PG
2 5 ( 13 19 H) V ( 9 is ot h~r t h~n H.
OR7, Ph or 9 ub. Ph) .

Note: E+ is an electrophile and PG is representa-tive of a suitable nitrogen-protecting group.
'.
3 5 Formula III compounds where B is equal to hydroxy are prepared by the reaction of hydrazine with a suitably substituted epoxide of Formula VI

~.:

., . .. ., - . .

. . . . - :. . . - : ~

Z~00~4~

(Scheme 5). The epoxides are available from the enones of Formula IV by procedures. known in the art, the most widely employed method being epoxidation via the use of alkaline hydrogen peroxide (see, e.g., Wasson and House, Org. Syn., Coll. Vol. 4, 552 (1963)).
Compounds of Formula I where B is equal to OR7 and R7 is other than hydrogen, can be prepared from the Formula I compounds where ~ is equal to hydroxy via reaction with electrophilic reagents such as alkyl halides, acyl halides, alkyl chloroformates, chlorosulfonates, isocyanates and dialkyl carbamoyl-halides. Those skilled in the art will recognizethat conditions necessary for this transformation including solvent, catalyst, temperature, etc., will vary with the specific electrophile chosen and the specific Formula I compound used.

, , .
.
2 5 H202 ~NyA~ NH2NH2 ( Rz ) ,,~
O

, VI ( E3 i~ OH) 3~

.
- Compounds of Formula III where B is phenyl or substituted phenyl can be prepared by reactio~ of a ketone of Formula IX, where L is a suitable leaving group such as chloride, bromide, tosylate or mesylate, with hydrazine. The Formula IX compounds ., .

-- Zn~Q1.4~

.. . .
are in turn prepared from the compounds of Formula :
VII in a two-step process involving first an aldol reaction of formaldehyde to produce the aldol product of Formula VIII followed by conversion of the hydroxyl group to a leaving group L. As an example, treatment of the Formula VIII compound with methane-sulfonylchloride in the presence of an amine base produces the Formula IX compound where L is mesylate.
; SCHEME 6 .. :

`
(R2)nf~ph CAH~O (R2)n~ ~Ph O O OH

~, 20 VII VIII

~,0 .,` ', ',' thCl ~A~NH2N~2 Er3N ~Ph III
:~ L
IX ( 13 19 Ph) (L ~9 O~b) . ~ .
.

~-' ' , ~ '' ' ,' .' .

.

. ~ : .
. . . ~ ~ -,G,~ r~ L~

The a-methylene ketones of Formula IV can be prepared from the ketones o~ Formula X by a variety of procedures well documented in the literature. For e~ample, treatment of X with with tetramethyldiami-nomethane and acetic anhy~ride produces the Formula IV
compound directly. Another useful procedure is to treat the Formula X compound with formaldehyde under conditions of a Mannich reaction. The dialkylamino group can be eliminated Ln situ upon treatment with base to form the intermediate of Formula IV. -. .
lS
' -. ~N~A~ ( ~Sa2N)2CH2 1. (R2)n~J AC20 IV
20ll X
."~

.. 25 "~ , .
'' ~-M~nnic h ~N~A~ b~s e 3 0 Re~ c t l o n ~ I V
o NR2 .'' ,:
'; ' ~ 35 : ' '. :
,, , ,~,:.:

., .
: . .
- . ;. , .. - ., . - - , .- . . . , ~ . . . , .:

, ... ,, . , , , . . . . .,: . . . . . .... ... . . .

00.14~

Those skilled in the art will recognize the intermediates of Formula X as substituted quinolones.
Isoquinolones and the isomeric benzothiophenones used for preparation of compounds of Formula I, where Q is Q-2 through Q-7, are also known in the chemical literature as are procedures for their preparation.
A few selected reerences include: where Q is Q-l see J. Chem. Soc., Perkin I, 975 (1976), where Q is Q-2 see J. Amer Chem. So~, 107, 4998 (1~85), where Q is Q-3 see J. Org ~Chem. 93, 966 (1978), where Q is Q-4 see J. Het. Chem. 15, 249 (1978), when Q is Q-5 or Q-7 see Tetrahed~on Letters, 2885 (1975) or ~, ~eterocyclic Chem., 17, 87 (1980), and where Q is Q-6 see Bull. Soc. Chim. Fr., 335 (1973).
An alternative method for preparing compounds of Formula I, where Q is Q-l through Q-7, involves ;~ intramolecular cyclization of hydrazone XI to produce the N-phosphorylated dihydropyrazole XII. The phosphorus group can then be removed under acidic ~; conditions and neutralized with base to yield the ,~ substituted indazoles of Formula III.
; SCHEME 8 - ~', B
R ) ~ h Iog~anat ing ~N~A 1. H
C ~ n ~ / J ¦ ~¦E3 III
b~e / ~> 2. neutrtlllze NNP ( R2 ) n I ~R
O Y :. , ~ XI XII
', :' ', .,. ''.,- .,.. ~' ' , . : ' - : . , . : - .

,, , ' : , -~` Z~l~C~

2q wherein:
Rx and Ry are independently selected from Cl to C4 alkyl and Cl to C4 alkoxy.

The intramolecular cyclization can be conducted by gradual addition of a moderately reactive halogenating agent such as N-chlorosuccinimide to a mixture of a base, such as triethylamine, and the . compound of Formula XI in a dry inert solvent such as ether, dichloromethane or toluene. Alternatively, ` 15 when Q is Q-5, Q-6 or Q-7, the base can be added ; gradually to a mixture of the halogenating agent and compound XI. It is preferable that the concentration of reactant be kept relatively low (0.01 to 0.5 ~) and that the compound being added to the reaction mixture is added gradually to avoid competing side reactions which occur at higher concentrations. For ~` optimum yields, it is also important to maintain anhydrous conditions.
Hydrolysis of the phosphorus group is best j 25 accomplished by treatement of XII with 1 to 5 '! equivalents of a strong acid such as hydrochloric, sulfuric or p-toluenesulfonic in a suitable solvent such as methanol, ethanol or tetrahydrofuran, optionally containing about 0.1 to 10 equivalents of water. The reaction can be conducted at temperatures generally ranging from about 20 to 100C with the :
reflu~ temperature of the solvent being generally !~
preferred. Once the reaction is complete, th~e acid '~ salt can be precipitated by cooling to 0C, or if it does not precipitate, the solvent can be removed and ether added to facilitate crystallization. The acid salt of III can then be neutralized with an inorganic base such as sodium carbonate or sodium bicarbonate ,,. " .
.',. . ..

.. .,.. . . ... . . . . . .. ~ . . , . . ,.. . . ~, . . .: ,. . :

to give the ~ree base III. In some instances, it is preferable to convert the acid salt of III directly to compounds of Formula I by addition of an aqueous solution of an inorganic base to a suspension ~ the salt III in an organic solvent such as tetrahydrofuran, followed by addition of the ff' isocyanate I I .
Compounds of Formula XI are prepared by - condensation of an aldehyde of Formula XIII with a phosphorus hydrazid of Formula XIV.

.:
~ 15 .:~

H~NNliP XI

` XIII XIV
~`
,.~ ;
This reaction is typically run in an inert organic solvent. Alcohol solvents such as methanol and ethanol and ether solvents such as tetra-hydrofuran and diethyl ether are generally ~` 30 preferred. The reaction can also be conducted with a catalytic amount of acid such as p-toluenesul~onic acid although typically acid catalysis is not necessary. The products of Formula XI generally precipitate from the reaction mi~ture as they are formed.
Starting materials of Formula XIII and XIV can be prepared by analogy with procedures known in the ~` art.

., .
., .

'' , , ' Compounds of Formula I, where Q is Q-8, can be obtained by the reaction of activated carbonyl or thiocarbonyl compounds of Formula II with substituted anilines in the presence or absence of an acid acceptor or suitable condensing agent. Methods for performing this transformation are well known in the art; see, Zabicky, "The Chemistry of the Amides", Interscience, 1970.
One particularly useful method involves the '~
chlorination of an acid derivative (XV, Xl = OH) with ; thionyl chloride or another chlorinating agent followed by treatment with an aniline (XVI) in the presence of an acid acceptor such as an amine base, - - preferably triethylamine. Suitable solvents for the chlorination reaction are inert to hydrogen chloride `~ and include benzene, toluene, and dichloromethane.
` 20 Preferred temperatures for this process are Erom 20 to 100C with temperatures between 20 and 80C being particularly preferred. The latter reaction can be carried out in many different inert solvents such as - dialkylethers, chlorinated hydrocarbons, and aromatic ' -.
; 25 hydrocarbons. While temperatures at or below 25OC
are preferred, higher temperatures can also be ~- employed. These reactions are normally run at atmospheric pressure, but can also be carried out at elevated pressures.
~

: :
,'. ~ .

`, ,~ :
.~ . . .

, ~ -- ~ . - . . - . ~ . . .: :

2 ~

' ' :
~.CHEME lQ

., .

~A~

10 (R2)n N~ (Q = Q-8) ' ~1 XVI , . ~

XV
Xl = Cl. E~r, OH. OR3 .:
. - . . .

.,, ' .
- 20 Esters of Formula Xv (Xl Cl to C6 alkoxy) can be converted directly to compounds of Formula I
(Q~Q-8) in several ways. In the presence of Lewis '~
acids such as AlMe3, anilines react readily with :~ esters of Formula XV. The reaction is best carried out at room temperature to 120C. Suitable solvents . include dichloromethane, 1,2-dichloroethane, and i toluene. The method described by Weinreb et al., Organi~ Svnthesis, ~2, 49, (1982), proceeds best with esters of lower alcohols such as methanol or ethanol.
` 30 Acids of Formula XV (Xl . O~) can be converted directly to compounds of Formula I by use of coupling agents known in the peptide art in conjunction with j anilines. Coùpling agents include dicyclohexylcarbo-'~ diimide (DCC), N-hydroxysuccinimide, 2-chloro-N-35 methylpyridinium iodide, carbonyl diimidazole, or ;
other agents capable of activating an acid function , . . .
!~

2~ ; ~4~

or acting as a dehydrating agent. These and other methods are described in Gross et al., ~The Peptides,"
3 Vols., Academic Press, New York, 1979 to 1981.
Compounds of Formula I (Q=Q-8) and ;ntermediates ; of Formula XV can also be obtained by the intramolecular dipolar cycloaddition reaction of nitrile-imines, generated from substituted phenylhydrazones of Formula XVII (Scheme 11). The presence of an acid acceptor (generally an amine base, ;~ for e~ample, triethylamine) is necessary for the formation of the nitrile-imine. Suitable solvents include but are not restricted to benzene, toluene, 1,2-dichloroethane, chloroform, and tetrahydrofuran.
The reaction can be carried out at temperatures ranging from 20 to 120C with the relative reactivity of the alkene moiety governing the required ~ -temperature for a given example.

.
.'~ ' .
~ . :

,~, 2 5 A~b Accept or ~J~N XV or I

X3;~ ~~ R~ )m XVl I X~

.: - -i: .

; ~ , ' , 2 ~

The required hydrazones of Formula XVII can be 5 synthesized by the Japp-Klingemann reaction (Scheme 12). The coupling of diazonium salts with active methylene compounds is known. The more specific coupling of chloroacetoacetic acid derivatives of Formula XVIII with diazotized anilines of ~ormula XVIV
10 containing alkenyl substituents is described by Padwa et al. in J. Ora. ~h~m., 43, 1664 (1978) and J. Org.
~h~m~, 46, 1402 (1981). A similar process for this type of aniline is described by Garanti et al. in ~
Org. Chem. , ~2, 1389 (1977), and J. Chem. ~o~, Perkin 15 I, 2245 (1981)-: , NH~ l l N~
~ 20 ~ m ON~ ~ X~I
. R2 ( n~ X~
.
XVIV XVIII ~(Rl)m X3 = ~

, The anilines o Formula XVIV can be sbtained by ` 35 the reduction of aromatic nitro compounds of Formula XX (Scheme 13). There are many methods known for this trans~ormation. See, March, ~Advanced Organic Chemistryn, 1985, Wiley, page 1103-1104. A
particularly suitable method involves the treatment of x!r~$~

- the nitro compound with tin (II) chloride in alcoholic solvents. Refer to Bellamy et al. T_~rah~dL~n L~QL~, 1984, 839.

~:
: 10 :: 1 ~A~ Reduct ion :
15 ~ ~ XVIV

( R2 ) n ," XX

Nitro compounds of Formula XX containing a heteroatom in the alkenyl chain can be obtained by ~ alkylation reactions (Scheme 14). Treatment of a ;1 substituted phenol, thiophenol, or aniline of Formula XXI with an acid acceptor and an allyl or homoallyl halide or sulfonate of ~ormula ~XII gives compounds of ~ -Formula XX as products. Preferred acid acceptors for the process are inorganic ~ases such as potassium carbonate. Preferred solvents include 30 dimethylformamide, dimethylsulfo~ide, methylethyl ~ ,~
ketone, and ethanol. The reaction is generally ;
carried out at room temperature, but higher temperatures may be necessary in some cases. .
Alternative methods for these nitro compounds of Formula XX have been described by Oae et al. in Bul~.
Chem. Jap., 54, 2374 (1981).
.~, . . .

. -. : . ~ , 2 ~ L 4 ~

. ~ .

N2 ~\X~
~AH ~ XX
," 1 0 ~J
R2n -' ` XXI XXII
: X4 = ~-. Cl, OS02Et3 ` 15 A = S, O, NR~
'"'~ ' i~ 20 Anilines of Formula XVIV containing sulfur can be obtained by alkylation on the sulfur of Formula .~~ .
XXIII (Scheme 15). The conditions which favor this process are alcoholic solvents and sodium hydroxide or sodium alkoxides as bases. The reaction is generally ^~! 25 carried out using allylic halides of Formula XXII at `;.3 20 to 80 C in lower alcoholic solvents, preferably ,` ethanol.

. ~, ~;
;

:.
.`J
, . .

-''-,; .:
" , ,, , ' . .

2 ~ L ~! ~

S
' ~H XXII XVIV
. 10 ~ Acld Ac c e pt o r ( R2)Z
.
XXIII

Anilines of Formula XVIV which do not contain a heteroatom in the alkenyl portion can be synthesized ,~ by the Claisen rearrangement (Scheme 16). The thermal ~f 70 and acid catalyzed rearrangement of N-allylanilines of 3 Formula XXIV has been described by Hansen et al. in Helv. Chim. Acta., 60, 978 (1977).
~ SCHEME 16 `;-, 25 ,c ~. '.
v .
HN--f~ NHz ~ ot [~3 2)2 2) Acid C~ly~t XXIV XVIV
" 35 ,,, : i'.'.-,' ~.
:, .',' z~ ; a"~

The hydazonyl halides of Formula XVII (A,S, q-1 5 or 2) in which a sulfo~ide or sulfone are present may be obtained by thç o~idation of the corresponding sulfide of Formula XVII (A~S, q.O~ (Scheme 17).
O~idation of hydrazones of Formula XVII (A-S, q.O) by hydrogen peroxide in acetic acid is known. See Zecchi 10 et al., J. C~e~ Res. 1887 (1986). By modifications of the amount of oxidant, reaction time and temperature the product obtained can be specifically the sulfoside of Formula XVII (A~S, q~l) or the sulfone of Formula XVII (A~S, q-2).

.~.
o o 2 0 N~NH ~ o~lld~nt N~NH
02) , ~f ~b H2 (R2)n (R~)n XVIl (A~) Xr~I (A=S(O)q) q = 1 or 2 '~' :, .

:- '.
`; Cycloaddition of the hydrazones of Formula XVII
(A~S, q~O) proceeds only in low yield. Synthesis of 35 sulfur containing compounds Xv (A-S, q-O) can be accomplished by reducing the sulfoxides of Formula XV
(A.S, q.l) (Scheme 18). Many reagents are known in the art to reduce sulfo~ides. See March, ~Advanced Organic Chemistry~, 1985, Wiley, page 1108. One .
, -. .... . . . : - . -, . .. : ,~, ,. :-. .. . . . .. .

particularly useful method uses titanium (III) chloride at room temperature and was described by Ho in ~Yn~h~ic C.Qmm., 3, 37 (1973).
SCHEME 1.~

,: :

O , Reduct lon C~t~ly~t ~ ~S~

~X~ ~X~

XV (A=S(O)) XV (A=S) .. 20 .. ~ .

Xl ' OR3~ ~ X - O, S

` I or XV I or XV -: -. 30 Compounds of Formula I, where Y is H and Q is Q-l through Q-8, can be converted to other compounds !' . ' of Formula I by alkylation, acylation, and sulphenylation reactions to form derivatives where Y
is other than H. Reaction of compounds of Formula I
. 35 in the presence of an acid acceptor with electrophilic~.
agents results in substitution on nitrogen. Strong - bases such as sodium hydride, potassium t-butoxide, potassium hydride, and other bases known in the art to :
.
' ~: .

- z ~

deprotonate amides are preferred in the process.
Suitable electrophiles include, but are not restricted to alkyl halides, acyl halides, acid anhydrides, carbonates, chloroformates, disulphides, and sulphenyl halides. This reaction is normally run in the the temperature range of 0-25C, but can be run at temperature up to 120C if unreactive electrophiles are used. Solvents not deprotonated under the ; reactions conditions such as tetrahydrofuran, dimethylformamide, dimetho~yethane, and diethyl ether are preferred.
Compounds of Formula I (X~O) can be converted to compounds of Formula I (X-S) by means of thiating agents. Conversion of amides to thioamides is well known in the art. Phosphorous pentasulfide either alone or in combination with organic or inorganic bases is a preferred reagent to effect this conversion. When phosphorous pentasulfide is used ; alone, organic bases such as pyridine are the preferred solvents. When it is used in conjunction with inorganic bases such as sodium bicarbonate, the preferred solvents are ethers such as diglyme.
25 Temperatures between 20 to 160C can be employed -- successfully with temperatures between 90 to 120C
preferred. These and other means to convert amides to thioamides are described by Lapucha, SYnthesis, 256 (1987).
The following Examples further illustrate the invention.

~- 35 .

.
:.

- - . . ~ , -., ., , . , ~ . . .

2~ . 4 '3 Example 1 3,3a,4,5-Tetrahydro-N-[4-(trifluoromethyl)phenyl]-2H-thieno r2,~-9l indazole-2-carboxamide _ Step A: 6,7-Dihydro-5-methylenebenzo[b]thiophen-4(SH)-one To 20.0 mL of tetramethyldiaminomethane was added 10.0 g of 6,7-dihydrobenzo[b~thiophen-4(5H~-one ; all at once. To this mixture was added 20.~ mL of acetic anhydride, dropwise. The reaction mixture exothermed to 45C and was heated to 122C for 15 minutes and then cooled to 90C where it was kept for 60 minutes. The dark solution was poured into cold water and extracted with ether. The ether was extract-ed with a saturated solution of NaHCO3 and then washed with brine. The ether layer was dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo .~;
to afford a yellow oil. The yellow oil was flash-chromatographed using 10% ethyl acetate and 90%
hexanes as eluent to afford 6.18 9 of a white solid, m.p. 47-49C. 200 MHzlH NMR(CDC13) ~ 2.97 ~t, 2H), 3.07 ~t, 2H), 5.46 (s, 1~), 6.17 (s,lH), 7.11 (d, lH), -i 7.98 (d, lH); I.R. ~Nujol) 1660 cm~l.
j'~

~i Step B: 3,3a,4,5-tetrahydro-2~-thieno[2,3-g]indazole ,,.
:i` 30 To 20 mL of anhydrous ethanol was added 1.2 g of the product from Step A and 0.40 9 of hydrazine hydrate. The reaction mixture was heated at reflux for 2 h, cooled, poured into cold water and e~tracted with ether. The ether extrzcts were washed with water and brine, dried over anhydrous magnesium sulfate, filtered and utilized without concentration or purification in Step C.

:: :

: . . - : , 2~

Step C:
Preparation of title compound was as follows.
To a 150 mL solution of the product from Step B in ether was added 1.50 9 of ~,a,a-trifluoro-p-tolyl-isocyanate. The reaction mi~ture was stirred at room temperature for 1 hr. where a precipitate was formed.
The reaction mixture was filtered and the precipitate was washed with ether to afford 0.20 g of a white solid, m.p. 219-221C. 200 MHzlH NMR(CDC13) ~ 1.98 (bm, lH~, 2.48 (bm, lH), 3.10 (m, 2H), 3.42 (m,2H1, 4.43 (m, lH), 7.25 (d, lH), 7.36 (d, lH), 7.56 (d,2H), 7.67 (d,2H), 8.18 (bs, lH); I.R. ~Nujol) 3370,1668 cm~ .
: ' ' E~ample 2 7-Chloro-3a,4,-dihydro-3a-phenyl-N-[4-(trifluoro-methyl)phenyl)-3H-pyrazolo[5,1-c][1,4] benzoxazine-2-carbo~amide Step A: 4-chloro-1-nitro-2-(phenyl-2-propenyloxy)-benzene . ~.
- 25 A solution of 5-chloro-2-nitrophenol (79) in dimethylformamide (40ml) was stirred at room temperature with l-bromo-2-phenyl-2-propene (8ml) and potassium carbonate (5.59) or 18h. The reaction mixture was diluted with water (200 ml) and e~tracted with ether (100 ml). The ether was washed with water (3 s 100 ml). The solvent was removed under reduced pressure and the residue was crystallized from he~anes. The Yellow solid (8.6 9) was the desired product. m.p. 74.5-75.5C
35 NMR (200MHz) CDC13; 6 7.8 (d,lH,ArH) 7.4-7.0 (m, 7H, ArH) 5.6 (S,S, 2H, CH2) 5.0 (S, 2H, CH2O).

- . , . - . : ,. . . .

2~ 13 '., ~
Step B: 4-chloro-2-[(2-phenyl-2-propenyl)oxy]-benzenamine The compound of Step A (7.2 9) was added to a suspension of tin (II) chloride (28 9) in ethanol (45 ml). The mixture was refluxed for l.5 h. The reaction was diluted with ethyl acetate and neutralized by careful addition of saturated sodium bicarbonate solution. The organic solution was washed with brine and the solvent was dried over magnesium sulfate.
Evaporation of the solution left a thick oil of the title compound (5.8 9).
~i 15 NMR (200MHz) CDCl3 ~ 7.4-6.6 (m, 8H, ArH) 5.6-5.4 (S,S, 2H, CH2) 4.9 (S, 2H, CH2O) 3.2 (~r, hH2) .; . .
Step C: methyl chloro 1[4-chloro-2-[(2-phenyl-2-propenyl)oxy]phenyl]hydrazono]acetate . .
Using the procedure of E~ample 4 (Step B), the compound of Step B (5.6 9) was converted to the title compound (2.8 9). The chromatography was carried out with hexanes/ethyl acetate (8:1); m.p. 88-90C.
NMR (200MHz) CDC13 ~ 8.6 (br- s, NH2) 7.3-6.9 (m, 8H, ArH) 5.7-5.6 (m, 2H, CH2) 4.9 (s, 2H, CH2O) ~ .
Step D: methyl 7-chloro-3a-~-dihydro-3a phenyl-; 3H-pyrazolo~5, l-c]tl,41benzoxazine-2-carboxylate : 35 The compound of Step C ~2.5 9) was dissolved in benzene (lO0 ml), treated with triethylamine (5 ml), and ., .
.
i' ' '~

~; i' .; '' ~"i .: .. .. ..

... -, . . . . . , .: , - .; , . ;. , ~ :
.. . ..

r~

heated at reflux for 24 h. The cooled mixture was diluted with eth~l acetate (100 ml) and lN HCl (100 ml). The organic layer was dried and evaporated. The residue was chromatographed on silica gel with hexane/ethyl acetate (5:1). The title compound (1 g) was a solid. m.p. 145-146C
NMR (200MHz) CDC13 ~ 7.6-6.8 (m, 8H, ArH) 4 . 65 (d, lH, CH) 3.9 (d, lH, CH) 3.8 (S, 3H, CH3) 3.4 (m, 2H, CH

Step E:
Preparation of title compound was as follows. The compound of Step D (1.0 9) was suspended in methanol (10 ml) and treated with 50% aqueous sodium hydroxide (1 ml) and heated to reflux for 10 min. The mixture was acidified and extracted with ethyl acetate. The dried organic extract was evaporated. The residue was dissolved in benzene (15 ml) and treated with thionyl chloride (1.5 ml). The mixture was heated to reflux for 2 h and then evaporated. The residue was dissolved in tetrahydrofuran ~20 ml) and one half was added to a solution of p-trifluoromethoxyaniline (0.4 9) and triethylamine (1.0 ml) in tetrahydro~uran (10 ml).
After stirring for 1 h the mixture was partitioned between ethyl acetate (50 ml) and lN HCl (50 ml).
The dried organic layer was evaporated.
Chromatography of the residue on silica gel in he~anes/ethyl acetate (7:1) gave the title compound ~0.39 9). m.p. 140-196C.
, ,:

:,,, : . , - ......... , ., , : ,, , , . . :: . : --- 2t~

NMR (200MHz) CDC13 ~ 8.6 (br, NH) 7.8-6.9 (m, 12H, ArH) 4.7 (d, lH, CH) ; 3.8 (d, lH, CH) ., .
3.4 (dd, 2H, CH2) , Example ~
Methyl 7-fluoro-3a,4-dihyrdO-2-[[i4-(trifluoromethyl)phenyl]amino~carbonyll-3H~pyrazolo[5, l-cl-rl!9lbe~ o~azine-3a-carbo:~Ylate .__ ,;
Step A: methyl 2-[(5-fluoro-2-nitrophenoxy) methyl]-2-propenoate ~,, - The compounds 5-fluoro-2-nitrophenol (8.0 g), methyl 2-bromomethylacrylate (9.5 g) and potassium carbonate (7 9) under the conditions of Example 2, ,~ 20 (Step A) gave the title compound (11.6 9). m.p.
` 89-92C
NMR (200MHz) CDC13 ~ 8.0 (m, lH, ArH) 6.9 ~m,2H, ArH) 6.4-6.2 (S,S, 2H, CH2) ;
4.8 (S, 2H, CH2O) 3.8 (S, 3H, CH30) ~; .;
Step B: methyl 2-1~2-amino-5-fluoropheno~y)-methyl]-2-propenoate The compound of Step A (11.~ 9~ was converted to the title compound (8 9) by the method of the E~ample 2 (Step B).
NMR (200MHz) CDC13 ~ 6.8 (m, 3H, ArH) 6.5 ~ 6.0 (S, S, 2H, CH2) 4.8 (S, 2H, CH2O) 4.2 ~Br, NH2) 3.8 (S, 3H, CH30) ..

;:

~, "~ ,'s, ~ '"~ " "

. - . ~ .. . .. : .
.

2~
.

5 Step C: methyl 2-[[2-[2-(1-chloro-2-methoxy-2-o~o-ethylidene)hydrazino]-5-fluorophenoxy]-methyl~-2-propenoate Using the procedure of Example 4 (Step C) the 10 title compound (2.1 9) was prepared from the compound of Step ~ (7.5 g).
NMR (200MHz) CDC13 ~ 8.7 (br. s, NH) 7.6 (m, lH, ArH) 6.9 (m, 2H, ArH) 6.5 (S, lH, CH2) 6.0 (S, lH, CH2) 4.8 (S, 2H, CH2) 3.8 (S, 6H, 20CH
. .
20 Step D:
Preparation of title compound (0.13 g) was as follows. The procedure of Example 2 (Steps D and E) .~ were used with the compound of Step C (1.8 9) and the p-trifluoromethoxyaniline was replaced with 25 p-trifluoromethyl-aniline. m.p. 177.5-181C.
NMR (200MHz) CDC13 ~ 8.6 (br, NH) 7.7-6.8 (m, 7H, ArH) 4.7 (d, lH, CH2O) ; 3.8 (S, 3H, CH30) 3.8-3.4 (m, 3H, CH2, CH2O) .
:
~

., :

.. , - . ~ . . , . .. , -~: 2~ 3 ..

Example 4 Methyl 3a,9-dihydro-3a-phenyl-3H-pyrazolo-r s . l-cl r 1 . 41benzothaazine-2-~arbo~y~ate-5-oxi ;, Step A: 2-t(2-phenyl-2-propenyl)thio]-benzenamine The compound, 2-aminothiophenol, (12.5 9) was added to a solution of sodium hydroxide (4.5 9) in ethanol (100 ml) keeping the temperature less than 30C. Then l-bromo-2-phenyl-2-propene (21 g) was added and the mi~ture was stirred at 60C for 3h. The precipitated solid was filtered and washed with ethanol. The solvent was removed and the residue was ' chromatographed on silica gel with hexanes/ethyl acetate (7:1) to yield the title compound (14.5 9).
As an oil.
20 NMR (200MHz) CDC13 ~ 7.3-7.0 (m, 9H, ArH) 5.3-5.0 (m, 2H, CH2) 4.0 (Br~ NH2) 3.8 (S, 2H, CH2S) . .
Step B: methyl chloro[t2-1(2-phenyl-2-propenyl)-~' thio]-phenyl]hydrazono]acetate ,......................................................................... .
The compound of Step A (14.5 9) was treated with 6N HCl (22 ml) and water (100 ml?. This mi~ture 30 was cooled to below 0C and treated dropwise with an -aqueous solution of sodium nitrite (4.2 9). The resulting mi~ture was decanted into an insulated dropping funnel. The mi~ture was added to a cooled (-S to-10C) mi~ture of sodium acetate (15 9) and methyl 2-chloroacetoacetate (5 ml) in ethanol (100 ml) so that the internal temperature did not exceed 5C.

.

, . .

2~ .4 3 The mi~ture was allowed to come to room temperature over 2 h and then e~tracted with ether. The dried organic layer was evaporated and chromatographed on silica gel with ether/hexanPs (1:2). The title compound (11.5 9) was isolated as a yellow oil.
NMR (200MHz) CDC13 ~ 9.4 (br, NH) 7.5-7.0 (m, 9H, ArH) 5.2 (S, lH, CH2) 4.8 (S, lH, CH2) 3.9 (S, 3H, CH3) 3.8 (S, 2H, CH2S) Step C: methyl chloro[,~2-[(2-phenyl-2-propenyl)-~- sulfinyl]phenyl]-hydrazono]acetate The compound of Step B (5 9) was stirred with occasional warming in acetic acid (45 ml) and treated with 30% aqueous hydrogen peroxide (2.0 ml). After stirring for 5 h, water (200 ml) was added and the . .
P.h. was adjusted to 6 with sodium bicarbonate.
Saturated sodium bisulfite solution (3 ml) was added and the mi~ture was e~tracted with dichloromethane (200 ml). The organic layer was dried and evaporated ` to give the title compound (4.9 g). -NMR (200MHz) CDC13 6 7.6-7.0 (m, 9H, ArH) 5.6-4.2 tm, 4H, CH2) - 4.0 (S, 3H, CH30) Step D:
Preparation of title compound (1.0 9) was as follows. The method of E~ample 2 (Step D) was applied to the compound of Esample 12 (4.5 9).
Purification was accomplished by chromatography on ; silica gel with he~anes~ethyl acetate (1:1). ~!
:, .

, . . .--. ., : - . .. . ... . -. ;., .. , . .... . ,,-,~ . , .. . - . , .. - -. . ....

.' ' . " " ' . '' ' ' ' ' ' . " '. ' " ': ' ' ' ` ' ' . . ',, . ' '. ' " ;
~ ' , ' . ' ' ' ' , ' .: ' ' . .~ '' ' ' - ., : :' `' . '' ' , / ' ~ . , ',' . j " ' ' ' ' , ' ' ~ , ' ~ . ' ' ~. 44 ~
., ~
~ NRM (200MHz) CDC13 o 7.8-7.0 (m, 9H, ArH) ; 4.2 (dd, lH, CH2) 3.9 (S, CH30, 3H) 3.6 (m, 3H, CH2) :
Example 5 3a,4-Dihydro-3a-phenyl-N-t4-(trifluoromethyl)phenyl]-3~-pyraz~lç~hl~rlbenzothia~in~-2-c A rbo~amide __ The compound of Example 4 (Step D) (1 9) was treated with Z0% aqueous titanium (III) chloride (2 ~ ml) in dichloromethane (20 ml) and methanol (20 ml).
: 15 The mi~ture was stirred for 20 min. at room temperature and partitioned between ethyl acetate -(150 ml) and water (200 ml). The dried organic phase ; was concentrated and the residue was subjected to the conditions of E~ample 10 with p-trifluoromethyl-aniline in place of p-trifluoromethoxyaniline. The title compound (0.6 9) was isolated as a solid. m.p.
238-240C.
~ NMR (200MHz) CDC13 ~ 8.6 (br, NH) ;2 7.8-6.9 (m, 13H, ArH) ; 25 3.6 (S, 2H, CH2) 3.4 (S, 2H, CH2) By the general procedures described herein, or ob~ious modifications thereof, the compounds of !' Tables 1 through 16 can be prepared.

., .
., .
,........................................................................... .

., .',j ' .

2~3i~, .~ 3 SUMMARY OF TABLES
Table Q Y G

1 Q-l H

. 3 Q-3 H

^: 6 Q-6 H S

:` 8 Q-5 H O

` 10 Q-7 H O
,:

`: :
20Table 11 Ra is H, X is O, G is S
Table 12 Ra is H, X is 0, G is S, Y is S-J
-. Table 13 Q is Q-8, Ra is H, Y is H, A is CH2 Table 14 Q is Q-8, Ra is ~, Y is H
Table 15 Q is Q-8, Ra is H -~' 25 Table 16 Q is Q-8, Y is H

In the Tables that follow, the values of Q will ,.
. be referred to by the following numbering system:
~:
.

:.
~ ~:

.~, ' .
. .

., ,~ ., , '. . ~ '',, , ' .. , , ' ' ,'. . ;.'.' ' ' ' ~`'` '.i J ~ 3 '~ 5 ~ 5 ~o 1 o N--? N--N

:,' , 2 2 5~ 5 ~ ;~

`~ 1 2 1 2 : -., ~f Q- '3 Q_ 4 .~ 2~
~ ~ .

. :
.: .

5~ 6 ~. 1 2 1 2 :-` 35 ~ A ' . . ~ .

.',' ~.

" , . ' ' ': ' Z~ 43 10 !5 ~1 Q-7 s?-e :~ 15 ,7~ ~'. ' ,, ' ` , ", , ,:

. - 25 ?, .
,,,, :.
: :' , , .
~" ' /'.~ 30 .~ ~:

i, :
.
;`
i 35 . ::
i .

., : .. .

2~r3~ Q3 Table 1 Rl R2 A B X Ral, Ra2 ', .
.. 4-CF3 2 H,H
4-Cl HCH2 HO H,H
4-Br 2 H,H
4-CF3 5-C12 H,H
4-C1 5-ClCH2 HO H,H ~;
,~ 4-Br 5-ClCH HO H H
2 ~ .
4-CF3 5-F 2 H,H
: 4-C1 5-FCH2 H O H,H
4-Br 5-FCH2 H O H,H
4-CF3 5-CN2 H,H
;j 4-C1 5-CNCH2 HO H,H
4-Br 5-CNCH2 HO H,H
2 4-CF3 5-BrCH2 HO H,H -,'. 4-C1 5-Br CH2 H O H,H
,., 4-Br 5-Br CH2 H O H,H
, 4-CF3 5-Me 2 H,H
~ 25 4-C1 5-Me CH2 H H,H
:~ ~-Br 5-Me CH2 H O H,H
4-CF3 7-F CH2 H O H,B
4-C1 7-F CH2 H O H,H
4-Br 7-F CH2 H O H,H
4-CF3 2 2 H,H
' 4-C1 2 2 H,H ~-4-Br 5-NMe2 CH2 H H,H
4-CF3 5-CF3 2 H,H
4-C1 5-CF3 2 R,H
4-Br 5-CF3 2 H,H
4-CF3 2 H,H

:
,~ .

' ' - . ~ :: ': - ,. ': ': ' . . ..

2~ 3r~

. R2 A BX Ral, Ra2 : 5 4-Cl H CH2Me O H,H
4-Br H CH2Me 0 H,H
4-CF3 5-Cl CH2Me O H,H
4-C1 5-Cl CH2Me O H,H
4-Br 5-Cl CH2Me O H,H
4-CF3 5-CF3 CH2 Me O H,H
4-C1 5-CF3 CH2 Me O H,H
4-Br 5-CF3 CH2 Me O H,H
~- 4-CF3 H CH2Et O H,H
4-Cl H CH2Et O H,H
4-Br H CH2Et O H,H
4-CF3 5-F CH2Et O H,H
4-C1 5-F CH2Et 0 H,H
~, 4-Br 5-F CH2Et O H,H
4-CF3 Et O H,H
~ 4-C1 5-CN CH2Et O H,H
.',l 4-Br 5-CN CH2Et O H,H
~` 4-CF3 H CH2allylO H,H
4-Cl H CH2allylO H,H
4-Br H CH2allylO H,H
.. 4-CF3 S-Br CH2allylO H,H
4-C1 5-Br CH2allylO H,H
- 4-Br 5-Br CH2allylO H,H
n 4-CF3 5-Cl C~2allylO H,H
; 30 S-Cl CH2allylO H,H
4-Br 5-Cl CH2allylO H,H
4-CF3 H CH2 2 H,H
- 4-Cl H CH2CO2Me H,H
;, 4-Br H CH2 2 H,H

,. 4-CF3 S-F CH2 2 H,H
4-C1 5-F CH2 2 H,H

,' ' ,"
, ... .
-... : .. :.. : . .. .. . . - . , . ., . .. :. " .,: . :. , .: . , , . : ~ ,: :
.,. , .... , .. .. , . ... , . . . .. : - .. :. .. " , .: - . : .: .

-" 2~

1 2 A B X Ral, Ra2 4-8r 5-F CH2 2 H,H
4-CF3 5-Cl CH2 2 H,H
4-C1 5-Cl CH2 2 H,H
4-Br 5-Cl CH2 2 H,H
4-CF3 5-Br CH2 2 H,H
4-C1 5-Br CH2 2 H,H
4-8r 5-Br CH2 2 H,~
4-CF3 5-CN CH2 2 H,H
4-C1 5-CN CH2 2 H,H
4-Br 5-CN CH2 2 H,H
4-CF3 5-CF3 CH2 2 H,H
4-C1 5-CF3 CH2 2 H,H
4-Br 5-CF3 CH2 2 H,H
. 4-CF3 5-Me CH2 2 H,H
`. 20 4-C1 5-Me CH2 2 H,H
, 4-i3r 5-Me CH2 2 H,H
4-CF3 H CH2 2 H,H
' 4-Cl H CH2 2 H,H
, 4-Br H CH2 2 H,H
4-CF3 5-Cl CH2 2 H,H
4-C1 5-Cl CH2 2 H,H
4-Br S-Cl CH2 2 H,H
4-CF3 H CH2 CO2-i-Pr O H,H
4-CI ~ CH2 CO2i-Pr O H,H
4-~3r H CH2 CO2i-Pr O H,H
4-CF3 H CH2 2 2 3 H,H
4-Cl H CH2 2 2 3 H,H
4-Br H CH2 2 2 3 H,H
4-CF3 H CH2 CO2allyl 0 H,H
4-Cl H CH2 CO2allyl H,H

.

:, :
R2 .A B X Ra ~ Ra2 M
; 4-Br H CH2 C02allyl 0 H,H
4-CF3 H CH2 2 2 2 H,H
4-Cl H CH2 2 2 2 H,H
4-9r H CH2 2 2 2 H, H
4-CF3 H CH2 Ph O H,H
~ 4-Cl H CH2 Ph O H,H
- 4-Br H CH2 Ph O H,H -. 4-CF3 5-Cl CH2 Ph O H,H
4-C1 5-Cl CH Ph O H H
. 2 ' :.
4-Br 5-Cl CH2 Ph O H,H
4-CF3 H CH2 4-Cl-Ph O H,H
- 4-Cl H CH2 4-Cl-Ph O H,H
~;~ 4-Br H CH2 4-Cl-Ph O H,H
.. 4-CF3 5-CF3 CH2 4-Cl-Ph O H,H
ti- 20 4-C1 5-CF3 CH2 4-Cl-Ph O H,H
4-Br 5-CF3 CH2 4-Cl-Ph o H,H
., 4-CF3 H CH2 4-F-Ph O H,H
4-Cl H CH2 4-F-Ph O H,H
4-Br H CH2 4-F-Ph O H,H
` 25 4-CF3 H CH2 H O Me,H ~ ~'i . 4-Cl H CH2 H O Me,H
i 4-Br H CH2 H O Me,H .c i 4-CF3 5-Cl CH H O Me,Me `
4-C1 5-Cl CH2 H O Me,Me ~ 30 4-Br 5-Cl CH2 H O Me,Me :. 4-CF3 H CH2 H S ~,H .,:
A 4-CI H CH2 X S H,H
' 4-Br H CH2 H S H"H

. . .
4-CF3 H CH2 Me S H,H
4-Cl H CH2 Me S H,H
4-Br H CH2 Me S H,H
. 4-CF3 H CH2 COzMe S H,H
'' :
' ' .

~ "
.~ .
., .

2. r~ a~

1 R2 A B X Ral, Ra2 4-Cl H CH2 C02Me S H,H
-~ 4-Br H CH2 C02Me S H, H
: 4-CF3 5-Cl CH2 H S H,H :, . 4-C1 5-Cl CH2 H S H,H
4-Br 5-Cl CH2 H S H,H
. 4-CF3 5-Cl CH2 Me S H,H
; 4-C1 5-Cl CH2 Me S H,H
4-Br S-Cl CH Me S H,H
:- 2 ;: 4-CF S-Cl CH CO2Me S H,H
?~ 15 4-C13 5-Cl CH2 C2Me S H,H
: Br 5-Cl CH2 C02Me S H,H
4-CF3 5-Me 2 S H,H
4-C1 5-Me CH2 H S H,H
: 4-Br 5-Me CH2 H S H,H
;~ 4-CF3 H O H O H,H
4-Cl H O H O H,H
4-8r H O H O H,H
, 4-CF3 5-Cl O H O H,H
. 4-C1 5-Cl O H O H,H
:;', 25 4-Br 5-Cl O H O H,H
.~. 4-CF3 5-Br O H O H,H
4-C15-Br , O H O H,H
4-Br:5-Br O H O H,H
, 4-CF35-CF3 0 H O H,H
5-CF3 0 H O H,H
` 4-BrS-CF3 0 ~ O H,~
~ 4-CF3 H O Me O H,H
- 4-Cl H O Me O H,H

Ç. 4-8r H O Me O H,H
4 CF3 5-Cl O Me O H,H

':

.', ' "' .

1 R2 A B X Ral, Ra2 : -4-C1 5-Cl O Me O H,H
4-Br 5-Cl O Me O H,H
4-CF3 5-Br O Me O H,H
4-C1 5-Br O Me O H,H
` 10 4-Br 5-Br O Me O H,H
.~. 4-CF3 5-CF3 O Me O H,H
4-C1 5-CF3 O Me O H,H
4-Br 5-CF3 O Me O H,H
~:~ 4-CF3 5-F O Me O H,H
:~ 15 4-C1 5-F O Me O H,H
:~ 4-Br 5-F O Me O H,H
`~ 4-CF3 H OC2M~ H,H
.- 4-Cl H OCO2Me O H,H
: 4-Cl H OCO2Me H,H
` 20 4-Br H 2 H,H
. ~ :
4-CF3 5-C1 2 H,H
' 4-C1 5-ClO CO2Me O H,H
4-Br 5-ClO CO2Me O H,H
4-CF3 H O Ph O H,H
4-Cl H. O Ph O H,H
4-Br H O Ph O H,H
. 4-CF3 S-BrO Ph O H,H
4-C1 5-BrO Ph O H,H
4-Br 5-BrO Ph O H,H
4-cr3 H O H O Me,Me ,, 4-Cl H O H O Me,Me 4-~r H O H O Me,Me 4-CF3 H H O H,Me :.
- 4-Cl H O H O H,Me : 4-Br H O H O H,Me ~.
:' ;

2 ~ ;L iA~

: 54 5 Rl - R2 A B X Ral, Ra2 4-CF3 H O HO H,Ph 4-Cl H O HO H,Ph 4-Br N O HO H,Ph 4-CF3 H O HO H,CO2Me 4-Cl H O H O H,CO2Me 4-Br H O H O H,CO2Me 4-CF H O H S H,H
4-Cl H O H S H,H
. 4-Br H O H S H,H
4-CF3 H S H O H,H
4-Cl H S H O H,H
4-Br H S H O H,H
. 4-CF3 S-Cl S H O H,H
4-C1 5-Cl S H. O H,H
4-8r 5-Cl S H O H,H
4-CF3 5-Br S H o H,H
4-C1 5-Br S H O H,H
4-Br S-Br S H O H,H
4-CF3 5-CF3 S X O H,H -.1 4-C1 5-CF3 S H O H,H
~' 25 4-Br 5-CF3 S H O H,H
-" 4-CF3 H S Me O H,H
.' 4-Cl H S Me O H,H
':' 4-Br H S Me O H,H ::
,: :
4-CF3 5-Cl S Me O H,H
4-C1 5-Cl S Me O H,H
4-Br 5-Cl S Me O H,H ~
4-CF3 5-Br S Me O H,H ::-: 4-C1 5-Br S Me O H,H
.
4-Br 5-Br S Me O H,H ~ :
4-CF3 5-CF3 S Me O H,H
;- 4-C1 5-CF3 S Me O H,H
4-Br 5-CF3 S Me O H,H

~ ,~

'~ Z~ L~1.9 ;

1 R2 A B X Ral, Ra2 4-CF3 5-F S Me O H,H
4-C1 5-F S Me O H,H
. 4-Br 5-F S Me O ~,H j ~
4-CF3 H S CO2Me H,H ~
- 10 4-Cl H S CO2Me H,H
4-Br H S 2 H,H
4-CF3 5-C1 2 H,H
. 4-C1 5-Cl S CO2Me O H,H ..
; 4-Br 5-Cl SCO2Me O H,H
4-CF3 H S Ph O H,H -4-Cl H S Ph O H,H
4-Br H S Ph O H,H
4-CF3 5-Br S Ph O H,H
; 4-C1 5-Br S Ph O H,H
; 20 4-Br 5-Br S Ph O H,H
4-CF3 H S H O Me,Me ~.~ 4-Cl H S H O Me,Me ,,; 4-Br H S H O Me,Me ~1 4-CF3 H S H O H,Me ~, 25 4-Cl H S H O H,Me ~.
.. , 4-Br H S H O H,Me q-CF3 H S H O H,Ph j 4-Cl h S H O H,Ph ' 4-8r H S H O H,Ph ~ q-CF3 H S H O H,CO2Me . :
` 30 H S H O H,CO2Me ::
., 4-Br H S H O H,CO2Me . -4-CF3 H S H S H,H
, 4-Cl H S ~ S H,H

i 4-Br H S H S H,H
,. 35 4-SMe H CH2 2 H,H ;
$ 4-SO2Me H CH2 CO2Me H,H
A 2 2 H C82 2 H,H
:', .

., .
::
~-~
.~ .

2~ .9 Rl R2 A 8X R 1, R 2 a a 4-CF2Cl H CH2 CO2Me H,H
4-CO2Me H CH2 CO2Me H,H
4-CO2CF3 ~ CH2 ~2Me H,H
~ 4-F H CH2 CO2Me H,H
:~ 10 4-CN H CH2 CO2Me H,H
4-Me ~ CH2 CO2Me H,H
3,4-CH2C(Me)201H CH2 CO2Me H,H
3,4-CF2CF202 H CH2 CO2Me H,H
4-CF3, 3-Cl H CH2 2 H,H
4-I H CH2 CO2MeO H,H
4-OMe H CH2 CO2Me H,H
4-0-t-Bu H CH2 CO2Me H,H
,~. 4-t-Bu H CH2 CO2Me H,H
.~ 4-CF3 H CH2 2 H,~ :
4-CF3 H CH2 CONH2O H,H
4-cr3 H CH2 CONHMe O H,H
: 4-CF3 H CH2 CONMe2 O H H
4-CF3 H CH2 CO2CH2Ph O H H
~; 4-CF3 H CH2 CH2Ph O H,H
4-CF3 2 O H,H ::
4-CF3 2 O H,H

4-CF3 H CH2 CNzOCH3 O H,H
4-CF3 H CH2 CH2C2Me H,H
. 30 3 H CH2 CH2CH2CN O H,H

iq~At:e- Ph(ll~

2. designate~ Ph(Rl) a6 ~ F

F F ~ :
.. . ..
.
' j' ", ,.: ~ . : - , . - , , .. . , .. : ... ... . . .. . .

Z~3~3~i~43 Table 2 -Rl R2 A B X Ral, Ra2 .
4-CF3 H CH2 H- O H,H
4-Cl H CH2 H O H,H
: 4-Br H CH2 H O H,H
4-CF3 4-F CH2 H O H,H
4-C1 4-F CH2 H O H,H
4-Br 4-F CH2 H O H,H
4-CF3 4-Cl CH2 ~ H,H
4-C1 4-Cl CH2 H O H,H
4-Br 4-Cl CH2 H O H,H
4-CF3 4-Me CH2 H O H,H
4-C1 4-Me CH2 H O H,H
4-Br 4-Me 2 H,H
. 4-CF3 4-OMe CK2 H O H,H .
4-C1 4-OMe CH2 H O H,H , 4-Br 4-OMe CH2 H O H,H , '!:' 4-CF3 4-Br 2 H,H
~ 4-C1 4-Br CH H O H,H
.: 2 :
~, 4-Br 4-Br CH2 H O H,H
4-CF3 6-F CH2 H O H,H
4-C1 6-F CH2 H O H,H
~' 4-Br 6-F CH2 H O H,H
'~! 4-CF3 6-Cl CH2 H O H,H
~. . 4-C1 6-Cl CH2 H O H,H
,~. 4-Br 6-Cl CH2 H O H,H
~-CF3 7-F CH2 H O ~,H :
` 4-C1 7-F CH2 H ~,H ::~
:i 4-~r 7-F CH2 8 O H,H
4-CF3 H CH2 Me O H,H

H CH2 Me O H,H

:~ .

., .
,. .

2~ 4~

: 58 .

. 5 Rl R2 A BX Ral, Ra2 : 4-Br H CH2 MeO H,H
4-CF 4-F CH2 CH3O H,H
4-C1 4-F CH2 CH3O H,H
4-Br 4-F CH2 CH3O H,H
,~ 10 4-CF3 4-C1 CH2 CH3O H,H
4-C1 4-Cl CH2 CH3O H,H
4-Br 4-C1 2 3 H,H
4-CF3 H CH2 Et H,H
; 4-Cl H CH2 Et H,H
~ 15 4-Br H CH2 Et H,H
.~ 4-CF3 4-F CH2 Et H,H
4-C1 4-F CH2 EtO H,H
4-Br 4-F CH2 EtO H,H
`: 4-CF3 4-Cl CH2 EtO H,H
; 20 4-C1 4-C1 2 O H,H
4-Br 4-Cl CH2 CN2O H,H
4-CF3 H CH2 allylO H,H
4-Cl H CH2 allylO H,H
- 4-Br H CH2 allylO H,H
. 25 4-CF3 4-F CH2 allylO H,H
4-C1 4-F CH2 ~llylO H,H
4-Br 4-F CH2 allyl O H,H
.~ 4-CF3 4-Cl CH2 allylo H,~

4-C1 4-Cl CH2 allyl O H,H
4-Br 4-Cl CH2 allylO H,H
4-CF3 H CH2 CO2MeO H,H
v 4-Cl H CH2 CO2MeO H,H
4-Br H CH2 2 R,H
4-CF3 4-F CH2 CO2Me H,H
4-C1 4-F CH2 CO2MeO H,H
4-Br 4-~ CH2 CO2Me O H,H

... .
-, -.

2 ~ 3 Rl R2 A BX Ral, Ra2 ~
4-CF3 4-Cl C~2 CO2Me H,H
4-C1 4-Cl CH2 CO2Me H,H
;~ 4-Br 4-Cl CH2 CO2Me H,H
4-CF3 4-CN C~2 2 H,H
4-C1 4-CN CH2 CO2Me H,H
. 4-8r 4-CN CH2 CO2Me H,H
': 4-CF3 4-Br CH2 2 H,H
4-C1 4-Br CH2 2 H,H
4-Br 4-Br CH2 2 H,H
4-CF3 4-CF3 CH2 CO2Me H,H
.~ 4-C1 4-CF3 C~2 CO2Me H,H
4-Br 4-CF3 CH2 2 H,H
'~ 4-CF3 4-Me C~2 2 H,H
i,. 4-C1 4-Me .CH2 CO2Me H,H
4-Br 4-Me CH2 2 H,H
4-CF3 H CH2 CO2Et H,H
4-Cl H CH2 CO2Et H,H
i 4-Br H CH2 CO2Et H,H
,, 4-CF3 4-F CH2 CO2Et H,H
4-C1 4-F CH2 CO2Et H,H
. 4-Br 4-F CH2 CO2Et H,B
.. 4-CF3 H CH2 CO2-i-PrO H,H
~: . 4-Cl ~ C~2 CO2-i-PrO H,H
4-Br 2 2 H,H
3 2 2 2 3 H,H
4-C1 H 2 2 2 3 H,H
. 4-Br H CH2 C2CH2CF3O H,H
., 4-CF3 H CH2 CO2~11ylO H,H

- 4-Cl H CH2 CO2nllylO H,H
- 35 H CH2 CO2allyl H,H
.~ 4-CF3 H CH2 C2CH2CH2C1 H,H
; 4-Cl H CH2 C2CH2CH2C1 H,H

.~

,;

2~3$ ~

Rl R2 A B X Ral, Ra2 _ _ .
4-Br H CH2 C2CH2CH2C1 H,H
4-CF3 2 O H,H
4-C1 2 O H~H
4-8r HCH2 Ph O H,H
4-CF3 4-FCH2 Ph o H,H
4-C1 4-FCH2 Ph O H,H
: 4-Br 4-FCH2 Ph O H,H
.. 15 4-CF3 H CH2 4-Cl-Ph O H,H
4-Cl HCH2 4-Cl-Ph O H,H
4-Br HCH2 4-Cl-Ph O H,H
4-CF 4-FCH2 4-Cl-Ph O H,H
4-C1 4-FCH2 4-Cl-Ph O H,H
; 20 4-Br 4-FCH2 4-Cl-Ph O H,H
4-CF HCH2 4-F-Ph O H,H
. 4-Cl HCH2 4-F-Ph O H,H
4-Br HCH2 4-F-Ph O H,H
; 4-CF 2 O H,Me 4-C1 2 O H,Me 4-Br 2 O H,Me 4-CF3 HCH~ H O Me,Me :
4-C1 2 O Me,Me ,;
- 4-Br 2 O Me,Me 4-CF HCH2 R S H,H
4-Cl HCH2 H S H,H
4-Br HCH2 H S H,H
4-CF3 HCH2 Me S ~,H
4-Cl HCH2 Me S H,H
4-Br ~2 Me S H,H

4-CF3 HCH2 CO2Me S H,H
. 4-Cl HCH2 CO2Me S H,H
4-Br HCH2 CO2Me S H,H

.'' ' '',",.
, ' "' .
..

:: .. . : : :~ . : . :. , : , , ~ . - ::: . : . .

2 ~ 4- ~

.
'~' , ~", ',"'.
1 R2 A B X Ral, Ra2 4-CF3 HCH2 H S H,H
4-Cl HCH2 H S H,H
4-Br HCH2 H S H,H
4-CF3 4-FCH2 Me S H,H
~ 0 4 Cl 4-F 2 5 H,H
!" 4-Br 4-F 2 S H,H
4-CF3 4-F CH2 C2Me S H,H
~ 4-C1 4-F CH2 C2Me S H,H
'~ 4-Br 4-F CH2 CO2Me S H,H
: 15 4-CF3 4-FCH2 H S H,H
4-C1 4-FCH2 H S H,H
~ 4-Br 4-FCH2 H S H,H
4-CF3 H O H O H,H .
4-Cl H O H O H,H :.
~; 20 4-Br H O H O H,H
4-CF3 4-F O H O H,H
4-C1 4-F O H O X,H
;~ 4-Br 4-F O H O H,H
.. , 4-CF3 4-Cl O H O H,H :
. 25 4-C1 4-Cl O H O H,H
::, 4-Br 4-Cl O H O H,H
~ 4-CF 4-Me O H O H H
:.~ 3 . 4-C1 4-Me O H O H,H
-~ 4-Br 4-Me O H O H,H
H O Me O H,H
.: 4-Cl H O Me O H,H
4-8r H O Me O ~,~
~i. 4-CF3 4-F O Me O H,~
`, 4-C1 4-F O Me O H,H
:, ,:
4-Br 4-F O Me O H,H .
4-CF3 4-Cl O Me O H,H
", " ' ,~ '.
,, .
.. .

, ~ , - : . : . , , : . , ' : . . ' ', '. :,: , .: : ' : , - 2r~ 4~

1 R2 A B X Ral, Ra2 .. . .
4-C1 4-Cl O Me O H,H
4-Br 4-Cl O Me O H,8 4-CF3 4-Me O Me o H,H
4-C1 4-Me O Me o H,H
4-Br 4-Me O Me O H,H
4-CF3 4-CF3 O Me H,H
4-C1 4-CF3 0 Me O H,H
4-Br 4-CF3 O Me O H,H
4-CF3 H O C02Me H,H
4-Cl H 0 C02Me H,H
4-Br H 0 C02Me 0 H,H
4-CF3 4-F 0 C0zMe O H,H
4-C1 4-F O CO2Me O H,H
4-Br 4-F O CO2Me O H,H
:~ 20 4-CF3 H O Ph H,H
4-Cl H O Ph O H,H :
4-Br H O Ph O H,H
'` 4-CF3 4-F O Ph O H,H
4-C1 4-F O Ph O H,H
. 25 4:Br 4-F O Ph O H,H
.. 4-CF3 H O H O Me,Me 4-Cl H 0 H 0 Me,Me 4-Br H 0 H 0 Me,Me ,~ 4-CF3 H O H O H,Me 4-Cl H O H O H,Me ~: 4-Br H O H O H,Me 4-CF3 H 0 H O H,Ph 4-Cl H O H 0 H,Ph -4-Br H O H O H,Ph . 4-CF3 H O H O H,CO2Me : 3S 4-Cl H O H O H,CO2Me ' ; 4-Br H O H O H,CO2Me 4-CF3 H O H S H,H ~

!~ ;

,' ' ` " " , ' ', '' ' . ' '' . . .' . ", . . ' ' . `' ' '. ' , ~ . " ' . ~ `

' ' / " . .' ' ' " ' ': ",. ' ` .. .~ ', ' ' ' ` ` , ,' . ` ' " ' ~. ' '`.' "

-` 2~

~ '.
.
S Rl R2 A B X Ral, Ra2 4-Cl H O H S H,H :-4-Br H O H S B,H
4-CF3 H S H O H,H
4-Cl 8 S H O H,H
4-Br H S H O H,H
4-CF3 4-F S H O H,H
4-Cl 4-F S H O H,H
4-Br 4-F S H O H,H
, 4-CF3 4-Cl S H O H,H
4-Cl 4-Cl S H O H,H
,:
4-Br 4-Cl S H O H,H
. 4-CF3 4-Me S H O H,H
: 4-Cl 4-Me S H O H,H
::
. 4-Br 4-Me S H O H,H
S 20 4-CF3 H S Me O H,H
, 4-Cl H S Me O H,H
4-Br H S Me O H,H
4-CF3 4-F S Me b H,H
4-Cl 4-F S Me O H,H
, 4-Br 4-F S Me O H,H
.-~ 4-CF3 4-Cl S Me O H,H
~ 4-Cl 4-Cl S Me O H,H
.' 4-Br 4-Cl S Me O H,H
-j! ' 4-Cr3 4-Me S Me O H,H
; 30 q-Cl 4-Me S Me O H,H
4-Br 4-Me S Me O H,H
4-CF3 6-F S Me O H,H
.- 4-Cl 6-F S Me O H,H

4-9r 6-F S Me O H,H
, 35 4-CF3 ~ 2 H,H
4-Cl H S CO2Me O H,H
4-Br H S CO2Me O H,H
~s,, 4-CF3 4-F 2 H,H

. ~ .

, :

: ~ : . , . : ~ . ;
- '. . : : , ~ , '' , -:: . :

~ 2~31",~ 4~) 1 2 _ X Ral, Ra2 4-C1 4-F S CO2Me O H,H
4-Br 4-F S CO2Me O H,H
4-CF3 4-Cl S Ph O H,H
4-C1 4-Cl S Ph O H,H
4-Br 4-Cl S Ph O H,H
: 4-CF3 H S Ph O H,H
: 4-Cl H S Ph O H,H
4-Br H S Ph O H,H
:~ 4-CF3 H S H O Me,Me 4-Cl H S H O Me,Me 4-Br H S H O Me,Me 4-CF3 H S H O H,Me 4-Cl H S H O H Me , 4-Br H S H O H Me -~ 4-CF3 H S H O H,Ph 4-Cl H S H O H,Ph ' . . 4-Br H S H O H,Ph 4-CF3 H S H O H,CO2Me 4-Cl H S H O H,CO2Me 4-i3r H S H O H,CO2Me ; 25 4-CF3 H S H S H,H
4-Cl H S H S H,H
4-~r H S H S H,H

... .:
`~ 30 . . .

~', : :
~

''~

-~` 2~6~$ 4'3 : 65 Table 3 S
Rl R2 AB X R 1 4-CF3 H CH2H O H,H
4-Cl H CH2H O H,H
4-8r H CH2H O H,H
4-CF3 5-Cl CH2H O H,H
.- 4-Cl 5-Cl CH2H O H,H
4-Br 5-Cl CH2H O H,H
4-CF3 5-F CH2H O H,H
`~ 15 4-Cl 5-F CH2H O H,H
.. 4-Br 5-F CH2H O H,H
.~ 4-CF3 5_CN CH2H O H,H
4-Cl 5-CN CH2H O H,H
4-Br 5-CN , 2 H,H
~''e 20 4-CF3 5-Br CH2H O H,H
i1 4-Cl 5-Br 2 H,H
~,, g-Br S-Br CH2H O H,H
,: 4-CF3 5-Me CH2H O H,H
.'. 4-Cl S-Me CH2H O H,H
: 25 4-Br 5-Me C~2H O H,H
.,, 4-CF3 7-F CH2H O H,H
;- 4-Cl 7_F CH2H O H,~
.-~ 4-Br 7-F 2 H,H
.~ 4-CF3 5-NMe2CH2H O H,H
4-Cl 5-NMe2CH2H O H,H
! 4-Br S-NMe2 2 j, H
; 4-CF3 5-CF3 CH2H O H,H
4-C1 5-CF3 CH2H O H,H
.. :

, .' ., .

,, .

' ' . :

2~3-~

R2 A B X Ral, Ra2 4-8r 5-CF3 CH2 H O H,H
4-CF3 2 O H,H
4-C1 2 O H,H
4-Br 2 O H,H
4-CF3 5-ClCH2 Me O H,H
4-C1 5-ClCH2 Me O H,H
4-Br 5-ClCH2 Me O H,H
4-CF3 5-CF3 CH2 Me O H,H
: 4-C1 5-CF3 CH2 Me O H,H
4-Br 5-CF3 CH2 Me o H,H
4-CF3 2 H,H
4-C1 H CH2 Et O H,H
4-Br H CH Et O H,H
. 2 . 4-CF3 5-F CH2 Et O H,H
'~ 20 4-C1 5-F CH2 Et H,H
4-Br 5-F CHz ~t O H,H
. 4-CF3 5-CN CH2 Et O H,H
.~' 4-C1 5-CN CH2 Et O H,H
.. ` 4-Br 5-CN CH2 Et O H,H
' 25 4-CF3 H CH2 allyl O H,H
4-Cl H CH2 allyl O ~,H
;~. 4-Br H CH2 allyl O H,H
4-CF3 5-Br CH2 allyl O H,H
4-C1 5-Br CH2 allyl O H,H
4-Br 5-Br CH2 allyl O H,H
~ ~ .

, . :

} 35 -. A .

." .

2~ 9 Rl R2 . A B X Ral, Ra2 4-CF3 5-Cl CH2allylO H,H
4-Cl S-Cl CH2allylO H,H
4-Br 5-Cl CH2allylO H,H
4-CF3 H CH2 2 H,H
4-Cl H CH2 2 H,H
4-Br H CH2C02Me O H,~ '~
4-CF3 5-F CH2 2 H,H
4-C1 5-F CH2 2 H,H
4-Br 5-F CH2 2 H,H
4-CF3 5-Cl CH2 2 H,H
4-C1 5-Cl CH2 2 H,H
4-Br 5-Cl CH2 2 H,H
4-CF3 5-Br ~H2 2 H,H
4-C1 5-Br CH2 2 H,H
4-Br 5-Br CH2 2 H,H
4-CF3 5-CN CH2 2 H,H
4-C1 5-CN CH2 2 H,H
4-Br 5-CN CH2 2 H,H
4-CF3 5-CF3 CH2 2 H,H
4-C1 5-CF3 CH2 2 H,H
4-Br 5-CF3 CH2 2 H,H
4-CF3 5-Me CH2 2 H,H
4-C1 5-Me CH2 2 H,H
4-Br 5-Me CH2C02Me H,H
4-CF3 H CH2 2 H,R

.

. 35 ., .
,`, ~

/

-- 2~

68 .
,:

1 R2 A B _ Ral, Ra2 ~ 4-Cl HCH2 CO2Et H,H
4-Br HCH2 CO2Et H,H
4-CF3 5-ClC~2 CO2Et H,H
4-C1 5-ClCH2 CO2Et H,H
4-Br 5-ClCH2 CO2Et H,H
4-CF3 HCH2 CO2-i-Pr O H,H
4-C1 2 2 H,H
. 4-Br HCH2 CO2-i-Pr O H,H .
. 4-CF3 H CH2 C2CH2CF3 H,H
: 15 4-Cl H CH2 C2CH2CF3 H,H
4-Br H CH2 C2CH2CF3 H,H ,!'`.. ;
4-CF3 H CH2 CO2allY1 H,H
4-Cl H CH2 CO2allyl O H,H
. 4-Br H CH2 CO2allyl O H,H ~.i .! 20 4-CF3 H CH2 C2CH2CH2C1 H,H
. 4-Cl H CH2 C2CH2CH2C1 H,H
, 4-Br H CH2 C2CH2CH2C1 H,H
`0'1 4-CF3 H CH2 Ph O H,H
4-C1 2 H,H
. 25 4-Br 2 H,H
:~. 4-CF3 5-Cl CH2 Ph O H,H
4-C15-ClCH2 Ph O H,H
4-Br5-ClCH2 Ph O H,H
4-CF3 H CH2 4-Cl-Ph O H,H
' 30 4-ClHCH2 4-Cl-Ph O H,H
4-BrHCH2 4-Cl-Ph O ~,H . .

.~. :.

, ` 35 :

.,~
,.
j .

z~ 4~

R2 A B X Ral, Ra2 : 5 4-CF3 5-CF3 CH2 4-Cl-Ph O H,H
4-C1 5-CF3 CH2 4-Cl-Ph O H,H
4-Br 5-CF3 CH2 4-Cl-Ph O H,H
4-CF3 H CH2 4-F-Ph O ~,H
4-Cl H CH2 4-F-Ph O H,H :
4-8r H CH2 4-F-Ph O H,H
4-CF3 2 0 H,Me 4-C1 2 H,Me 4-Br 2 H,Me .: 15 4-CF3 5-C1 2 Me,Me 4-C1 5-Cl CH2 H O - Me,Me 4-Br 5-Cl CH2 H O Me,Me 4-CF3 H CH2 H S H,H
- 4-Cl H CH2 H S H,H
. 20 4-Br H CH2 H S H,H
, 4-CF3 H CH2 Me S H,H :~
4-Cl H CH2 Me S H,H
4-Br H CH2 Me S H,H
1 4-CF3 H CH2 C2Me S H,H
., 25 4-Cl H . CH2 C2Me S H,H
4-Br H CH2 C02Me S H,H
~-- 4-CF3 5-Cl CH2 H S H,H
. 4-C1 5-Cl CH2 H S H,H
4-Br S-Cl CH2 H S H,H :
4-CF3 5-C1 2 S H,H

.
:
.

, . : , : : :. . . : . - .: ~ :: :: . : : ::

2~ i 4~1 Rl R2 A B X Ral, Ra2 4-C1 5-Cl CH2 Me S H,H
4-Br 5-Cl CH2 Me S H,H
4-CF3 5-Cl CH2 CO2Me S H,H
4-C1 5-Cl CH2 C~2Me S H,H
; 10 4-Br 5-Cl CH2 C02Me S H,H
~: 4-CF3 5-Me CH2 H S H,H ~ .
4-C1 5-Me CH2 H S H,H
4-Br 5-Me CH2 H S H,H
4-CF3 H O H O H,H
4-Cl H O H O H,H
4-Br H O H O H,H
:~ 4-CF3 5-Cl O H O H,H
" 4-C1 5-Cl O H O H,H
, 4-Br S-Cl O H O H,H
. 20 4-CF3 5-Br O H O H,H
: 4-C1 5-Br O H O H,H
4-Br 5-Br 0 H 0 H,H
, 4-CF3 5-CF3 0 H 0 H,H
4-C1 5-CF3 0 H 0 H,H
.~. .
4-Br 3 o H,H
4-CF3 H 0 Me 0 H,H
.. 4-Cl H 0 Me O H,H
'! 4-Br H O Me O H,H
4-CF3 5-Cl O Me H,H

`::
J ' ."' - 35 `~

, ~ .
.
. ' -:

i""'';'.'' ",',".','',''''.'' "'" ' '~ ''',' ', '', ; ', ' "., ~' "' '~'' '' '' . . - . i . .......... .... , .: ...... . .. .. : . .
- . : . . : :. - : - : . . .: , .

~ ` 2~ i4~

R R2 A B X Ral, Ra2 4-Cl S-Cl O Me O H,H
4-8r 5-Cl O Me O H,H
~ 4-CF3 5-Br O Me O H,H
4-C1 5-Br O Me O H,H
4-9r 5-Br O Me H,H
4-CF3 5-CF3 O Me O H,H
4-C1 5-CF3 O Me O H,H
4-Br 5-CF3 O Me O H,H
.: 4-CF3 5-F O Me O H,H
: 15 4-Cl S-F O Me H,H
4-Br S-F O Me O H,H
.~ 4-CF3 H 2 H,H
4-Cl H O CO2Me O H,H
.~ 4-Br H O CO2Me O H,H
4-CF3 5-Cl O 2 H,H
4-Cl S-Cl O CO2Me O H,H
., 4-Br 5-Cl O CO2Me O H,H
, 4-CF3 H O Ph O H,H
4-Cl H O Ph O H,H
4-Br H O Ph H,H
4-CF3 5-Br O Ph O ~,H
`. 4-C1 5-Br O Ph O H,H
`' 4-Br 5-Br O Ph O H,H

., .
~ 30 : ~ .

' ,~ ' . ' .
, .. ..

2~3~ 4~

Rl ~2 A B X Ral, Ra2 . . ~
4-CF3 H O H O Me,Me :
4-Cl H O H O Me,Me 4-Br H O H O ~e,Me --, 4-CF3 H O H O H,Me 4-Cl H O H O H,Me ,` 4-Br H O H O H,Me 4-CF3 H O H O H,Ph 4-Cl H O H O H,Ph 4-Br H O H O H,Ph 4-CF3 H O H O H,CO2Me , 15 4-Cl H O H O H,CO2Me ~, 4-~r H O H O H,CO2Me 4-CF3 H O H S H,H
~ 4-Cl H O H S H,H
: 4-Rr H O H S B,H ~.. -,~ 20 4-CF3 H S H O B,H
' 4-Cl H S H O H,H
.`i 4-Br H S H O H,H
!, 4-CF3 5-Cl S H O H,H .
;~ 4-C1 5-Cl S H O H,H ,~,~
4-Hr 5-Cl S H O H,H
4-CF3 5-Br S H O H,H
,, 4-C1 5-Br S H O H,H ; .
. 4-Br 5-Br S H O H,H
, ::
r .'1 ' ' ' ' 35 . :

,.; ; i ' , . .
. : j., . ~ , ~.. .
`'~.

2 t 3 . ~ ~ ~3 Rl R2 A B X Ral, Ra2 4-CF3 5-CF3 S H O H,H
4-Cl S-CF3 S H O H,H
4-Br 5-CF3 S H O H,H
4-CF3 H S Me O H,H
4-Cl H S Me O H,H
4-Br H S Me O H,H
4-CF3 5-Cl S Me O H,H
4-Cl S-Cl S Me O H,H
:~ 4-Br 5-Cl S Me O H,H ., 4-CF3 5-Br S Me O H,H
4-C1 5-Br S Me O H,H
4-Br 5-Br S Me O H,H
4-CF3 5-CF3 S Me O H,H
4-C1 5-CF3 S Me O H,H
4-Br 5-CF3 S Me O H,H
4-CF3 5-F S Me O H,H
.:
4-C1 5-F S Me O H,H
~` 4-~r 5-F S Me O H,H
4-CF3 H S 2 H,H
~ 25 4-Cl H S 2 H,H
:~ 4-Br H SCO2Me O H,H
: 4-CF3 5-C1 2 H,H
4-C1 5-Cl S CO2Me O H,H
. 4-Br 5-Cl S CO2Me O H,H
:. 30 4-CF3 H S Ph O H,H

.: :
.~ , . .
:"
` 35 ~ :

, : :.
,'~ ,.' .

: .:
'::

:, . . , ,, , , ,. . . , ,: . , - : . : . , , -Z ~ ~i L~ 3 :~.
1 R2 AB X Ral, Ra2 ' '' - .
4-Cl H SPh O H,H
4-Br H SPh O H,H
4-CF3 5-Br S Ph O H,H
4-C1 5-Br SPh O H,H
~: 4-Br 5-Br SPh O H,H .
: 4-CF3 H S H O Me,Me 4-Cl H S H O Me,Me 4-Br H S H O Me,Me 4-CF3 H S H O H,Me ~ :
4-Cl H S H O H,Me ~ 4-Br H S H O H,Me :. 4-CF3 H S H O H, Ph : .
4-Cl H S H O H,Ph 4-Br H S H O H,Ph ~ 4-CF3 H S H O H, C02Me . .
:. 2 0 4-Cl H S H O H,C02Me -.
::~ , . .
i' 4-Br H S H O H,C02Me ~`' 4-CF3 H S H S H,H
4-Cl H S H S H,H
' 4-Br H S H S H,H :
.~ 25 . . .

,~. . :, .
.:
' 30 :
. ~ .
, : ~1' :, . . .

, .
:, .

:i :. - .

-` 2~ 3 Table 4 Rl R2 A 8 X Ral, Ra2 , . _ . . . _ .
4-CF3 2 H,H
4-Cl HCH H O H,H
4-8r HCH2 H O H,H
10 4-CF3 4-Me2 H,H
4-C1 4-MeCH2 HO H,H
4-Br 4-MeCH2 HO H,H
4-CF3 4-FCH2 HO H,H
4-C1 4-FCH2 HO H,H
4-Br 4-FCH2 HO H,H
: 4-CF3 4-ClCH2 HO H,H
4-C1 4-Cl CH2 H O H,H
4-Br 4-Cl CH2 H O H,H
.~ 4-CF3 5-FCH2 HO H,H
20 4-C1 5-F 2 H,H
4-Br 5-FCH2 HO H,H
4-CF3 5-Cl CH2 H O H,H
4-C1 5-Cl CH2 H O H,H
.~; 4-Br 5-ClCH2 HO H,H
25 4-CF3 5-MeCH2 HO H,H
4-C1 5-Me CH2 H O H,H
4-8r 5-Me CH2 H O H,H
. 4-CF3 5-BrCB2 HO H,H
4-C1 5-Br CH2 H O H,H
5-BrCH2 HO H,H
:. 4-CF3 5-OMe 2 H,H
4-C1 5-OMe CH2 H O H,H
.- 4-Br 5-OMe CH2 H O H,H
4-cr3 HCH2 Me H,H

', ~' ~, ' ,: . :: . .: : : .
. . . . . i :

~ 2~2$~ 4-3 ~ R2A 8 X Ral, Ra2 4-Cl HCH2 Me O H,H
4-Br HCH2 Me O ~,H
4-CF3 4-FCH2 Me O H,H
4-C1 4-FCH2 Me O H,H
.~ 10 4-Br 4-F 2 0 H,H
:-: 4-CF3 5-F 2 0 H,H
4-Cl S-FCH2 Me O H,H
~ 4-Br 5-FCH2 Me O H,H
r 4-CF3 CH2 Me O H,H
4-Cl HCH2 Et H,H
4-Br HCH2 Et O H,H
4-CF3 4-F 2 H,H
, 4-C1 4-FCH2 Et O H,H
4-Br 4-FCH2 Et O H,H
4-CF3 4-ClCH2 Et H,H
'A`~ 4-C1 4-Cl CH2 Et O H,H
, 4-Br 4-Cl CH2 Et O H,H
., 4-CF3 H CH2 allyl O H,H
,~ 4-Cl H CH2 allyl O H,H
254-Br H CH2 allyl o H,H
.. 4-CF3 S-F CH2 allyl O H,H
~ 4-C1 5-F CH2 allyl O B,H
?~ 4-Br 5-F CH2 allyl O H,H
.. J 4-CF3 5-Cl CH2 allyl O H,H
., 30 4-Cl S-Cl CB2 allyl O H,H
;'.~' -,. , ; .

,. 35 .. ..

: S 1 _ _ 2 AB X Ral 4-Br 5-Cl CH2allyl O B,H
4-CF3 H CH2C02Me H,H
4-Cl H CH2C02Me H,H
4-Br H CH2C02Me H,H
4-CF3 4-F CH2C02Me H,H
4-C1 4-F CH22 H,X
4-8r 4-F CH22 H,H
4-CF3 4-F CH2C02Me H,H
4-C1 4-F CH22 H,H
~ 15 4-Br 4-F CH2C02Me H,H
; 4-CF3 5-F CH22 H,~
~; 4-C1 5-F CH22 H,H
4-8r 5-F CH2C02Me H,H
: 4-CF3 4-Cl ,CH22 H,H
4-C1 4-Cl CH2C02Me H,H
4-8r 4-Cl CH22 H,H
4-CF3 5-Cl CH2C02Me H,H
4-C1 5-Cl CH2C02Me H,H
4-Br 5-Cl CH2 2 H,H
4-CF3 5-CF3 CH2 C02Me H,H
4-C1 5-CF3 CH2 C02Me H,H
4-Br 5-CF3 CH2 2 H,H
4-CF3 5-Me CX2 2 H,H
4-C1 5-Me CH2 2 H,H
4-Br 5-Me CN2 C02Me H,H

' .: -Z~ 3 -Rl R2 A ~ X Ral, Ra2 ~
S . . _ , , 4-CF3 H CH2 CO2Et H,H
4-Cl H CH2 CO2Et H,H
4-Br H CH2 CO2Et X,H
: 4-CF3 5-Me CH2 CO2Et H,H
4-C1 5-Me CH2 CO2Et O ~,H
4-Br 5-Me CH2 CO2Et H,H
4-CF3 H CH2 CO2i-Pr O H,H
4-Cl H CH2 CO i-Pr o H,H
.. 4-Br H CH2 CO2i-Pr O H,H
15 4-CF3 2 2 2 3 H,H
4-C1 2 2 2 3 H,H
i 4-Br 2 2 2 3 H,H
4-CF3 H CH2 CO2allyl 0 H,H
: 4-Cl H CH2 CO2allyl O H,H
4-Br H CH2 CO2allyl O H,H
4-CF3 H CH2 CO2CH2CH2C1 H,H
4-Cl H CH2 C2CH2CH2C1 H,H
,' 4-Br H CH2 C2CH2CH2C1 H,H
:: 4-CF3 H CH2 Ph O H,H
4-Cl H CH2 Ph O H,H
4-Br H CH2 Ph O H,H
.,, 4-CF3 4-F CH2 Ph O H,H
4-C1 4-F CH2 Ph O H,H
4-Br 4-F CH2 Ph O H,H
4-CF3 H CH2 4-Cl-Ph O H,H
.. 4-Cl H CH2 4-Cl-Ph O H,H
' , `. .
.` :

,.. , , ,. , . ~ . ,,, ,, . ~ ~. . :

2~ 3 Ql R2 . A X X Ral, Ra2 4-Br H CH2 4-Cl-Ph O H,H
4-CF3 5-ClCH2 4-Cl-Ph O H,H
4-C1 5-ClCH2 4-Cl-Ph O H,H
: 4-Br 5-ClCH2 4-Cl-Ph O H,H
: 10 4-CF3 H CH2 4-F-Ph O H,H
4-Cl H CH2 4-F-Ph O H,H
4-Br H CH2 4-F-Ph O H,H
4-CF3 H CH2 H O H,Me 4-Cl H CH2 H O H,Me : 15 4-Br H CH2 H O H,Me 4-CF3 5-ClCH2 H O Me,Me . 4-C1 5-ClCH2 H O Me,Me :
4-Br 5-ClC~2 H O Me,Me 4-CF3 H CH2 H S H,H
4-Cl H CH2 H S H,H
4-Br H CH2 H S H,H
4-CF3 H CH2 Me S H,H
4-Cl H CH2 Me S H,H .
4-Br H CH2 Me S H,H
4-CF3 H CH2 CO2Me S H,H :~
4-Cl H CH2 CO2~e S H,H
4-Br H CH2 CO2Me S H,H
. 4-CF3 5-ClCH2 H S H,H
4-C1 5-ClCH2 H S H, H ;
4-Br 5-ClCH2 H S H,H

.` .
. .
., .

.~ .

J
~;.

~ '. ' ' ' ' " ' . ' ' ., ' :" . ' '~

:

Rl R2 A B X Ral, Ra2 . .
4-CF3 5-Cl CH2Me S H,H
4-C1 5-Cl CH2Me S H,H
: 4-Br 5-Cl CH2Me S H,H
4-CF3 5-Cl CH2 CO2Me S H,H
4-C1 5-Cl CH2 C02Me S H,H
4-Br 5-Cl CH2 C02Me S H,H
4-CF3 H 0 H O H,H
i 4-Cl H O H O H,H
4-Br H O H O H,H
- 15 4-CF3 5-Cl O H O H,H
4-C1 5-Cl O H O H,H
4-Br 5-Cl O H O H,H
4-CF3 4-F O H O H,H
~ 4-C1 4-F 0 H O H,H
.. 20 4-Br 4-F O H O H,H
. 4-CF3 5-CF3 0 H O H,H
4-C1 5-CF3 0 H 0 H,H
4-Br 5-CF3 0 H O H,H
4-CF3 H O Me O H,H
; 25 4-Cl H 0 Me H,H
4-Br H 0 Me O H,H
4-CF3 4-F O Me H,H
4-C1 4-F O Me O H,H
4-Br 4-F O Me 0 H,H

,~ :

', 35 ., .

,~ :
..

- ~ . . : . , . ' 4 ~

Rl R2 A B X Ral, Ra2 4-CF3 4-Cl O ~e O H,H
4-C1 4-Cl O ~e O ~,H
4-8r 4-Cl O Me O H,H
,. 4-CF3 5-F O Me O H,H
4-C1 5-F O Me O H,H
4-8r S-F O Me O H,H
4-CF3 S-Cl O Me O B,H
4-C1 5-Cl O ~b O ~,H
4-8r 5-Cl O ~e O H,H
4-CF3 H O CD2Me O ~,H
4-Cl H O CO2Me O ~,H
~; 4-Br H o CO2Me H,H
4-CF3 S-Cl O 2 H,H
4-C1 5-Cl O CO2Me O H,H
."~ 20 4-Br 5-Cl O 2 H,H
` 4-CF3 H O Ph O H,H
~ 4-Cl H O Ph O H,H
;~ 4-Br H O Ph. O H,H
. 4-CF3 5-Cl O Ph O H,H '~
., 25 4-C1 5-Cl O Ph H,H
4-Br 5-Cl O Ph H,H
4-CF3 H O H O Me,Me ~ 4-Cl H O ~ O Me,Me .. ~ 4-Br H O R O Me,Me '~ 30 4 CF H O H O H,Me ,~ 4-Cl H O H O H,Me -~: 4-Br H O H O H,Me 4-cr3 H O H O H, Ph 4-Cl H O ~ O H,Ph 4-Br H O H O H,Ph - - .
3 H o ~ ~ H,CO2Me 4-Cl H O ~ O ~,CO2Me 4--Br H O ~ O H,CO2Me , ~ ~
~'' .

~, ' '.:
., .

' $~ 9 .
: '. , Rl 22 A 8 X Ral, Ra2 4-CF3 H O H S H,H
4-Cl H O H S H,H
4-Br H O H S H,H
4-CF3 H S HO H,H
4-Cl H S H O H,H
: 4-Br H S H O H,H
~: 4-CF3 5-Cl S H O H,H
;:: 4-C1 5-Cl S H O H,H
. 4-Br 5-Cl S H O H,H
4-CF3 4-F S H O H,H
4-C1 4-F S H O H,H :.
4-Br 4-F S H O H,H :~.
4-CF3 5-CF3 S H O H,H
; 4-C1 5-CF3 S H O H,H
4-Br 5-C~3 S H O H,H
4-CF H S Me O H,H
: 3 ;~ 4-Cl H S Me O H,H
.' 4-Br H S Me O H,H
c 4-CF3 4-F S Me O H,H
;. 2~ 4-C1 4-F S Me O X,H
. 4-Br 4-F S Me O H,H -4-CF3 4-Cl S Me O H,H
4-C1 4-Cl S Me O H,H
4-Br 4-Cl S Me O H,H
.~ 30 4-CF3 5-r S Me O H,H
4-C1 5-F S Me O ~,H
4-Br S-F S Me O H,H
- 4-CF3 5-Cl S Me O X, H
. 4-C1 5-Cl S Me O H,H
4-Br 5-Cl S Ne O H, H
4-CF3 H S 2 H,H
,: .
., "~ :
. ' .
.
~ . -, . ~ . . . : - ~: . .

2~c~

Rl R2 A B :K Ral, Ra2 .
4-Cl H S C02Me O H,H
4-Br H S 2 H,B
4-CF3 5-C1 2 H,H
4-C1 5-Cl S C02Me O H,H
4-Br 5-C1 2 H,H
4-CF3 H S Ph O H,H
4-Cl H S Ph O H,H
4-Br H S Ph O H,H
4-CF3 5-Cl S Ph O H,H
:. 15 4-C1 5-Cl S Ph O H,H .
4-Br 5-Cl S Ph O H,H
4-CF3 H S H O Me,Me 4-Cl H S H O Me,Me 4-Br H S H O Me,Me 4-CF3 H S H O H,Me : 4-Cl R S H O H,Me :~ 4-Br H S H O H,Me . 4-CF3 H S H O H,Ph . 4-Cl H S H O H,Ph 4-Br H S H O H,Ph . 4-CF H S H O H,CO Me :~ 25 3 2 ^ 4-Cl H S H O H,C02Me . 4-~r H S H O H,C02Me 4-CF3 H S H S H,B
4-Cl H S H S H,H
: 4-Br H S H S H,H
30 ..

:,, , :: :

- : , ' :- ' - : . ~: .. " ' . . ~ ' ::

; Table 5 Rl R2 A B X Ral, Ra2 4-CF3 H C~2 H O H,H
4-Cl H CH2 B O H,H
4-Br H CH2 H O H,H
4-CF3 S-Cl CH2 H O H,H
4-Cl S-Cl C~2 H O H,H
4-Br 5-Cl CH2 H O H,H
4-CF3 5-F 2 O H,H
.. 4-Cl S-F CH2 H O H,H
; 4-Br 5-F CH2 H O H,H
~ 15 4-CF3 S-Me CH2 H O H,H
: 4-C1 5-Me CH2 H O H,H
4-Br S-Me CH2 ~ H,H
: 4-CF3 H CH2 Me O H,H
`. 4-Cl H CH2 Me O N,H
4-Br H CH2 Me O ~,H
:,.: 4-CF3 S-Cl CH2 Me O H,H ;.`
4-Cl S-Cl CH2 Me O H,H
4-Br 5-Cl CH Me O H,H
.; 2 s 4-CF3 S-F CH2 Me O H,H
., 25 4-Cl S-F CH2 Me O H,H
-., 4-Br S-F CH2 Me O H,H
. 4-CF3 S-Me C~2 Me H,H
, ! 4-Cl S-Me CH2 Me O H,N
', 4-Br S-Me CH2 Me O H,H
4-CF3 H CH2 Et O H,H
4-Cl H CH2 Et O H,H
. 4-Br H CH2 Et O H,H
4-CF3 H CH2 CO2Me H,H

, .
. ' ., Z~ -9 . :
Rl R2 - A 8 X Ral, R~2 4-Cl H CH2 2 H,H
4-Br H CH2 2 H,H
4-CF3 5-F CH2 2 H,H
4-C1 5-F CN2CO2Me H,H
4-Br 5~P CH2CO2Me H,H
~; 4-CF3 5-Cl CH2CO2Me H,H
4-C1 5-Cl CH2 2 H,H
4-Br S-Cl CH2CO2Me H,H
~ 4-CF3 5-Me CH2CO2Me H,H
:~- 15 4-C1 5-Me CH2CO2Me H,H
4-Br 5-Me CH2 2 H,H
- 4-CF3 5-Cl CH2C2~t H,H
4-C1 5-Cl CH2CO2Et H,H
. 4-Pr 5-Cl CH2 2 H,H
~, 20 4-CF3 H CH2 Ph O H,H
' 4-Cl H C92 Ph O H,H -4-Br H CH2 Ph O H,H
4-CF3 5-Cl CH2 Ph O H,H
~ 4-C1 5-Cl CH2 Ph O H,H
'J 25 4-Br 5-Cl CH2 Ph o H,H
4-CF3 H CH24-Cl-Ph O H,H
"~ 4-Cl H CH24-Cl-Ph O H,H :
~! 4-Br H CH24-Cl-Ph O H,H
~, 4-CF3 5-Cl CH24-Cl-Ph O H,H
' 30 4-C1 5-Cl CH24-Cl-Ph O H,H
.~ 4-Br S-Cl CH24-Cl-Ph O H,H
4-CF3 2 2 H O H,H
4-CF3 H O H O H,H
4-CF3 H O Me O H,H

4-CF3 H O i-Pr O H,H
4-CF3 H O CO2Me H,H

, .

2~ .4 ~

Rl R2 A B X R~l, Ra2 4-CF H O Ph O H,H
4-CF3 H O 4-F-Ph O H,H
4-CF3 R O 4-Cl-Ph O H,H
4-CF3 5-F O H O H,H
4-CF3 5-F O Me O H,H
4-CF3 5-F O i-Pr O H,H
4-CF3 5-F O 2 H,H
: 4-CF3 5-F O Ph O H,H
4-CF3 5-F O 4-F-Ph O H,H
4-CF3 5-F O 4-Cl-Ph O H,H
4-CF3 5-Cl O H O H,H
4-CF3 S-Cl O Me O H,H
4-CF3 5-Cl O i-Pr O H,H
':~ 4-CF3 5-C1 2 H,H
4-CF3 5-Cl O Ph O H,H
. 4-CF3 5-Cl O 4-F-Ph O H,H
; 4-CF3 5-Cl O 4-Cl-Ph O H,H
4-OCF3 H O H O H,B
, 4-OCF3 H O Me O H,H
4-OCF3 H O i-Pr O H,H
" 4-OCF3 H O C2Me H,H
, 4-OCF3 H O Ph O H,H
,, 4-OCF3 H O 4-F-Ph O H,H
: 4-OCF3 B . 0 4-Cl-Ph O H,J~
4-OCF3 5-F O H O H,H
4-OCF3 5-F O Me O H,H
4-OCF3 5-F O i-Pr O H,H
4-OCF3 5-F O C2Me H,H
4-OCF3 5-F O Ph O H,H
. 35 4-OCF3 5-F O 4-F-Ph O H,H

4-OCF3 5-F O 4-Cl-Ph O H,H

. , : ~ :
., :
. ......... ~ . ~
., , .
- . , ,. .- ;:

.: , ' . ' , ' , 4 ~

Rl R2 A B X Ral, Ra2 4-OCF3 5-Cl O H o H,H
4-OCF3 5-Cl O Me O H,H
4-OCF3 5-Cl O .i-Pr O H,H
3 2 H,H
4-OCF3 5-Cl O Ph O M,H
4-OCF3 5-Cl O 4-F-Ph O H,H
4-OCF3 5-Cl O 4-Cl-Ph O H,H
: 4-Br H O H O H,H
4-Br H O Me O H,H
: 15 4-Br H O i-Pr O H,H
~ 4-Br H O CO2Me O H,H
; 4-Br H O Ph O H,H
~ 4-Br H O 4-F-Ph O H,H
;

. 4-Br H O 4-Cl-PhO H,H
4-9r 5-F O HO H,H

4-Br 5-F O MeO H,H
; 4-Br 5-F O i-PrO H,H
4-Br 5-F O 2 H,H
-. 4-9r 5-F O PhO H,H
`` 25 4-Br 5-F O 4-F-PhO H,H
4-Br 5-~ O 4-Cl-PhO H,H
4-Br 5-Cl O HO H,H
4-Br 5-Cl O MeO H,H
4-Br 5-Cl O i-PrO H,H
4-Br 5-C1 2 H,H
: 4-Br 5-Cl O PhO H,H
4-Br 5-CI O 4-F-PhO H,H
. 4-Br 5-Cl O 4-Cl-PhO H,H
4-Cl H O HO H,H
4-Cl H O MeO H,H
4-Cl H O i-PrO H,H
,~ 4-Cl K O CO2Me H,H

, . . .

, . .

2~ q3 Rl R2 A B X Ral, Ra2 4-Cl H O Ph O H,H
4-Cl H O 4-F-Ph O H,H
4-Cl H O 4-Cl-Ph O H,H
4-C1 5-F O H O H,H
4-C1 5-F O Me O H,H
4-C1 5-F O i-Pr . O H,H
4-C1 5-F O CO2Me O H,H
~: 4~C1 5-F O Ph O H,H
4-C1 5-F O 4-F-Ph O H,H
4-C1 5-F O 4-Cl-Ph O H,H
4-C1 5-Cl O H O H,H
4-C1 5-Cl O Me O H,H
4-C1 5-Cl O i-Pr O H,H
; 4-C1 5-Cl O C02Me O H,H
4-C1 5-Cl O Ph O H,H
4-C1 5-Cl O 4-F-Ph O H,H
4-C1 5-Cl O 4-Cl-Ph O H,H
,:~

. 25 ,~ '-,,~ ' , .

," .
~, ,'~ ' ....
, ~ 2~C~ . 4 ~

Table 6 : 5 Rl R2 A B X R~l, Ra2 4-CF3 H CH2 H O H,H
4-Cl H CH2 H O H,H
4-Br H CH2 H O H,H
~ 10 4-CF3 4-F C~2 H O H,H
; 4-C1 4-F CH2 H O H,H
4-Br 4-F CH2 H O H,H
4-CF3 4-Cl CB2 ~ O ~,H
. 4-C1 4-Cl C~2 H O H,H
4-Br 4-Cl CH2 H O H,H
4-CF3 4-Me CH2 H O H,H
. 4-C1 4-Me CH2 H O H,H
4-Br 4-Me CH2 H O H,H
.~ 4-CF3 H CH2 Me H,H
~` 20 4-Cl H CH2 Me O H,H
4-Br H ,CH2 Me O H,H
4-CF3 4-F CH2 Me O H,H
4-C1 4-F CH2 Me H,H
. 4-Br 4-F CH2 Me O H,H
.i 25 4-CF3 4-Cl CH2 Me ~,H
4-C1 4-Cl CH2 Me O H,H
4-Br 4-Cl CH2 Me O H,H
. 4-CF3 H CH2 Et O H,H
; 4-Cl H CH2 Et O H,H
3n 4-Br H CH2 Et H,H
.~ 4-CF3 4-F CH2 Et O H,H
.: 4-C1 4-F CH2 Et O ~!H
4-Br 4-F CH2 Et O H,H
4-CF M C112 COzMe O ii, H

." ' ~,;

. ~

.".,.,..",..'",,~ . ,'.'.' ~'"''''''',", ,, ;'-"''~'.',"' , :. .. : . . . . . , .. . .... : .. .. .. ... . . . -. .. .. .. ", . - , , , ,, , ~ , 2 ~ 9 . .

Rl R2 A B X R~, Ra2 4-Cl H CH2 2 H,H
4-Br H CH2 2 H,H
4-CF3 4-F CH2 C2Me O H,H
4-C1 4-FCH2 2 H,H
4-9r 4-FCH2 CO2Me O H,H
4-CF3 4-ClC~2 2 H,H
4-C1 4-C1 2 2 H,H
- 4-Br 4-ClCH2 2 H,H
4-CF3 4-MeCH2 2 H,H
; 15 4-C1 4-MeCH2 2 H,H
- 4-Br 4-MeCH2 2 H,H
4-CF3 H CH2 2 H,H
4-Cl H CH2 2 H,H
4-Br H CH2 2 H,H
4-CF3 4-ClCH2 Ph O H,H
4-C1 4-ClCH2 Ph O H,H
.~
~ 4-Br 4-ClCH2 Ph O H,H
.~ 4-CF3 H CH2 Ph O H,H
.i~ 4-Cl H CH2 Ph O H,H
r,i 25 4-Br H CH2 Ph O H,H
.. 4-CF3 4-ClC~2 4-F-Ph O H,H
.~ 4-C1 4-ClCH2 4-F-Ph O H,H
4-Br 4-Cl CH2 4-F-Ph O H,H
.j 4-CF3 H CH2 4-F-Ph O H,H
4-Cl H CH2 4-F-Ph O H,H
; 4-Br H CH2 4-F-Ph O H,H
:

. .

~ 2 ~ .'L4 3 Table 7 Rl R2 A B X Ral, Ra2 _ . , 4-CF3 H CH2 H O H,H ,~.
4-Cl H CH2 H O H,H
4-Br H CH2 H O H,H
4-CF3 4-F CH2 H O H,H
4-C1 4-F CH2 H O H,H
4-Br 4-F CH2 H O H,H
: 4-CF3 5-Cl CH2 H O H,H
4-C1 5-Cl CH2 H O H,H
. 4-Br 5-Cl CH2 H O H,H
4-CF3 5-F CH2 H O H,H
4-C1 5-F CH2 H O H,H
4-Br S-F CH2 H O H,H
.-~ 4-CF3 H CH2 Me O H,H
4-Cl H CH2 Me O H,H
4-Br H CH2 Me O H,H
.. 4-CF3 4-F CH2 Me O H,H
4-C1 4-F CH2 Me O H,H
4-Br 4-F CH2 Me O H,H - .
4-CF3 4-Cl CH2 Me O H,H
4-C1 4-Cl CH Me O H,H
2 ..
4-Br 4-Cl CH2 Me O H,H
. 4-CF3 5-F CH2 Me O H,H
4-C1 5-F CH2 Me O H,H
.~ 4-Br 5-F CH2 Me O H,H `~
4-CF 5-Cl CH2 Me O H,H ' 4-C1 5-Cl CH2 Me O H,H

- :

:: : . . . .~ ... : . . :.. .: .. ~ : . . - .. , . --: , ~ : . . . , , .:: :, . :

9z Rl 2 A BX Ral, R~2 4-Br 5-Cl CH2Me O H,H
4-CF3 H CH2CO2Me H,H
4-Cl H C~2CO2Me H,H
4-Br H CH2 2 H,H
10 4-CF3 4-F CH2 2 H,H
4-C1 4-F CH2CO2Me H,H
4-Br 4-F CH2CO2Me H,H
4-CP3 4-Cl C~2CO2Me H,H
4-C1 4-Cl C~2CO2Me H,H
4-Br 4-Cl CH2CO2Me H,H
.~ 4-CF3 5-F CH2 2 H,H
.. 4-C1 5-F CH2CO2Me H,H
4-Br 5-F CH2CO2Me H,H
: 4-CF3 5-Cl CH2CO2Me H,H
4-C1 5-Cl CH2CO2Me H,H .~ .
4-Br 5-Cl CH2 2 H,H
4-CF3 H CH2Ph O H,H
4-Cl H CH2Ph O H,H
4-Br H CH2Ph O H,H
4-CF3 4-F CH24-F-PhO H,H
4-C1 4-F CH24-F-PhO H,H
4-Br 4-F CH24-F-PhO H,H
. 9-CF3 5-Cl CH2 4-Cl-Ph O H,H
4-C1 5-Cl CH2 4-Cl-Ph O H,H
4-Br 5-Cl CH2 4-Cl-Ph O H,H
4-CF3 5-F CH2 4-Cl-Ph O H,H
~; 4-C1 5-F CH2 4-Cl-Ph O H,H
~` 4-Br 5-F CH2 4-Cl-Ph O H,H
.
: 35 ''~, ' ', ' , .

. ~.
:

~ - . . ... .. . . - .

--` 2i~J ~4~3 93 :

Rl R2 A B XRal, Ra2 4-CF3 H O H OH,H
4-CF3 H O Me OH,H
4-CF3 H O i-Pr OH,H

4-CF3 H O CO2Me H,H
4-CF3 H O Ph OH,H
4-CF3 ~1 O 4-F-Ph OH,H
4-CF3 H O 4-Cl-Ph OII,H
4-CF3 5-F O H OH,H
4-CF3 5-F O Me OH,H
4-CF 5-F O i-Pr OH,H
4-CF3 5-F O 2 H,H
4-CF3 5-F O Ph OH,H
. 4-CF3 5-F O 4-F-Ph OH,H ~ i 4-CF3 5-F O 4-Cl-Ph OH,H ~ ~i .
4-CF3 5-Cl O H 0H,H ~ ~:
.. 4-CF3 5-Cl O Me OH,H
4-CF3 5-Cl O i-Pr OH,H
, 4-CF3 S-Cl O C2Me H,H ~
.,~ 4-CF3 5-Cl O Ph . OH,H . ~ -4-CF3 5-Cl O 4-F-Ph OH,ll ~,' 4-CF3 5-Cl O 4-Cl-Ph OH,H ..
,~ 4-OCF3 H O HO H,H .
4-OCF3 H O Me O H,H
4-OCF3 H O i-Pr O H,H
3 0 4-OCF3 H CO2Me H,H
. 4-OCF3 11 0 Ph O . H,H
4-OCF3 H O 4-F-Ph O H,H
, 4-OCF3 H O 4-Cl-Ph O H,H

' 4-OCF3 5-F O HO H,H '. .
. 35 4-OCF3 5-F O Me O H,H
;, 4-OCF3 5-F O i-Pr O H,H .
. . ' ' ." ,. ..

2`~

Rl R2 A B X Ral, Ra2 4-oCF3 5-F O 2 H,H
4-OCF3 5-F O Ph O H,H
4-OCF3 5-F O 4-F-Ph O H,H
: 4-OCF3 5-F O 4-Cl-Ph O H,H
4-OCF3 5-Cl O H O H,H
4-OCF3 5-Cl O Me O H,H
4-OCF3 5-Cl O i-Pr O H,H
3 CO2Me O H,H
4-OCF3 5-Cl O Ph O H,H
4-OCF3 5-C1 O 4-F-Ph O H,H
: 4-OCF3 5-C1 O 4-Cl-Ph O H,H
4-Br H O H O H,H
4-Br H O Me O H,H
4-Br H O i-Pr O H,H
4-Br H O CO2Me H,H
4-Br H O Ph O H,H
4-Br H O 4-F-Ph O H,H
4-Br H O 4-Cl-Ph O 8,H
4-Br 5-F O H O H,H
2~ 4-Br 5-F O Me O H,H
4-Br 5-F O i-Pr O H,H
: 4-Br 5-F O CO2Me O H,H
- 4-8r 5-F O Ph O H,H
., 4-Br 5-F O 4-F-Ph O H,H
4-Br 5-F O 4-Cl-Ph O H,H
4-Br 5-Cl O H O H,H
4-8r 5-Cl O Me O H,H
4-Br 5-Cl O i-Pr O H,H
4-8r 5-Cl O CO2Me O H,H
4-Br 5-Cl O Ph O

4-Br 5-C1 O 4-F-Ph O H,H
4-Br 5-C1 O 4-Cl-Ph O H,H

" : '' ' `. ` ' . ' - . '- ~ `' ` ::: , , . :.

-~ 2~3.j~ 4~ :

Rl R2 A B X ~ 1 . 5 4-Cl H 0 H .0 H,H
4-Cl H 0 Me O H,H
4-Cl H O i-Pr O H,H
4-Cl H O CO2Me H,H
4-Cl H O Ph O H,H
4-Cl H O 4-F-Ph O H,H
4-Cl H O 4-Cl-Ph0 H,H
` 4-C1 5-F O H O H,H
4-Cl S-F O Me O H,H
4-C1 5-F O i-PrO H,H
4-C1 5-F O 2 H,H
4-C1 5-F O Ph O H,H
4-C1 5-F 0 4-F-PhO H,H
. ..
:~ . 4-C1 5-F 0 4-Cl-PhO H,H
4-C1 5-Cl O H 0 H,H
. 4-C1 5-Cl O Me O H,H
4-C1 5-Cl O i-PrO H,H
4-C1 5-Cl 0 CO2MeO H,H
, 4-C1 5-Cl O Ph O H,H
~',' 25 4-C1 5-Cl O 4-F-PhO H,H
4-C1 5-Cl O 4-Cl-PhO H,H

... . . .
:~q .. . ..
-i 30 ''~ , .

.. :.

,~, .
. .
" . .
... .
.
' . ~"

' 2~-~ 34-~3 Table B ;, Rl R2 A BX Ral, Ra2 4-CF3 H CH2 HO H,H
4-Cl H CH2 HO H,H
4-Br ~ CH2 HO H,H
4-CF3 5-C1 2 H,H
4-C1 5-ClCH2 HO H,H
4-Br 5-ClCH2 HO H,H
4-CF3 5-FCH2 HO H,H
4-C1 5-F 2 ~,H
4-Br 5-FCH2 HO H,H
: 15 4-CF3 5-MeCH2 HO H,H
: 4-C1 5-MeCH2 HO H,H
4-9r 5-MeCH2 HO H,H
.: 4-CF3 H CH2 MeO H,H
4-Cl H CH2 MeO H,H
4-Br H CH2 MeO H,H
. 4-CF3 5-ClCH2 MeO H,H
4-C1 5-ClCH2 MeO H,H
4-Br 5-ClCH2 MeO H,H .
. 4-CF3 5-FCH2 MeO H,H
4-C1 5-FCH2 Me O H,H
4-Br 5-FCH2 Me O H,H
4-CF3 5-MeCH2 Me O H,H
4-C1 5-MeCH2 Me O H,H ..
. 4-Br 5-MeCH2 Me O H,H
~ 30 4-CF H CH2 Et O H,H
.. 4-Cl H CH2 Et O H,H
4-Br H CH2 Et O H,H
4-CF3 ~ CH2 COzMe O H,H
~` .

.' .

' ' 2~
97 ..
.

R2 A B X Ral, Ra2 4-Cl H CH2 2 H,H
4-8r H CH2 2 H,H
4-CF3 5-F CH2 2 H,H
4-C1 5-F CH2 2 H,H
4-Br 5-F CH2 2 H,H
4-CF3 5-ClCH2 2 H,H
4-Cl S-ClCH2 2 H,H
- 4-Br S-Cl 2 2 H,H
g-CF3 5-MeCH2 2 H,H
4-C1 5-MeC~2 2 H,H
4-Br 5-MeCH2 2 H,H
4-CF3 5-ClCH2 2 H,H
',~ 4-C1 5-ClCH2 2 H,H
. 4-Br 5-ClCH2 2 H,~
4-CF3 H CH2 Ph O H,H
4-Cl H CH2 Ph O H,H
4-Br H CH2 Ph O H,H
4 CF3 5-ClCH2 Ph O H,H
; 4-C1 5-ClCH2 Ph O H,H
; 25 4-8r 5-ClCH2 Ph O H,H
. 4-CF3 H CH2 4-Cl-PhO H,H
., 4-Cl H CH 4-Cl-PhO H,H
. 2 4-Br H CH2 4-Cl-PhO H,H
; 4-CF3 5-ClCH2 4-Cl-PhO H,H
4-C1 5-ClCH2 4-Cl-PhO H,H
~ 4-Br 5-ClCH2 4-Cl-PhO H,H
., , ~" 35 ,, :' :
~ ':
,,-. , .~

. .
., X~ 9 Table 9 Rl R2 A B X Ral, Ra2 . .
4-CF3 H CH2 H O H,H
4-Cl H CH2 H O H,H
4-8r H CH2 H O H,H

4-CF3 4-F CH2 H O H,H
4-C1 4-F CH2 H O H,H
4-8r 4-F CH2 H O H,H
::~ g-CF3 4-Cl CH2 H O H,H
~ 4-C1 4-Cl CH2 H O H,H
', 15 4-8r 4-Cl CH2 H O H,H
4-CF3 4-Me CH2 H O H,H
4-C1 4-Me CH2 H O H,H
4-Br 4-Me CH2 H O H,H
4-CF3 H CH2 Me H,H
~': 4-Cl H CH2 Me H,H
4-Br H CH2 Me O H,H
, 4-CF3 4-F CH2 Me H,H
4-C1 4-F CH2 Me H,H
4-Br 4-F CH2 Me H,H
.^ 4-CF3 4-Cl CH2 Me O H,H
., 25 4-C1 4-Cl CH2 Me O H,H
4-Br 4-Cl CH2 Me O H,H
,~. 4-CF3 H CH~ Et O H,H
4-Cl H CH2 Et O H,H
4-nr H CH2 Et O H,H
.~ 30 4-CF3 4-F CH2 Et H,H
4-C1 4-F CH2 Et O H,H
, 4-Br 4-F CH2 Et O H,H
'~ 4-CF3 ~ CH~ 2 Q H,H
.. . .

~ ~

' .
~.

,, , :

., . :, . , . ~: . : : . :.: . . : : . . ; : - .

~ Z~i ~4 ~

.

`~ 5 Rl R2 A B X Ral, Ra2 4-Cl H CH2 2 H,H
4-Br H CH2 CO2Me O H,H
4-CF3 4-F CH2 2 H,H
4-C1 4-F CH2 2 H,H
. 10 4-Br 4-F CH2 2 B,H
. 4-CF3 4-Cl CH2 2 H,H
4-C1 4-Cl CH2 2 H,H
. 4-Br 4-Cl CH2 2 ~,H
q-CF3 4-Me CH2 2 H,H
4-C1 4-Me CH2 2 H,H
4-8r 4-Me CH2 2 H,H
.~ 4-CF3 H CH2 2 B,H ,.. 4-Cl H CH2 2 H,H
4-Br H CH2 2 H,H
4-CF3 4-Cl CH2 Ph O H,H
. 4-C1 4-Cl CH2 PhO H,H
, -. ...
4-Br 4-Cl CH2 PhO H,H
4-CF3 H CH2 PhO H,H
~ 4-Cl H CH2 PhO H,H
., 25 4-Br H CH2 PhO H,H
4-CF3 4-Cl CH2 4-F-Ph O H,H
4-C1 4-Cl CH2 4-F-Ph O H,H
4-Br 4-Cl CH2 4-F-Ph O H,H ;
.~ 4-CF3 H CH2 4-F-Ph O H,H
,. 30 4-Cl H CH2 4-F-Ph O H,H -:

- 4-Br H CH2 4-F-Ph O H,H

:'.
. . .

.. . .

:, , ' .:, : ' ' ' .: ' ' ~, '' . :, , - 2~ q49 Table lO
1 R2 A B X Ral, Ra2 . 4-CF3 H CH2 H O H,H
4-Cl H CH2 H O H,H
4-Br H CH2 H O H,H

0 4-CF3 4-F CH2 H O H,B
4-C1 4-F CH2 H O H,X
4-Br 4-F CH2 H O H,H
.~ 4-CF3 5-Cl CH2 H O H,H
4-C1 5-Cl CH2 H O H,B
4-Br 5-Cl CH2 H O H,H
4-CF3 5-F CH2 H O H,H
~ 4-C1 5-F CH2 H O H,H
-j 4-Br 5-F CH2 H O H,H
4-CF3 H CH2 Me O H,H
4-Cl H CH2 Me H,H
4-Br H CH2 Me O H,H
4-CF3 4-F CH2 Me O H,H
4-C1 4-F CH2 Me O H,H
;~ 4-Br 4-F CH2 Me H,H
~ 4-CF3 4-Cl CH2 Me O H,H
: 25 4-C1 4-Cl CH2 Me ~ H,H
4-Br 4-Cl CH2 Me O H,H
. 4-CF3 5-F CH2 Me H,H
~ 4-C1 5-F ~H2 Me O H,H
`. 4-Br 5-F CH2 Me O H,H
4-CF3 5-C1 2 Me O H,H
4-C1 5-Cl CX2 Me O H,H
4-Br 5-Cl CH2 Me O H,H
. 4 CF3 H CH2 2 H,N

: 35 '~ '"

;. "

,. . .

" ~' . ,: ' . ' . ' :-: ' '' ' '' ' ' ' ' ': -. . ': . . ' . , . ,. , . . . : ' . . ' ' . ' ~ . . ' ' 2 ~ ~3 ~ :L 4 3 101 ,`
. .;

Rl R2 A B X Ral, R 2 . - . .
4-Cl H CH2 2 H,~ , 4-Br H CH2 2 H,H
4-CF3 4-F CH2 2 H,H
4-Cl q-F CH2 2 H,H
4-Br 4-F CH2 2 H,H
4-CF3 4-ClCH2 COzMe O H,H
. 4-C1 4-Cl CH2 2 H,H
.. ` 4 8r 4-Cl CH2 2 H,H
~ 4-CF3 5-F CH2 2 H,H
,~ 15 4-C1 5-F CH2 2 H,H
. 4-Br 5-F CH2 2 H,H
,.`~ 4-CF3 S-Cl CH2 2 H,H
`, 4-C1 5-Cl CH2 2 H,H
4-Br S-Cl CH2 2 H,H
4-CF3 H CH2 Ph O H,H ;
,' 4-Cl H CH Ph O H,H
. 2 .
4-Br H CH2 Ph O H,H , cl 4-CF3 4-F CH2 4-F-Ph O H,H . :
4-C1 4-F CH24-F-PhO H,H
`'J 4-Br 4-F CH2 4-F-Ph O H,H
,~ 4-CF35-Cl CH2 4-Cl-Ph O H,H
~i, 4-C1 5-Cl CH2 4-Cl-Ph o H,H
'; 4-Br 5-Cl CH2 4-Cl-Ph O H,H
4-CF1 5-F CH2 4-Cl-Ph O H,H
~! ~ ' 30 4-C1 5-F C~2 4-Cl-2~ O H,H
4-Br 5-F CH24-Cl-Ph O H,H
: , .

,,; .
.. . .
j .
.
'` 35 :~

. 7.
": "', . ' .

.' . ' ;' '.' : ' . , ' , . . .. '' ' ' ' 2 ~ t' ~ JL ~ ~I

Table 11 Rl R2 A B Q Y
4-CF3 HCH2 H Q-l Me 4-Cl HCH2 H Q-l Me 4-Br HCH2 H Q-l ~e 4-CF3 5-C1 2 Q-1 Me 4-C1 5-ClCH2 Me Q-l Me 4-~r 5-ClCH2 Me Q-l Me 4-CF3 HCH2 Me Q-l Me 4-Cl BCH2 Me Q-l Me 4-Br HC~2 Me Q-l Me 4-CF3 HCH2 Me Q-l ClO)Me 4-Cl HCH2 Me Q-l C(O)Me 4-Br HCH2 Me Q-l C(O)Me 4-CF3 HCHz Me Q-l CO2Me 4-Cl j~ 2 Q-l CO2Me . ;
4-Br HCH2 Me Q-l C2Me ~` 4-CF3 5-C1 2 Q-l Me 4-C1 5-ClCH2 Me Q-l Me 4-Br 5-ClCH2 Me Q-l Me . 4-CF3 5-C1 2 Q-l C(O)Me : 25 4-C1 5-C1 2 Q-1 C(O)Me 4-~r 5-ClCH2 Me Q-l C(O)Me j 4-CF3 5-ClCH2 Me Q-l C02Me .`. 4-C1 5-ClCH2 ~e 0-1 C2Me 4-Br 5-C1 2 0-1 C2Me , 30 4-CF3 5-F 2 Q-l C2Me ,~ 4-C1 5-F 2 0-1 C2Me 4-Br 5-F 2 Q-l C2Me 4-CF3 H CH2 C2Me Q-l C(O)Me .
.. :
` 35 ' ~ :

, ~'' .

, ' ;

:, .

~ 4-~) 5 Rl R2 A B Q Y
4-Cl H CH2 C2Me Q-l C(O)Me 4-8r H CH2 C2Me Q-l C(O)Me . 4-CF3 H CH2 CO2Me Q-l Me :
. 4-Cl H CH2 CO2Me Q-l Me 10 4-Br H CH2 C02Me Q-l Me 4-CF3 H CH2 C02Me Q-l CO2Me 4-Cl H CH2 C02Me Q-l C2Me : 4-Br H CH2 C2Me Q-l C2Me 4-CF3 5-Cl CH2 C02Me Q-l C(O)Me 15 4-C1 5-Cl CH2 CO2Me 0-1 C(O)Me 4-Br 5-Cl CH2 C02Me Q-l C(O)Me 4-CF3 5-Cl CH2 CO2Me Q-l CO2Me 4-C1 5-Cl CH2 C2Me Q-l C2Me 4-Br 5-Cl CH2 C02Me Q-l C2Me . 20 4-CF3 H CH2 Ph Q-l C(O)Me 4-Cl ~ CH2 Ph Q-l C(O)Me ' 4-Br H C82 Ph 0-1 C(O)Me 4-CF3 5-Cl CH2 Ph Q-l C(O)Me 4-C1 5-Cl CH2 Ph Q-l C(O)Me . 25 4-Br 5-Cl CH2 Ph Q-l C(O)Me s~ 4-CF3 H CH2 4-Cl-Ph Q-l C(O)Me 4-Cl H CH2 4-Cl-Ph Q-l C(O)Me ' 4-Br H CH2 4-Cl-Ph Q-l C(O)Me ; 4-CF3 5-CI CH2 4-Cl-Ph Q-l C(O)Me -: 30 4-C1 5-Cl CH2 4-Cl-Ph Q-l C(O)Me ., 4-Br 5-Cl CH2 4-Cl-Ph Q-l C(O)Me ~ 4-CF3 H CB2 ~ 0-2 Me : 4-Cl H CH2 H Q-2 Me ~, 35 . '.
: .
:' ' . .

, ' '' ' ' - - '. :: ~ . . '. . . . : . , ', ' ' . . :

x~ 49 Rl R2 A B Q Y
.
4-Br H CH2 H 0-2 Me 4-CF3 H CH2 H Q-2 C(O)Me 4-Cl H CH2 H Q-2 C(O)Me 4-Br H CH2 H Q-2 C(O)Me 4-CF3 H CH2 C02Me Q-2 Me . .
4-Cl H CH2 C02Me 0-2 Me 4-Br H CH2 2 Q-2 Me 4-CF3 H CH2 C02Me Q-2 C~O)Me 4-Cl H CH2 C02Me Q-2 C~O)Me 4-Br H CH2 C2Me Q-2 C~O)Me .~ 4-CF3 H CH2 C02Me Q-2 C0 Me ~ 4-Cl H CH2 C02Me Q-2 C2Me ~ 4-Br H CH2 C02Me Q-2 C2Me 4-CF3 4-F CH2 H Q-2 Me :
4-C1 4-F CH2 H Q-2 Me ~ 4-Br 4-F CH2 H Q-2 Me .; 4-CF3 4-F CB2 H Q-2 C~O)Me , 4 Cl 4-F CH2 H 9-2 C(O)Me 4-Br 4-F CH2 H Q-2 C(O)Me :
: 25 4-CF3 4-F CH2 C02Me Q-2 C2Me .` 4-C1 4-F CH2 C02Me Q-2 C02Me `.~ 4-Br 4-F CH2 CO2Me Q-2 C02Me . 4-CF3 4-F CH2 C02~e Q-2 C~O)Me ;.
, 4-C1 4 F CH C2Me Q-2 Ac - 30 9-Br 4-F C~2 C02Me Q-2 Ac .
. 4-CF3 H CH2 H a-3 Me 4-Cl H CH2 H o_3 Me 4-Br H CH2 ~ Q~3 Ac `:~ ,1 ,~. . :

. : , .` "' .
' :.
' ' .'~,:.

.: .. . . - . . . .. . . . .

Rl R2 ~ B Q y 4-CF3 HCH2 H Q-3 C(O)Me 4-Cl HC~2 H Q-3 C02Me 4-Br HCB2 H- 0-3 C2Me 4-CF 5-ClCH2 H Q-3 Me 4-C1 5-ClCH2 H Q-3 Me ~` 4-Br 5-ClCH2 H Q-3 C(O)Me 4-CF3 5-ClCH2 ~ Q-3 C(O)Me 4-Cl S-ClCH2 H Q-3 C0zMe 4-Br 5-ClCH2 H Q-3 2 4-CF3 HCH2 C02Me Q~3 Me ~ 4-Cl HCH2 C02Me g~3 Me :'. 4-Br HCH2 C02Me g-3 C(O)Me 4-CF3 HCH2 C02Me Q-3 C(O~Me ~ 4-Cl HCH2 C02Me Q-3 C~O)Me ;~ 20 4-Br HCH2 C02Me Q-3 C(O)Me , 4-CF3 HCH2 C02Me Q-3 C02Me , 4-Cl XCH2 C02Me Q-3 C2Me ., 4-Br HCH2 C02Me U-3 C0 Me .~ 4-CF3 5-ClCH2 C02Me. Q-3 Me .~ 25 4-C1 5-ClCH2 C02Me ~3 Me ~ 4-Br . 2 C02Me Q-3 Me .~. 4-CF3 5-ClCH2 C02Me Q-3 C(O)Me . 4-Cl S-ClCH2 C02Me Q-3 C(O)Me 4-Br 5-Cl CH2 C02Me Q-3 C(O)Me : 30 4-CF3 HCH2 H Q-5 C(O)Me 4-Cl HCH2 H Q-5 C(O)Me 4-9r ~CH2 H Q-5 C(O)Me .~ 4-CF3 HCH2 H Q-5 C2Me : :

: ' .
,,, . .
., X~ 4-~) -9-Cl H CH2 H Q-5 2 : 4-Br H CH2 H Q-S C02~e 4-CF3 5-Cl CH2 C02Me Q-5 C~O)Me 4-C1 5-Cl CH2 C02Me Q-5 C(O)Me 4-Br 5-Cl CH2 C02Me Q-5 C(O)Me 4-CF3 5-Cl CH2 C02Me Q-5 CO Me 4-C1 5-Cl CH2 C02Me Q-5 CO Me 4-Br 5-Cl C~2 C02Me Q~5 C02Me ~-CF3 5-C1 2 Q-5 C(O)Me : 15 4-C1 5-C1 2 Q-5 C(03Me 4-Br 5-ClCH2 Me 0-5 C(O)Me ~ 4-CF3 H CH2 H 0_7 C02Me .: 4-Cl H CH2 H Q 2 4-Br H CH2 H Q-7 C02Me 4-CF3 5-ClCH2 H Q-7 C(O)Me 4-C1 5-ClCH2 H Q-7 C(O)Me . 4-Br 5-ClCH2 H Q-7 C(O)Me :; 4-CF3 5-Cl CH2 C02Me 0-7 C02Me ~ -: 4-C1 5-Cl CH2 C02Me Q-7 C2Me : 25 4-Br 5-Cl CH2 C02Me Q-7 C2Me : 4-CF3 5-Cl CH2 C02Me Q-7 C(O)Me ,l'r. .;
i, 4~C1 5-Cl CH2 C02Me Q-7 C(OtMe 4-Br 5-Cl CH2 C02Me Q-7 C(O)Me - 4-CF3 H O H Q-l Me :
4-Cl H O H Q-l C(O)Me 4-Br H O H Q-l C02Me 4-CF3 H O Me Q-l Me 4-Cl H O Me Q-l C(O)Me 4-Br H O Me Q-l C02Me ~j ' ' 4 ~

Rl R2 A 8 0 Y
.; _.
4-CF3 5-Cl O H Q-l Me 4-C1 5-Cl O H Q-l C(O)Me 4-Br 5-Cl O H Q-l CO2Me 4-CF3 ~ o ~ Q-2 Me ~-Cl ~ O H Q-2 C(O)Me 4-Br H O H Q-2 CO2Me 4-CF3 H O ~ Q-2 Me 4-Cl ~ o H Q-2 C(O)Me 4-Br H O H Q-2 C2Me 4-CF3 H O H Q-3 Me lS 4-Cl ~ O H Q-3 C(O)Me 4-8r H O H Q-3 CO2Me ~: 4-CF3 H O H Q-3 Me 4-Cl H O H Q-3 C(O)Me 4-8r H O H Q-3 CO2Me . 4-CF3 H O H Q-5 Me ,. 20 4-Cl H O H Q-5 C(O)Me 4-Br H O H Q-5 CO2Me 4-OE 3 H O H Q-5 Me ; 4-Cl H O H Q-5 C(O)Me ~ 4-Br H O H Q-5 CO2~e ~ 25 4-CF3 H S H Q-l ~e :~ 4-Cl H S ~ Q-l C(O)Me 4-Br H S H Q-l CO2Me `/ , 4-CF3 H S 2 Q-l Me 4-Cl H S CO2Me Q-l C(O)Me 4-Br H S C2Me Q-l C2Me 4-CF3 H S H Q-2 Me 4-Cl H S H Q-2 C(O)Me 4-Br H S H Q-2 CO2Me 4-CF3 H S CO2Me Q-2 Me . . .

, 35 :, :
., ~ . ..... ... .

, :

- .

_~ 2~.2'~

Rl R2 A B Q Y
.
4-Cl H S CO2Me Q-2 C(O)Me . 4-Br H S CO2Me Q-2 CO Me 4-CF3 H S H Q-3 Me 0 4-Cl H S H Q-3 C(O)Me 4-Br H S H Q-3 CO2Me 4-CF3 H S CO2Me Q-3 Me 4-Cl H S CO2Me Q-3 C(O)Me 4-Br H S CO2Me Q-3 C2Me .~ 4-CF3 H S H Q-5 Me : 15 4-Cl H S H Q-5 C(O)Me : : 4-Br H S H Q-5 CO2Me . 4-CF3 H S CO2Me Q~5 Me 4-Cl H S CO2Me Q-5 C(O)Me - 4-Br H S CO2Me Q-5 C2Me !`:
4-CF3 H S H Q-7 Me ~ 4-Cl H S H Q-7 C(O)Me ~. .
`~ 4-Br H S H 0-7 CO2Me ~ 4-CF HCH H Q-l N(Me)CO Et .: 3 2 2 4-Cl HCH H Q-l N(Me)CO Et ~; 2 2 -:
'r' 25 4-Br HCH H Q-l N(Me)CO Et 2 2 .
;~ 4-CF HCH H Q-l N(Me)CO nBu . 3 2 2 :
. 4-Cl HCH H Q-l N(Me)CO nBu ,~, 2 2 ~; 4-Br HCH H Q-l N(Me)CO ~Bu : 30 2 2 :~' .. . :
~, .

., : ~ ' ~ ..`L ~ ~9 Table 12 Rl R2 .A B Q J
' ~
4-CF3 5-ClC~2 H Q-l N(iPr)CO2Et 4-C1 5-C1 2 Q-l N~iPr)C02Et : 10 4-Br 5-ClCH2 H Q-l N(iPr)C02Et 4-CF3 5-ClCH2 H 0-1 N(Et)CO2Et ~ ' :
4-C1 5-ClCH2 H 0-1 N(Et)C02Et 4-Br 5-ClCH2 H Q-l N(Et)C02Et ::
4-CF3 ~ CH2 CO2Me Q-l N(Et)CO2Et 4-Cl H CH2 C02Me 0-1 N(Et)C02Et 4-Br H CH2 C02Me Q-l N(Et)CO2Et .~ 4-CF3 H CH2 CO2Me Q-l N(iPr)CO2Et 4-Cl H CH2 CO2Me Q-l N(iPr)CO2Et 4-Br H CH2 C2Me Q-l N(iPr)CO2Et 4-CF3 5-Cl CH2 C2Me Q-l N(iPr)CO2Et ~ :
4-C1 5-Cl CH2 C2Me Q-l N(iPr3CO2Et 4-Br 5-Cl CH2 C2Me Q-l NliPr)CO2Et ~ 4-CF3 5-Cl CH2 CO2Me Q-l N(Me)CO2nHex .~ 4-C1 5-Cl CH2 C02Me Q-l N(Me)CO2nHex :`) 25 4-Br 5-Cl CH2 C02Me Q-l N(Me)CO2nHex .~' 4-CF3 5-Cl ~H2 Ph Q-l N(Me)C02Et 4-C1 5-C1 2 Q-l N(Me)co2Et 4-Br 5-Cl CH2 Ph Q-l N(Me)CO2Et 4-CF3 H CH2 ~ Q-3 N(Me)CO2Et 4-Cl H CH2 H Q-3 N(Me)C02Et 4-Br H CH2 H Q-3 N(Me)CO2Et 4-cr3 H CH2 H 0-3 N(Me)C02~Bu :;'--.
4-Cl H CH2 H Q-3 N(Me)C02nBu ,, -.
.
: .

r~ 4 ~3 :

Rl R2A B Q J

4-Br HCH2 H Q-3 N(Me)CO2nBu 4-CF3 5-C12 , O-3 N(ipr)co2Et 4-C1 5-ClCH2 H Q-3 N(iPr)CO2Et 4-Br 5-C12 Q~3 N(~Pr)CO2Et : 4-CF3 5-ClCH2 H Q-3 N(Et)CO2Et 4-C1 5-ClCH2 H Q-3 N(Et)CO2Et 4-Br 5-ClCH2 H 0-3 N(Et)CO2Et 4-CF3 HCH2 CO2Me Q~3 N(Et~CO Et 4-Cl HCH2 CO2Me Q~3 N(Et)CO2Et ~.
4-Br HCH2 CO2Me Q~3 N(Et)CO2Et 4-CF3 2 C2Me Q-3 N(iPr)CO2Et 4-Cl HCH2 CO2Me Q~3 N(iPr)CO2Et 4-Br HCH2 C2Me 0-3 N(iPr)CO2Et 4-CF3 5-ClCH2 C2Me Q-3 N(iPr)CO2Et .~ 4-C1 5-ClCH2 CO2Me Q_3 N(iPr)CO2Et ~ 4-Br 5-ClC~2 CO2Me Q~3 N(iPr)CO2Et .~ 4-CF3 5-ClCH2 CO2Me Q~3 N(Me)CO2nHex 4-C1 5-ClCH2 CO2Me Q~3 N(Me)CO2nHex 4-Br 5-ClCH2 CO2Me ~3 N(Me)CO2nHex 4-CF3 5-C12 Q-3 N(Me)co2Et 4-C1 5-C12 Q~3 ~lMe)co2Et . 4-~3r 5-ClCH2 Ph Q-3 N(Me)CO2Et 4-CF3 H' CH2 H Q-4 N(Me)co2Et 4-CI NCH2 H 0-4 N(Mr)co2Et ,. , ~:.
~ .

.. ' .
,, ' .

4 ~3 Rl R2 A B Q J
4-Br H CH2 H Q-4 N(Me)CO2Et 4-CF3 H CH2 H o_4 N(Me)CO2nBu 4-Cl H CH2 H Q_4 N(Me)co2nBu ~.
4-Br H CH2 H Q-4 N(Me)CO2nBu 4-CF3 5-Cl, CH2 H Q-4 N(iPr)CO2Et 4-C1 5-Cl CH2 H Q_4 N(iPr)CO2Et : 4-~r 5-Cl C~2 H Q_4 N(iPr)C02Et 4-CF3 5-Cl CH2 H Q_4 ~(Et)CO2Et ~ 4-C1 5-Cl CH2 H Q-4 N(Et)co2Et : 15 4-Br 5-Cl CH2 H Q-4 N(Et)CO2Et 4-CF3 H CH2 CO2Me Q-4 N(Et)CO
4-Cl H CH2 CO2Me Q-4 N(Et)CO2Et - 4-Br H CH2 C2Me 0-4 N(Et)CO2Et 4-CF3 H CH2 CO2Me 0-4 N(iPr)CO2Et 4-Cl H CH2 CO2Me Q_4 N(iPr)CO2Et , 4-Br N C~2 CO2Me Q-4 N(iPr)CO2Et 4-CF3 5-Cl C~2 co2Me Q-4 N(iPr)CO2Et 4-C1 5-Cl CH2 co2Me Q-4 N(ipr)co2Et ~ 4-Br 5-Cl CH2 CO2Me- Q-4 N(iPr)CO2Et -'~ -:~ 25 4-CF3 5-Cl CH2 CO2Me Q-4 N(Me)co2nHex 4-Cl C 2 CO2Me Q-4 N(Me)co2nHex i 4-Br 5-Cl CH2 CO2Me Q-4 N(Me)CO2nHex ,' 4-CF3 5-Cl CH2 Ph Q-4 N(Me)CO2Et 4-C1 5-Cl CH2 Ph Q-4 N(Me)CO2Et 4-Br 5-Cl CH2 Ph Q-4 N(Me)CO2Et 4-CE3 H CH2 N - Q-5 N(Me)CO2Et .` 4-C1 ~ 2 . Q-5 N(Me)CO2Et 4-Br H CH2 H Q-5 N(Me)CO2Et . 35 ' :' "

.,, : '-: ~ :
' ' , :

~ L~ 9 Rl R2 A B Q J
4-CF3 H CH2 H Q-5 N(Me)co2nBu 4-Cl N CH2 H Q-5 N(Me)CO2nBu 4-Br H CH2 H Q-5 N(Me)CO2nBu . 4-CF 5-Cl CH2 H Q-5 N(iPr)CO2Et 4-C1 5-Cl CH2 H Q-5 N(iPr)CO2Et ~-4-Br 5-Cl CH2 H Q-5 N(iPr)CO2Et ~: 4-CF3 5-Cl CH2 H Q-5 N(Et)CO2Et - 4-C1 5-Cl CH2 H 0-5 N(Et)CO2Et 4-Br 5-Cl CH2 H Q-5 N(Et)CO2Et 4-CF3 H CH2 C02Me Q-5 N(Et)CO2Et 4-Cl H CH2 C02Me ~5 N(Et)C02Et 4-Br H CH2 CO2Me Q~5 N(Et)CO2Et 4-CF3 ~ CH2 C02Me ~5 N(iPr)C02Et 4-Cl H CH2 CO2Me Q~5 N(iPr)C02Et 4-Br H CH2 C02Me Q~5 N(iPr)C02Et 4-CF3 5-Cl CH2 C02Me Q~5 N(iPr)C02Et ~i 4-C1 5-Cl CH2 C02Me Q~5 N(iPr)CO2Et 4-Br 5-Cl CH2 CO2M~ ~5 N(iPr)CO2Et 4-CF3 5-Cl CH2 CO2Me ~5 N(Me)C02nHe~
4-C1 5-Cl CH2 CO2Me Q~5 N(Me)CO2nHex 4-Br 5-Cl CH2 CO2Me ~5 N(Me)CO2nHe~
4-CF3 5-C1 2 Q-5 N~Me)CO2Et 4-C1 5-Cl CH2 Ph Q_5 N~Me)CO2Et ::
4-Br 5-Cl CH2 Ph Q-5 N(Me)CO2Et :~
4-CF3 H CH2 H Q-l N(Me)SO2Ph 4-Cl H CH2 H Q-l N(Me)S02Ph .
4-Br H CH2 H Q-l N(Me)S02Ph . 4-CF3 H CH2 C02Me Q-l N(Me)SO2Ph `

~. '.': ' .

:"
.' ' .

,:
:

4-Cl H CH2 C02Me Q-l N(Me)S02Ph :~ 4-Br H CH2 C02Me 0-1 N(Me)S02Ph , 4-CF3 ~ CH2 Ph Q-l N(Me)S02Ph 4-Cl H CH2 Ph Q-l N(Me)S02Ph 4-8r H CH2 Ph 0-1 N(Me)S02Ph ~ 4-CF3 H CH2 Me Q-l N(Me)S02Ph : 4-Cl H CH2 Me Q-l N(Me)S02Ph 4-Pr H CH2 Me Q-l N(Me1so2ph 4-CF3 S-Cl CH2 H Q-l N(Me)S02Me : 15 4 -Cl 5-Cl CH2 H Q-l N(Me)so2Me 4-Br 5-Cl CH2 H Q-l N(Me)S02Me , . 4-CF3 5-Cl CH2 C02Me Q-l N(Me)S02Me 4-C1 5-Cl CH2 C02Me 0-1 N(Me)S02Me - 4-Br S-Cl CH2 C02Me Q-l N(Me)S02Me :~ 20 4-CF3 5-Cl CH2 Ph Q-l N(Me)S02Me 4-C1 5-Cl CH2 Ph Q-l N(Me)so2Me 4-~r 5-Cl CH2 Ph Q-l N(Me)S02Me ; 4-CF3 S-Me CH2 H Q-l N(Me)S02Me 4-C1 5-Me C~2 H Q-l N(Me)S02Me 4-Br 5-Me CH2 H Q-l N(Me)S02Me . - 4-CF3 5-Me CH2 C02Me Q-l N(Me)S02Ph-4-Me 4-C1 5-Me CH2 C02Me Q-l N(Me)S02Ph-4-Me 4-Br 5-Me CH2 2 Q-l N(Me)so2ph-4-Me ~, 4-CF3 H CH2 H Q-2 N(Me)S02Ph 4-Cl H CH2 H Q-2 N(Me)S02Ph 4-Br H CH2 H Q-2 N(Me)S02Ph 4-CF3 H CH2 C02Me Q-2 N(Me)S02Ph `~ 4-Cl H CH2 C02Me Q-2 N(Me)S02Ph G' . .
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4-Br H CH2 C2Me Q-2 N(Me)SO2Ph ~-CF3 HCH2 Ph Q-2 N(Me)so2ph 4-Cl HCH2 Ph O-2 N(Me)SO2Ph 4-Br HCH2 Ph Q-2 N(Me)SO2Ph 4-CF3 HCH2 Me Q-2 N(Me)SO2Ph 4-Cl HCH2 Me Q-2 N(Me)SO2Ph 4-Br HCH2 Me 0-2 N(Me)SO2Ph 4-CF3 HCH2 H 0-3 NSMe)SO2Ph . ~. -4-Cl HCH2 H Q-3 N(Me)SO2ph : 15 4-Br HCH2 H Q-3 N(Me)SO2Ph ~ r 4-CF3 H CH2 CO2Me Q~3 N(Me)SO2Ph ~ . .
4-Cl H CH2 CO2Me Q-3 N(Me)SO2Ph 4-Br 2 CO2Me Q-3 N(Me)SO2Ph ,` 4-CF3 HCH2 Ph Q-3 N(Me)5O2Ph 4-C1 H 2 Q-3 N(Me)SO2Ph 4-Br HCH2 Ph Q-3 N(Me)SO2Ph 4-CF3 HCH2 Me Q-3 N(Me)SO2Ph 4-Cl HCHz Me Q-3 N(Me)SO2Ph 4-Br BCH2 Me Q-3 N(Me)SO2Ph 4-CF3 5-ClCH2 H Q-3 N(Me)SO2Me 4-Cl S-ClCH2 H Q-3 N(Me)SO2Me 4-Br 5-C1 2 Q~3 N(Me)so2Me 4-CF3 5-ClCH2 CO2Me Q-3 N(Me)SO2Me 4-C1 5-ClCH2 CO2Me Q-3 N~Me)SO2Me ~ 30 4 Br 5-ClCH2 CO2Me 0-3 N(Me)SO2Me ,:
;,, 4-CF3 5-C1 2 9~3 N(Me)so2Me 4-Cl S-ClCH2 Ph o_3 N(Me)SO2Me ~:.
4-Br 5-C1 2 ~3 N(Me)SO2Me "j :

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4-CF3 5-Me CH H Q-3 N(Me)SO2Me 4-C1 5-Me CH2 H Q-3 N(Me)SO2Me 4-Br 5-Me CH2 H Q-3 N(Me)SO2Me . 4-CF 5-Me CH2 CO2Me Q-3 N~Me)so2ph-4-Me 4-C1 5-Me CH2 CO2Me Q-3 N(Me)so2ph-4-Me 4-Br 5-Me CH2 CO2Me Q~3 N(Me)SO2Ph-4-Me 4-CF3 H CH2 H o_4 N(Me)SO2Ph 4-Cl H CH2 H Q_4 N(Me)so2ph 4-Br H CH2 H Q-4 N(Me)SO2Ph 4-CF3 H CH2 co2Me Q-4 N(Me)SO2Ph 4-Cl H CH2 CO2Me Q-4 N(Me)SO2Ph 4-Br H CH2 CO2Me 0-4 N(Me)SO2Ph 4-CF3 H CH2 Ph Q-4 N(Me)SO2Ph ~- 4-Cl H CH2 Ph Q-4 N(Me)SO2Ph 4-Br H CH2 Ph Q-4 N(Me)SO2Ph ~;: 4-CF3 H CH2 Me Q-4 N(Me)SO2ph 4-Cl H CH2 Me Q-4 N(Me)SO2Ph 4-9r H CH2 Me Q-4 N(Me)SO2Ph . 4-CF3 5-Cl CH2 H Q_4 N(Me)so2Me ,~ 25 4-C1 5-Cl CH2 H Q-4 N(Me)SO2Me 4-Br 5-Cl CH2 H Q_4 N(Me)SO2Me :
4-CF3 5-Cl CH2 CO2Me Q-4 N(Me)SO2Me 4-C1 5 Cl CH2 CO2Me Q-4 N(Me)SO2Me 4-Br 5-Cl CH2 CO2Me Q-4 N(Me)so2Me 4-CF3 5-C1 2 Q-4 N(Me)SO2Me -- 4-C1 5-C1 2 Q-4 N(Me)so2Me ::.
4-9r 5-C1 2 Q~4 N(Me)so2Me 4-CF3 5-Me CH2 N Q-4 N(Me)SO2Me -`

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4-C1 5-Me CH2 H 0-4 N(Me)SO2Me 4-Br 5-Me CH2 H Q-4 N(Me)so2Me 4-CF3 5-Me 2 CO2Me Q-4 N~Me)so2ph 4-C1 5-Me C~2 CO2Me 0-4 N(Me)SO2Ph-4-Me 4-Br 5-Me C~2 CO2Me Q-4 N(Me)SO2Ph-4-Ne :
4-CF3 H C~2 H Q-5 N(Me)SO2Ph ; 4-Cl H CH2 H 0-5 N(Me)SO2Ph : 4-Br H CH2 H Q-5 ~(Me)SO2Ph 4-CF3 H CH2 CO2Me 0-5 N(Me)SO2Ph 4-Cl H CH2 CO2Me ~5 N(Me)so2ph H 4-Br H CH2 CO2Me 0-5 N(Me)SO2Ph 4-CF3 H CH2 Ph Q-5 N(Me)SO2Ph 4-Cl H CH2 Ph 0-5 N(Me)SO2ph ~ 4-Br H CH2 Ph Q-5 N(Me)SO2Ph ; 20 4-CF3 H CH2 Me Q-5 N(Me)SO2Ph `. 4-Cl H CH2 Me Q-5 N(Me)SO2Ph 4-Br H CHz Me Q-5 N(Me)SO2Ph . 4-CF3 5-Cl CN2 H Q-5 N(Me)SO2Me i~ 4-C1 5-Cl C~2 H Q-5 N(Me)SO2Me 4-Br 5-Cl CH2 H Q-5 N(Me)SO2Me .~ 4-CF3 5-Cl CH2 CO2Me Q~5 N(Me)SO2Me .~ 4-Cl 5-Cl CH2 CO2Me Q~5 N(Me)SO2Me 4-Br 5-Cl CH2 CO2Me Q~5 N(Me)SO2Me .. 4-CF3 5-Cl CH2 Ph Q-5 N(Me)SO2Me 4-C1 5-C1 2 Q-5 N(Me)so2Me `~ 4-Br 5-Cl CH2 Ph Q-5 N(Me)SO2Me 4-CF3 5-Me CH2 H Q-5 N(Me)SO2Me ~, 4-C1 5-Me CH2 H Q-5 N(Me)so2Me ., ,:

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4-Br 5-Me CH2 H Q-5 N(Me)SO2Me 4-CF3 5-Me CH2 C2Me 0-5 N(Me)SO2Ph-4-Me 4-C1 5-Me C~2 C02Me ~5 N(Me)SO2Ph-4-Me 4-Br 5-Me CH2 CO2Me Q~5 N(Me)SO2Ph-4-Me 4-CF3 H CH2 H Q-7 N(Me)SO2Ph 4-Cl H CH2 H Q_7 N(Me)SO2Ph 4-Br H CH2 H Q-7 N(Me)SO2Ph 4-CF3 H CH2 CO2Me Q_7 N(Me)SO2Ph 4-Cl ~ C~2 CO2Me Q-7 N(Me)so2ph 4-~3r H CH2 CO2Me Q_7 N(Me)so2ph 4-CF3 H CH2 Ph Q_7 N(Me)so2ph 4-Cl H CH2 Ph Q_7 N(Me)SO2Ph q-~r H CH2 Ph Q_7 N(Me)502Ph 4-~F3 H CH2 Me Q-7 N~Me)SO2Ph 4-Cl H CH2 Me 0-7 N(Me)SO2Ph 4-8r H CH2 Me Q_7 N(Me)SO2Ph :
4-CF3 5-Cl CH2 H Q-7 N(Me)SO2Me . 4-C1 5-Cl CH2 H Q_7 N(Me)SO2Me ::.
4-9r 5-Cl CH2 H Q_7 N(Me)so2Me 4-CF3 5-Cl CH2 CO2Me Q-7 N(Me)so2Me :, 4-C1 5-Cl CH2 CO2Me Q-7 N(Me)SO2Me 4-~r 5-Cl CH2 CO2Me Q-7 N(Me)SO2Me 4-CF3 5-C1 2 Q-7 N(Me)so2Me 4-Cl S-Cl 2 Q-7 N(Me)SO2Me: :
4-Br 5-C1 2 Q-7 N(Me)SO2Me 4-CF3 5-Me CH2 H Q-7 N(Me)SO2Me 4-Cl S-~e CH2 H Q_7 N(Me)SO2Me 4-~r 5~e 2 Q-7 N(Me)so2Me `.:

2~-$Y; ~9 118 -' 4-CF3 5-Me CH2 C02Me Q-7 NtMe)S02Ph-4-Me 4-C1 5-Me CH2 C02Me 0-7 N(Me)so2ph-4-Me 4-Br 5-Me CH2 C02Me Q-7 N~Me)S02Ph-4-Me : 4-CF3 H CH2 B Q-l C02Me : 10 4-Cl H CH2 H 0-1 C02Me 4-Br H CH2 H Q-l C02Me . 4-CF3 H CH2 C02Me Q-l C02Me q-Cl H CH2 C2Me Q-l C02Me 4-Br H CH2 C2Me Q-l C2Me 1~ 4-CF3 H CH2 Ph Q-l COzMe 4-Cl H CH2 Ph Q-l C02Me , 4-Br H CH2 Ph Q-l C02Me 4-CF3 H CHz Me 0-1 C02Et ~;~
4-Cl H 2 Q-l C2Et 4-Br H CH2 Me 0-1 C2Et 4-CF3 5-Cl CB2 H Q-l C02nPr ' 4-C1 5-Cl C~2 ~ Q-l C02nPr ~ 4-Br 5-Cl CH2 H Q-l C02nPr ., 4-CF3 5-Cl CH2 C02Me Q-l C02nPr ,~ 25 4-C1 5-Cl CH2 C02Me Q-l C02nPr ;
.'; 4-Br 5-Cl CH2 2 0-1 C02nPr :
4-CF3 5-C1 2 Q-l C2CH2CH2Et :` 4-C1 5-C1 2 Q-l C02CH2cH20Et 4-Br 5-Cl CH2 Ph Q-l C02CH2CH20Et . .
. 30 4-CF3 5-Me CH2 H 2 2 4-C1 5-Me CH2 H Q-l C02CH2Ph , 4-Br 5-Me CH2 H Q-l C02CH2Ph 4-CF3 5-Me C~2 C02Me Q-l C02CH2Ph ;

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4-C1 5-Me C82 C2Me Q-l C02CH2Ph 4-Br 5-~e C~2 2 Q-l C02CH2Ph 4-CF3 H CH2 H Q-l C02n~u : 4-Cl H CH2 B Q-l C02nBu 4-Br H CH2 H Q-l C02nBu , 4-CF3 H CH2 C2Me Q-l C02nBu : 4-Cl H CH2 C02Me Q-l ~C02DBu 4-Br H CH2 C02Me Q-l C02nBu 4-CF3 H CH2 Ph Q-l C02nBu 4-Cl H CH2 Ph Q-l C02nBu . 4-Br H CH2 Ph Q-l C02nBu : 4-CF3 H CH2 Me Q-l C02nBu 4-Cl H CH2 Me Q-l C02nBu 4-Br H CH2 Me Q-l C02nBu .~.
4-CF3 5-Cl CH2 H Q-l C02nBu ; 4-C1 5-Cl CH H Q-l C02DBu 4-Br 5-Cl CH2 H Q-l C02nBu 4-CF3 5-ClCH2 C02Me Q-l C02nBu 4-C1 5-ClCH2 C02Me Q-l C02n8u - 25 4-Br 5-ClCH2 C02Me Q-l C02nBu 4-CF3 5-C1 2 Q-l C02nBu 4-CI 5-C1 2 Q-l C02nBu -~ 4-Br S-Cl 2 Q-l C02nBu 4-CF3 5-Me CH2 H Q-l C02nBu .. 30 4-C1 5-Me CH2 H Q-l C02nBu `'! 4-Br 5-Me CH2 H Q-l C02nBu ,~ 4-CF3 5-~e CN2 C02Me Q-l C02nBu - 4-C1 5-Me CH2 C02Me Q-l CO nBu . . .

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, 4-Br 5-Me CH2 2 Q-l CO2nBu 4-CF3 H CH2 H Q-3 C2Me : 4-Cl H CH2 H g-3 C2Me 4-Br H CH2 H Q-3 CO2Me ..
4-CF3 H CH~ CO2Me Q-3 CO2Me .:
4-Cl H C~2 CO2~e Q-3 COzMe 4-Br H C~2 CO2Me 0-3 CO2Me 4-CF3 H CH2 Ph Q-3 C2Me 4-Cl H CH2 Ph Q-3 CO2Me 4-Br B CH2 Ph Q-3 C2Me 4-CF3 H CH2 Me Q-3 C2Et 4-Cl H CH2 Me Q-3 C2Et 4-Br H CH2 Me Q-3 CO2Et .:
4-CF3 5-Cl CH2 H Q-3 CO2nPr :
4-Cl 5-Cl C~2 H Q-3 CO2nPr 4-Br 5-Cl CH2 H Q-3 CO2nPr 4-CF3 5-Cl CH2 CO2Me Q-3 CO nPr 4-C1 5-ClCH2 CO2Me Q-3 CO2nPr 4-Br 5-ClCH2 CO2Me 0-3 CO2nPr 4-CF3 5-Cl 2 Q-3 CO2CH2CH2OEt q-Cl 5-Cl 2 Q-3 CO2CH2cH2OEt 4-Br 5-Cl 2 Q-3C2CH2CH2Et 4-CF3 5-MeCH2 H Q-3CO2CH2Ph 4-C1 5-MeCH2 H Q-3CO2CH2Ph 4-Br 5-MeCH2 H 0 2 2 4-CF3 5-MeCH2 CO2Me Q-3 CO2CH2Ph 4-C1 5-Me CH2 CO2Me Q-3 CO CH Ph 4-Br 5-MeCH2 CO2Me Q-3 CO2CH2Ph ,, ~ , .
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, . _ _ _ 4-CF3 H .CH2 H Q-3 C02nBu : 4-Cl H CH2 H Q-3 C02nBu 4-Br H CH2 H 0-3 C02nBu -CF3 H CH2 C02Me Q-3 C02nBu 4-Cl H CH2 C02Me 0-3 C02nBu 4-Br H CH2 C02Me Q-3 C02n~u 4-CF3 H CH2 Ph 0-3 C02nBu 4-Cl H CH2 Ph Q-3 C02nBu 4-Br H CH2 Ph Q-3 C02nBu 4-CF3 H C~2 Me 0-3 C02nBu 4-Cl H C~2 Me 0-3 C02nBu 4-Br H CH2 Me 0-3 C02nBu g-CF3 5-ClCH2 H 0-3 C02nBu 4-C1 5-ClCH2 H 0-3 C02nBu : 20 4-Br 5-ClCH2 H Q-3 C02nBu 4-CF3 5-ClCH2 C02Me 0-3 CO nBu 4-C1 5-ClCH2 C02Me 0-3 Co2nBu ~, 4-Br 5-ClCH2 C02Me Q-3 C02n~u -~ 4-CF3 5-C12 Q-3 C02nBu -:~ 25 4-Cl S-Cl2 0-3 C02nBu i 4-Br 5-C12 0-3 C02nBu 4-CF3 5-Me2 H Q-3 C02nBu ii 4-C1 5-MeCH2 H Q-3 C02nBu . 4-Br 5-Me 2 H Q-3 C02nBu 4-CF3 5-MeC~2 C02Me Q-3 CO nBu 4-C1 5-MeCH2 C02Me ~3 C02nBu 4-Br 5-MeCH2 C02Me 0-3 C02DBu .~ 4-CF3 2 Q 2 .
i, 35 , ' .

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4-Cl H CH2 H Q-4 C02Me 4-Br H CH2 H Q-4 C2Me ~ 4-CF3 H CH2 C02Me 0-4 C02Me : 4-Cl H CH2 C02Me, Q-4 C02Me 4-Br H C~2 C02Ne Q-4 C02Me 4 CF3 H CH2 Ph Q-4 C2Me 4-Cl H CH2 Ph Q-4 C02Me 4-Br H CH2 Ph Q-4 C2Me : 4-CF3 H CH2 Me ~4 C02Et 4-Cl H C82 Me Q-4 C02Et 4-Br H CH2 Me Q 2 4-CF3 5-Cl CH2 H Q-4 C02DPr 4-C1 5-Cl CH2 H Q-4 C02nPr :~
4-Br 5-Cl CH2 H Q-4 C02nPr 4-CF3 5-C1 2 2 QC02nPr `~
4-C1 5-C1 2 2 QC02nPr . 4-Br 5-ClCH2 C02Me Q-4C02nPr 4-C1 5-C1 2 Q-4 C2CH2CH2Et . 25 4-Br 5-C1 2 Q-4 C02CHzCH20Et ., 4-CF3 5-Me CH2 H Q 2 2 ,. 4-C1 5-MeCH2 H Q-4 C02CH2Ph :~
4-Br 5-MeCH2 H Q-4 C02CH2Ph } 4-CF3 5-MeCH2 C02Me Q-4 C02C~2Ph ' 30 4-C1 5-MeCH2 C02Me Q-4 COzCH2Ph : 4-~r 5-MeC82 C02Me Q-4 CO CH Ph ; 4-CF3 H CH2 ~ Q~4 C02DBu 4-Cl H CH2 H Q-4 C02nBu ::

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4-Br H CH2 H Q-4 C02nBu 4-CF3 HCH2 C02Me 0-4 C02nBu q-Cl HCH2 C02Me 0-4 C02nBu 4-Br ~CH2 C02Me Q-4 C02nBu 4-~F3H CH2 Ph Q-4 C02nBu 4-Cl HCH2 Ph Q-4 C02nBu 4-Br 2 Q-4 C02nBu 4-CF3 HCH2 Me Q-4 C02n8u 4-Cl HCH2 Me Q-4 C02nBu 4-~r H CH2 Me Q-4 C02nBu 4-CF3 S-ClCH2 H Q-4 C02nBu 4-C1 5-ClCH2 H Q-4 C02nBu : 4-Br 5-ClCH2 H Q-4 C02n8u : 4-CF3 5-ClCH2 C02Me 0-4 C02nBu : 20 4-C15-Cl CH2 C02Me Q-4 C02nBu 4-Br 5-ClCH2 C02Me g-4 C02nBu 4-CF3 5-C1 2 Q-4 C02nBu 4-C1 5-C1 2 Q-4 C02nBu ,, 4-Br 5-ClCH2 Ph Q-4 C02nBu ~; 25 4-CF35-Me CH2 H Q-4 C02nBu 4-C1 5-Me .CH2 H Q-4 C02nBu 4-Br S-MeCH2 H Q-4 CO~nBu 4-CF3 5-MeCH2 C02Me Q-4 C02nBu :
4-Cl S-MeCH2 C02Me Q-4 C02nBu -` 30 4-BrS-Me CH2 C02Me Q-4 C02nBu ::
' 4-CF3 HCH2 H Q-5 C02Me 4-Cl HCH2 H Q-S C2Me 4-Br HCH2 H Q-S C2Me ," .:
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2~ -9 : 124 . ~ . _ . _ 4-CF3 2 2 Q C2Me 4-Cl H CH2 C2Me O-S C2Me 4-Br H CH2 C02Me Q~S C02Me 4-CF3 ~CH2 Ph Q-5 C2Me 4-Cl HCH2 Ph 0-5 C02Me 4-Br HCH2 Ph Q~5C02Me 4-CF3 HCB2 Me Q-5 C2Et : 4-Cl ~CH2 Me Q~5C02Et : 4-Br HCH2 Me Q-5 2 4-CF3 5-ClCH2 H Q-5C02nPr 4-C1 5-ClCH2 H Q-5C02nPr `. 4-Br 5-ClCH2 H Q-5C02nPr 4-CF3 5-C12 2 Q C02nPr -~ 4-C1 5-C12 2 Q C02nPr . 20 4-Br 5-C12 2 Q C02nPr 4-CF3 5-ClCH2 Ph Q-5~02CH2CH20Et .i 4-C1 5-ClCH2 Ph Q-5C02CH2CH20Et 4-Br 5-ClCH2 Ph Q-5C2CH2CH2Et ~, 4-CF3 5-MeCH2 H Q-5C02CH2Ph ;~ 25 4-C1 5-MeCH2 H Q-5C02CH2Ph 4-Br 5-~eCH2 H 0-52 2 4-CF3 5-MeCH2 C02Me Q-52 2 . 4-C1 5-Me2 2 Q 5 C02CH2Ph 4-Br 5-Me2 2 Q 5 2 2 . 30 4-CF3 BCH2 H Q-5C02nBu 4-C1 2 QC02nBu :
4-Br HCHz H Q-5C02nBu : 4-CF3 HCH2 C02Me Q-5C02nBu ~, .~ , .
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2~ 3 Rl R2 A B O J
4-Cl H CH2 C02Me Q-5 C02nBu :. 4-Br H CH2 C02Me Q-5 C02nBu 4-CF3 H 2 g-5 C02nBu 4-Cl H CH2 Ph Q-5 C02nBu 4-Br H 2 Q-5 C02DBu 4-CF3 H CH2 Me Q-5 C02nBu 4-Cl H CHz Me Q-5 C02nBu 4-Br H CH2 Me 0-5 C02nBu ~ 4-CF3 5-Cl CH2 H Q-5 C02nBu : 15 4-C1 5-Cl CH2 H Q-5 C02nBu 4-8r 5-Cl CHz H Q-5 C02nBu 4-CF3 5-Cl CH2 C02Me Q-5 C02nBu ' 4-C1 5-Cl CH2 C02Me 0-5 C02nBu ; 4-Br 5-Cl CH2 C02Me Q-5 C02nBu '. 20 4-CF3 5-C1 2 Q-5 C02nBu 4-C1 5-Cl CH2 Ph Q-5 C02nBu 4-Br 5-Cl CH2 Ph Q-5 C02nBu 4-CF3 5-Me CH2 H Q-5 C02nBu 4-C1 5-Me CH2 H Q-5 C02nBu : 25 4-Br 5-Me CH2 H Q-5 C02nBU
. 4-CF3 5-Me CH2 C02Me Q-5 C02nBu - .
4-C1 5-Me CH2 C02Me 0-5 C02nBu `.; 4-Br 5-Me C~2 C02Me Q-5 C02nBu ~ !~-. , .
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B B H O
. 4-Cl H H O

4-Br X H O
: 4-C~3 H H O
~ 10 4-OCF2H H H O
.~ 4-CF3Cl H H O
4-CO2Me H H O
4-C02-i-Pr H H O
., 4-N02 H H O
- 15 4-SMe H H o 4-SO2Me H H O
4-CF2Cl H H O
.~ 4-OCF3 H H O
4-I H H o ' 4-Me H H O
3,4-CF2CF2O H H O
3,4-OCF2CF2 H H O
3,4-(Me)2CCH2O H O O
. 25 4-Cl H Me O
4-Br H Me O
'a 4-CF3 H Me O
4-SMe H Me O
.~ 4-OCF2H ~ Me O
.~......... 4-CF3 H Et O
4~C2i-Pr H Me O
., 4-Cl H allyl O
4-Br H allyl O
. 4-CF3 H allyl O
4-Cl H CH2Ph O
4-Br H CH2Ph O
4-CF3 H CH2Ph ~`' 4-CF3 H 4-F-CH2Ph O
4-SMe H 4-F-CH2Ph O

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, 4-CF3 B 4-F-CH2Ph O
4-CF3 H 4-Cl-C~12Ph O
4-NO H 4-Cl-CH2Ph O
4-OCF2H H Ph O
~ 4-OCF3 H Ph O
: 4-CF3 H Ph O
; 4-Cl H 4-Cl-Ph O
4-Br H 4-Cl-Ph O
: 4-OMe H 4-Cl-Ph O
4-CF3 H n-Bu O
4-Cl H n-Bu O
4-CF3 H (CB2)3Cl O
4-Cl H (CH2)3C1 4-Br H CH2CF3 O

4-SCF2H H CH20Me . 4-CF3 H CH20Et O
4-Cl H CH2CO2Me O
4-Br H CH2CO2Me O
4-OCF2H H CHzCN O
~, 25 4-OCF2CF2B H (CH2)2CN O
. 4-CF3 H (CH2)2CN O
;` 4-CF3 H tCH2)3CN O
4-CF3 H C2Me O
4-Cl ~ CO2Me O
: 3C 4-Br H C2Me O
: 4-F H C2Me O
4-CF2Cl H C2Me O
4-OCF3 H C2Me O

3,4-CF2CF20 H C2Me O
3,4-OCF2CF20 H COzMe O
3,4-~Me)2CCH20 H C2Me O
4-CF3 H C2~t O

~ . . ...

r~-~r, 4-Br 2 4-Cl H C2Et 4-CF3 H CO2H o 4-CF3 H C2Na 4-CF3 H C02Ph o 4-F H C02Ph o : 4-CF3 2 2 3 . 15 4-CF3 H CO2(CH2)Cl O
.. 4-CF3 2( 2)2 :~ 4-CF3 H CO2allyl O
4 CF3 H CO2CH2Ph O
i~ 20 4-CF3 2 2 O
4-CF3 H C(O)NH2 O
4-Cl H C(O)NH2 O
~ 4-Br H C(O)NHMe O
.~, 4-oCF3 H C~O)NHMe O
.q 4-CF3 H C(O)NMe2 O
,.~ 25 4-Cl H C(O)NMe2 O
~!~ 4-Br H C~O)NHEt O
, 4-CF3 H C(O)NHMe O
.. 4-CF3 H C(O)NHallyl O
4-cr3 ~ H C(O)N~Me)nllyl O
30 4-CF3 H C(O)NHPh-4-Cl O
.~ 4-OCF3 N C(S)NH2 o 4-CF3 H C(S)NHMe o 4-Cl H C(S)NMe2 O
4-Br H C(S)Me O
4-OCF3 H C~S)Et O
. 35 4-CF3 H C(S)NMe2 O
4-Cl H C(S)NHMe O

i .' ~ .
,, .

... . . .

~ '.'qL4 ~3 Rl R2 B X

4-Br 5-Cl H O
4-CF3 5-Cl Me O
4-OCF3 5-Cl Et 4-C1 5-Cl H O
4-SMe 5-Cl ~ o 4-CO2Et 5-Cl H O
4-Br 5-Cl CO2Me : 3-SMe 5-Cl CO2Me O
4-CO2Et 5-C1 2 4-CF3 5-Cl H 0 ' 4-OCF2H 5-Cl CO2Me O
4-C1 5-Cl CO2Me O
4-Br 5-Cl C(O)Me O
4-CF3 5-Cl C(O)Et O
. 4-OCF3 5-Cl C~O)NMe2 0 . 4-C1 5-F H 0 ~ 4-Br 5-F H . 0 ." 25 4-OCF2H 5-F H
4-C1 5-F C2Me O
4-Br 5-F C2Me O
4-CF3 5-F CO2Me O
4-OCF2H 5-F CO2Me 4-C1 5-F CO2Me O
4-Br 5-OCF2H C2Me O
4-C1 5-OCF2H C2Me O
4-8r 5-O~F2H C02Me O
4-CF3 5-OCF2~ C02Me O
5-OCF2H CO2Me O

4-OCF2H 5-OCF2H C02Me O
; 4-C1 5-Br CO2Me O

.
., '.

. . . . . . . - .:; . , . .. :, ,, . ~, . . . .

/ - ~
2~r'~ 4~

. _ 4-Br 5-No2 2 4-CF3 5-CF3CO2Me O
4-OCF3 5-OCH3 CO2Me O
4-CF3 5-OCH2Ph Me o 4-CF3 5-C~O)Me Et O
4-CF3 2 2 2 e O
4-CF3 5-I Me . 4-CF3 5-OCF3 Et O
: 4-CF3 5-Et C(O)Me O
4-CF3 5-Me C(O)CF3 o 4-CF3 5~CN Me O
4-cr3 5-OMe C2Me O
4-CF3 5-OMe CO2Et O
4-CF3 5-OMe H O
4-C1 5-OMe H O
. 4-CF3 5-CO2Me 6 13 , 4-CF3 5-SCF2H C(O)H o .~ 4-CF3 5-SO2Me (CH2)4Cl O
4-CF3 5,6-di-Cl H O
4-CF3 5,6-di-Cl C2Me o ,. 4-C1 4-F C2Me O
4-Br 4-F C2Me o .~ 4-CF3 4-Cl H O
4-OCF2H 4-Cl H O
4-OCF2H 4-Cl CO2Me O
4-CF3 4-Br H O
4-CF3 4-Br CO2Me 4-CF3 6-Cl CO2Me O

4-CF3 6-CF3 CO2Me O
4-CF3 4-Cl CO2Me .:

.

, Rl R2 B X

:: 4-CF3 4-F CO2Me O
4-CF3 6-Br 2 4-CF3 6-Me CO2Me O
4-CF3 4-Cl CO2Me O
4-CF3 4-F C02~e O
4-CF3 4-Br 2 : 4-Cl H H S
4-CF3 H Me S
, 15 4-C1 2 S
, 4-CF3 H H S
; 4-Cl H Me S
. 4-CF3 2 S
.` 4-C1 5-Cl H S
~ 4-C1 5-F Me S
'~ 20 4-CF3 5-F CO2Me S
4-CF3 B Ph 0 `; 4-OCF3 H Ph 0 4-Cl H Ph 0 .~ 4-Br H Ph 0 4-CF3 H ~-F-Ph O
~ 25 4-OCF3 H 4-F-Ph 0 .. q-Cl H 4-F-Ph 0 i 4-Br H 4-F-Ph 0 4-CF3 5-F Ph 0 .. 4-OCF3 5-F Ph 0 `1 4-C1 5-F Ph 0 3n 4-Br S-F Ph 0 4-CF3 5-F 4-Cl-Ph 0 4-OCF3 5-F 4-Cl-Ph ~ 0 .~ 4-C1 5-F 4-Cl-Ph 0 .` 4-Br 5-F 4-Cl-Ph O
! 4-CF3 5-F 4-F-Ph 0 4-OCF3 5-F 4-F-Ph 0 4-C1 5-F 4-F-Ph 0 .'~ . .; .

'' . .' .

4~

Rl R2 B X
4-8r 5-F 4-F-Ph 0 4-CF3 5-F Ph o 4-OCF3 5-Cl Ph 0 4-C1 5-Cl Ph 0 . 10 4-Br 5-Cl Ph O
4-CF3 5-C1 4-F-Ph 0 4-OCF3 5-C1 4-F-Ph 0 ~ 4-C1 5-C1 4-F-Ph 0 : 4-Br 5-C1 4-F-Ph O
4-CF3 5-C1 4-Cl-Ph 0 . 15 4-OCF3 5-C1 4-Cl-Ph 0 4-C1 5-C1 4-Cl-Ph 0 4-Br 5~C1 4-Cl-Ph O
4-CF3 5-8r 4-F-Ph 0 ' 4-OCF3 5-Br 4-F-Ph O
.~ 4-C1 5-Br 4-F-Ph 0 4-Br 5-Br 4-F-Ph 0 . 4-CF3 5-Br 4-Cl-Ph 0 4-OCF3 5-Br 4-Cl-Ph 0 4-C1 5-Br 4-Cl-Ph O
4-Br 5-Br 4-F-Ph 0 .. . . .
':
... .
` 30 .~ ' ' .
~ .

r --~ Zt ~,~d,~3 TABLE

l 2 . B X A
.~ ' .
4-CF2Cl H H O - O
;. 4-CF3 H B O O
4-Br H H 0 O
. 3-CF3 H H 0 0 4-Cl H H 0 0 3-Cl H H 0 O
"- 4-CF3 5-Br H 0 0 , 4-C1 5-Br H 0 0 :: 4-Br 5-Br H 0 0 '~ 15 4-C1 7-Br H 0 0 4-CF3 7-Br H 0 0 4-Br 7-Br H 0 0 4-CF3 H Me 0 0 4-OCF2H 5-F Me O O
4-Br H Me O O
4-OCF3 H CQ2Me O O
"f 4-CO2Me 5-Cl CO2Me O O
;; 4-Cl H C02CH2CF3 '`` 4-C1 5-Cl C(O)Me Q O
4-CF3 5-OCF2H Me O O
.1 4-CF3 5-F CQNHPh O O
,~, 4-C1 5-Cl n-Pr O O
~: 4-CF3 5-OCF2H CO2Me O O
'3 4-Cl H 4-Cl-Ph O O
., 9-CF3 5-C1 2 S O
4-CF2Cl H H O S
. 4-C1 5-F H O S

. 4-Cl H H O S
4-Br H H 0 ,S
3-~F3 H H 0 S
4-Cl H ~ 0 S

. : . -' . .' .
:........................................................................ '.,'.
:, ,.

. R2 B X A
3-CF3 5-Cl H O S
4-C1 5-Cl H O S
3-C1 5-Cl H O S
~: 4-Br 5-Cl H O S
4-C1 5-Cl H O S
.~ 4-CF3 6-Cl H O S
3-CF3 6-Cl H O S
': 4-C1 6-Cl H O S
4 3-C1 6-Cl H O S
: 15 4-Br 6-Cl H O S
4-C1 6-Cl H O S
4-CF3 5-Br H O S
3-CF3 5-9r H O S
, 4-C1 5-Br H O S
` 20 3-C1 5-Br H O S
4-Br 5-8r H O S
4-C1 5-Br H O S
. 4-CF3 4-Cl H O S
`~ 4-C1 4-Cl H O S
4-8r 4-Cl H O S
~i 4-CF3 N Me O S
4-OCF2H S-F Me O S
:,, 4-Br H Me O S
~' 4-OCF3 H C02Me O S
,~ 30 4-C02Me 5-Cl C02Me O S
., 4-Cl H C02CH2CF3 0 S
.. 4-CF3 5-OCF2H Me O S
, 4-CF3 S-F CONHPh O S
' 4-C1 5-Cl ~-Pr O S
4-CF3 5-OCF2H C02Me O S

~- 4-Cl H 4-Cl-Ph O S
'.

, .
: : -2 ~ - 9 _ _ 4-CF3 5-Cl CO2Me S S
4-CF2Cl H H . O NMe . 4-Cl S-F H O NMe 4-CF3 H Me O NMe 4-OCF2H 5_P Me ~Me : 4-Br ~ Me O NMe .~ 4-OCF3 H CO2Me 0 NMe 4-CO2Me 5-Cl CO2Me O NMe 4-Cl H CO2CH2CF3 0 NMe : 15 4-CF3 5-OCF2H Me O NMe 4-CF3 5-F CONHPh 0 NMe 4-C1 5-Cl n-Pr O NMe 4-Cl H 4-Cl-Ph O NMe :~ 4-CF3 5-Cl CO2Me S NMe 4-Cl H H S2 4-Br H H S2 , 3-CF3 H H S2 4-Cl H H S2 .' qe 3-Cl H H S2 4-CF3 5-Cl H O S2 3-CF3 5-Cl H O S2 4-Cl S-Cl H S2 3-C1 5-Cl H S2 .' 30 4-C1 5-C1 ~ S2 4-CF3 6-Cl H S2 : 3-CF3 6-CI H 0 S2 4-C1 6-Cl H S2 3-C1 6-Cl H S2 4-Br 6-Cl H O S2 4-C1 6-Cl H S2 4-C1 5-Cl Me SO2 ' .

A '3 : 136 Rl R2 B X A
- ---4-OCF3 H Et S2 4-Cl H CO2Me SO2 4-OCF3 5-Cl CO2Et 0 g2 3-CF3 H H 0 So() 4-CF3 H H O SO(a) 4-Br H H 0 So(~) 4-Cl H H O SO(a) 4-Cl H H O SO(~) 4-Cl H H 0 SO(a) : 15 4-Cl H H 0 SO(~) 3-Cl H H O SO(a) 3-Cl H H 0 SO(~) 4-CF3 5-Cl H 0 SO(a) 4-CF3 5-Cl H 0 SO(~) : 20 3-CF3 5-Cl H 0 SO() ~ 3-CF3 5-Cl H 0 SO(~) "~ 4-C1 5-Cl ~ . o SO(a) 4-C1 5-Cl H 0 SO(~) ' 3-C1 5-Cl H O SO(a) 3-C1 5-Cl H 0 SO(~) : 4-Br 5-Cl H 0 SO(a) ,.
; 4-Br 5-Cl H 0 SO(~) 4-C1 5-Cl H O SO(a) 4-C1 5-Cl H 0 SO(~) :., 4-CF3 6-Cl H 0 SO(a) ; 4-CF3 6-Cl H 0 50(~) 3-CF3 6-Cl H 0 SO(a) : 3-CF3 6-Cl H 0 gO(~) 4-C1 6-Cl H 0 ~O(a) 4-C1 6-Cl H 0 SO(~) 3-C1 6-Cl H 0 SO(a) 1. denotes ci6 rol~tionship to 8ub~tituent B;
~ d~note~ trans relation6hip to sub6titutent B.

: .: - ~ - : - . , :
.: . , . ~ , . : ~ . : -~` .
~ z ~ ~ 4~

3-Cl 6-Cl H 0 SO(~) 4-Br 6-Cl ~ 0 SO5) 4-Br 6-Cl H 0 SO(~) 4-Cl 6-Cl ~ o SO(a) 4-Cl 6-Cl H 0 æO(~) 3-CF3 H H 0 SO(~) 4-CF3 H H O SO(~) 4-CF3 5-Cl CO2Me N-allyl : 4-OCF3 5-Cl C02Me o N-CH2Ph : 15 4-CF3 H H O NH
; 4-CF3 H CO2Me 0 NH
,, 4-CF3 5-Cl H 0 NMe . 4-CF3 5-Cl C02Me O NMe 4-CF3 5-Cl CO2Me 0 NC(O)CH3 . ., ^i 20 4-CF3 S-Cl CO2Me 0 NCO2CH3 ;,, 4-CF3 5-Cl CO2Me o NSO2CH3 ., 4-CF3 5-Cl CO2Me NCB2Ph : , 4-CF3 5-Cl CO2Me 0 N-allyl . 4-CF3 5-C1 CO2Me 0 NCO2C(CH3)3 :; 25 4-CF3 H Ph 0 S . :':
;~ 4-OCF3 H Ph 0 S
s 4-Cl H Ph 0 S
S, 4-Br H Ph 0 S
~, 4-CF3 H 4-F-Ph 0 S :.
3~ 4-OCF3 H 4-F-Ph 0 S
' 4-CI H 4-F-Ph 0 S
4-S3r H 4-F-Ph 0 S .
: 4-CF3 5-F Ph O S ;
, 4-OCF3 5-F Ph 0 S `
. 35 4-Cl 5-F Ph O S ~:~
: 4-Br 5-F Ph O S
. 4-CF3 5-F 4-Cl-Ph 0 S
':.

., .
., ., ~i .

.. ,., . . , .,. , . , . . . ~ , . . . .

~ - "
~ t ~; ~ $ A~

4-C1 5-F 4-Cl-Ph 0 S
4-Br 5-F 4-Cl-Ph 0 S
4-CF3 5-F 4-F-Ph 0 S
4-OCF3 5-F 4-F-Ph O S
4-C1 5-F 4-F-P~ 0 S
4-Br 5-F 4-F-Ph 0 S
4-CF3 5-Cl Ph 0 S
4-OCF3 5-Cl Ph 0 S
4-C1 5-Cl Ph 0 S
4-Br 5-Cl Ph 0 S
4-CF3 5-C1 4-F-Ph 0 S
: 4-OCF3 5-C1 4-F-Ph 0 S
4-C1 5-C1 4-F-Ph 0 S
4-Br 5-C1 4-F-Ph 0 S
4-CF3 S-Cl 4-Cl-Ph 0 S
4-OCF3 5-C1 4-Cl-Ph O S
. 4-C1 5-C1 4-Cl-Ph 0 S
~ 4-CF3 5-Br 4-F-PH 0 S
: 4-OCF3 5-Br 4-F-Ph 0 S
`: 25 4-C1 5-Br 4-F-Ph 0 S
4-Br 5-Br 4-F-Ph 0 S
4-OCF3 5-Br 4-Cl-Ph 0 S
4-C1 5-Br 4-Cl-Ph 0 S
4-Br 5-Br 4-Cl-Ph 0 S
4-CF3 S-Br 4-Cl-Ph 0 S
4-CF3 H Ph O O
4-OCF3 H Ph O O
4-Cl H Ph 0 O
4-Br H Ph O O
. 35 4-CF3 H 4-F-Ph O O
4-OCF3 H 4-F-Ph 0 O
4-Cl H 4-F-Ph 0 O
. .
.
..

., 4-Br H ~ 4-F-Ph 0 O
4-CF3 5-F Ph 0 O
4-OCF3 5-F Ph O O
4-C1 5-F Ph O O
4-Br 5-F Ph O O
4-CF3 5-F 4-Cl-Ph O O
. ., 4-OCF3 5-F 4-Cl-Ph 0 O
~- 4-C1 5-F 4-Cl-Ph 0 O
4-Br 5-F 4-Cl-Ph O O
lS 4-CF3 5-F 4-F-Ph O O
4-OCF3 5-F 4-F-Ph O O
4-C1 5-F 4-F-Ph O O
4-8r 5-F 4-F-Ph O O
4-CF3 5-Cl Ph 0 o 4-OCF3 5-Cl Ph o O
4-C1 5-Cl Ph O O
4-Br 5-Cl Ph O O
. 4-CF3 5-C1 4-F-Ph O O
., 4-OCF3 5-C1 4-F-Ph O O
:, 25 4-C1 5-C1 4-F-Ph O O
4-Br 5-Cl 4-F-Ph O O
. 4-CF3 5-C1 4-Cl-Ph O O
4-OCF3 5-C1 4-Cl-Ph 0 O
4-C1 5-C1 4-Cl-Ph O O
4-Br 5-F 4-F-Ph O O
4-CF3 S-Br 4-F-,PH O O
4-OCF3 5-Br 4-F-Ph O O
4-C1 5-Br 4-F-Ph O O
4-Br 5-Br 4-F-Ph O O
4-CF3 5-Br 4-F-Ph O O
4-OCF3 5-Br 4-Cl-Ph O O

4-C1 5-Br 4-Cl-Ph O O

: '~
,'.
}, .. , ::- :; : . ., ., .,. . : , :; ~ .. .... ~ . .

~? '~ L~i 3 Rl Rz B X A
: 4-Br 5-Br 4-Cl-Ph 0 O
4-CF3 5-Br 4-Cl-Ph 0 O
4-CF3 5-F 4-Cl-Ph SO
4-C1 5-F 4-Cl-Ph 0 SO
4-Br 5-F 4-Cl-Ph 0 SO
4-CF3 5-C1 4-Cl-Ph SO
4-OCF3 5-Cl g-Cl-Ph SO
4-C1 5-C1 4-Cl-Ph 0 SO
4-Br 5-C1 4-Cl-Ph 0 SO
, 15 4-CF3 H 4-Cl-Ph SO
: 4-OCF3 H 4-Cl-Ph 0 SO
4-Cl H 4-Cl-Ph O SO
4-Br H 4-Cl-Ph O SO
4-CF3 5-F 4-Cl-Ph O SO
4-OCF3 5-F 4-Cl-Ph 0 SO
4-C1 5-F 4-Cl-Ph 0 SO
4-Br 5-F 4-Cl-Ph 0 SO
4-CF3 5-C1 4-Cl-Ph 0 SO
4-OCF3 5-C1 4-Cl-Ph 0 SO
: 25 4-C1 5-C1 4-Cl-Ph 0 SO
4-Br 5-C1 4-Cl-Ph 0 SO
4-CF3 H 4-Cl-Ph 0 SO
` 4-OCF3 H 4-Cl-Ph 0 SO
4-Cl H '- 4-Cl-Ph 0 SO
4-Br H 4-Cl-Ph 0 SO
.~ 4-CF3 5-F 4-Cl-Ph 0 NMe ~-OCF3 5-F 4-Cl-Ph O NMe 4-C1 5-F 4-Cl-Ph 0 NMe 4-Br 5-F 4-Cl-Ph 0 NMe 4-CF3 5-C1 4-Cl-Ph 0 NMe . 4-OCF3 5-C1 4-Cl-Ph 0 NMe 4-C1 5-C1 4-Cl-Ph 0 NMe .' ~, .
.
'.',~'.
: ' ' : :' :,: ' : : ' '' ' ' : . :' . ~ - ~ . :: ' . ,:- '. ,' . ,: ' F~t ~

~ .
.-. ' .
R2 B X A :
.
4-Br 5-C1 4-Cl-Ph 0 NMe .
4-CF3 H 4-Cl-Ph O NMe 4-OCF3 H 4,-Cl-Ph O NMe 4-Cl H 4-Cl-Ph O NMe 4-Br H 4-Cl-Ph 0 NMe 4-CF3 5-C1 4-Cl-Ph 0 O
. 4-OCF3 5-Cl q-Cl-Ph 0 O
4-C1 5-C1 4-Cl-Ph 0 O
' 4-Br 5-C1 4-Cl-Ph O O :.
4-OCF2CF2H H Ph 0 O -.

4-CF3 ~ CO2CH3 0 4-Br 5-F R O O
` 4-OCF3 5-F R 0 O . ;
l ~-CF3 5-Cl H 0 O ;' ,~ 4-Br 5-Cl H 0 O
.:~ 25 4-OCF3 5-Cl H 0 O
4-CF3 5-F Me 0 O
. 4-Br 5-F Me 0 O
' 4-OCF3 5-F Me 0 O
.~ 4-CF3 H CO2Me O O
4-OCF3 H CO2Me 0 O
~ 4-Cl H CO2Me 0 O
.' 4-Hr H CO2Me 0 O

~-CF3 5-F CO2Me 0 O
4-OCF3 5-F CO2Me 0 O
4-C1 5-F CO2Me 0 O
4-Br 5-F CO2Me 0 O
4-CF3 5-Cl CO2Me 0 O
4-OCF3 5-CI CO2Me 0 O ~;

~ ~ .

- ~ : . . .. .
. .

Z ~ a ~ :

~1 R2 B X A
4-C1 5-Cl CO2Me 0 O
4-Br 5-Cl CO2Me O O
4-CF3 5-Br C2Me0 O
4-OCF3 5-Br C2MeO O
4-C1 5-Br CO2Me 0 O
4-Br 5-Br CO2Me 0 O
4-CF3 5-F COzMe 0 S
4-OCF3 5-F CO2Me 0 S
4-Cl S-F CO2Me 0 S
: 15 4-Br 5-F CO2Me 0 S
4-CF3 5-Cl CO2Me S
.. 4-OCF3 5-Cl CO2Me 0 S
4-C1 5-Cl CO2Me 0 S :
. 4-Br 5-Cl CO2Me 0 S
.. 20 4-CF3 5-F C02Me o N CH3 ~: 4-OCF3 5-F CO2Me N-CH3 4-C1 5-F CO2Me N-CH3 4-Br 5-F CO2Me N-CH3 . 4-CF3 5-Cl CO2Me 0 N-CH3 25 4-OCF3 5-Cl C2Me 0 N-CH3 .. 4-C1 5-Cl CO2Me 0 N-CH3 4-Br 5-Cl CO2Me O N-CB3 :, .

~ .

: . ,:
~ 35 ~:

. : :

. . ~ .
!;

., . ,. . ,, . ~ . . .. . ~ - . , -.. . , . , : .. : ,.. . . .: . , .. :. . . . :: .
, . . . . . . . . . . . .. . .

: 143 .~ ' TABL~
!

: 5 ; Rl 2 p y :.
4-OCF3 H H Me CH2 4-CF3 . H H C(O)Me C~2 4-F H C2Me Me CH2 : 4-OCF2H H CO2Me C(O)Me CH2 . 4-CF3 H Me C(O)CF3 CH2 4-Cl H Me C02Et C ..
4-CF3 H CO2C~2CF3 Me .: 4-OCF2H H C02Et Me CH2 . 15 4-OCF3 H CO2CH2CH2Cl Me CH
4-Br H CONHMe Me CH2 .. 4-CF3 H CO2Me C(O)Me CH2 .~ 4-CF3 H CO2Me Me C~2 4-CF3 H CO2Me CO2Me CH2 4-CF3 5-Cl CO2Me C(O)Me CH2 .~ 4-CF3 5-Cl CO2Me Me CH2 4-CF3 5-Cl CO2Me CO2Me CH2 ;~î 4-CF3 4-F CO2Me C(O)Me CH2 ..
.~, 4-CF3 5-F CO2Me C(O)Me CH
.~ 25 4-CF3 4-F C2Me C2Me CH2 ~ 4-CF3 5-F CO2Me CO2Me CH
.~ 4-CF3 H H CO2-t-Ru CH2 ,`! 4-CF3 S-Cl CO2Me SN(iPr)P(O)(OCH3)(CH3) CH2 .~, 4-CF3 5-Cl CO2Me SP(O)(Oc2H5)2 CH2 ~
.`, 4-CF3 5-Cl CO2Me SN(iPr)2 CH2 ., 4-CF3 H C02Me SN(iPr)P(O)(OC2H5)tPh) 2 ..

.~ 4-CF3 H CO2Me SP(O)(OiPr)2 CH2 4-CF3 H CO2Me SN(cec Bu)2 CH2 ~;

~ , ' .' :1 ' .~ ~ .
, . , . , . . , . - .. .

~.: ' ' :' ,; . :'.:' ,' ' .: ': '. ' . ~ . .

Rl R2 8 Y A

O
4-CF3 H C2Me SNP~OEt)2 CH2 O ., .
9-Cl H C02Me SNP(OEt)2 CH2 O
4-OCF2H H C2Me SNp(oEt)2 2 4-CF3 5-Cl C02Me SN(iPr)COC2H5 2 4-CF3 4-F C02Me SN(iPr)O'OC2H5 4-CF3 5-F C02Me SN(iPr)COC2H5 CH2 ' O
4-CF3 5-C1 4-Cl Phenyl SN(iPr)COC2H5 CH2 .: O
4-CF3 4-F C02Me SN(iPr)COC2H5 CH2 4-CF3 5-F C02Me "
. O
~ 4-CF3 H C2Me SN(iPr)COC2H5 CH2 .,` O
;~ .. ;
; 4-CF3 H C02Me SN(CH3)CO(c~2)3cH3 CH2 ., O
f 25 4-Cl H C02Me SN(cH3)co(cH2)3cH3 CH2 . O :
~ 4-CF3 5-Cl C02Me SN(CH3)00(cH2)3cH3 :. 4-CF3 4-F C02Me SN(CH3)CO(cH2)3cH3 CH2 ,., O
~, 30 4-CF3 5-F C02Me SN~CH3)co(cH2)3cH3 CH2 . O :
. 4-CF3 5-C1 4-Cl-Phenyl SN~CH3)CO~CH2)3CH3 C 2 ,. .. . .
4-CF3 4-F C02Me SN~CN3)CO~cH2)3c~3 CH2 O
4 CF 5-F C02Me SN~CH3)00~cH2)3cH3 C~2 ~!' 4-CF3 H C02Me SN~cH3)co~c~2)3cH3 CH2 ., - .
. ' "'. .
::
, - 2?~r.,~L4~

:~

.4-CF3 H C2Me SN(iPr)SO2CH3CH2 4-C1 H CO M SN(iPr)S02CH3CH2 :~
4-OCF2H H C02Me S!~ ( iPr ) S02CH3 CH2 4 -F H C02Me SN t iPr ) S02CH3 C~2 4-CF3 5-Cl C02Me SNtiPr)S02CH3CH2 4-CF3 4-F C02Me SN(iPr)S02CH3CHz .. 4-CF3 5-F C02Me SN(iPr)S02CH3CH2 4-CF3 5-CI ~-Cl-Ph~nyl SN(iPr)S02CH3 C~2 l 4-CF3 4-F CO2Me SN(1Pr)SO2CH3CH2 15 4-CF3 5-F CO2Me SN(iPr)SO2CH3CH2 4-CF3 H C02Me SN ( iPr ) S02CH3 CH2 4-CF3 5-C1 CO2Me SN(CH3)SO2PhCH2 .~ 4-CF3 4-F CO2Me SN(CH3)SO2PhCH2 . . 4 -CF3 5-F C02Me SN ( CH3 ) 502Ph CH2 S 4-CF3 5-C1 4-Cl-Phenyl SN(CH3)S02Ph CH2 . 2 4-CF3 4-F C02Me SN ( CH3)SO2Ph CH2 4-CF3 5-F C02Me SN( CH3)SO2PhC~2 ,`6 4-CF3 H C02Me SN( CH3)SO2PhCH2 i~
l o .:~' 2 5 4-CF3 H' CO2Me SCOCH2CH2CH2C~3 CH2 -, 4-C1 H C02Me ScocH2cH2c~2cH3 CH2 " 4-OCF2H H CO2Me SCOC82CH2CH2CH3 Q2 :~
l o ~ j-OCF2 H C02Me SCOCH2CH2CH2CH3 CH2 ~ o :- 4-F H C02Me SCOCH2CH2cH2cH3 CH2 o !
.; 4-CF3 5-Cl C02Me SCOCH2CH2CH2cH3 . CH2 .~ O
4-CF3 4-F CO2Me SCOCH2C~2CH2CH3 CH2 4-CF3 5-F CO2Me SCOCH2CH2CH2CH3 CH2 .

'I

.

~ .

2 ,~? ~3 ~ ~.~ 4 9 :

'', .
Rl R2 B Y A
-O
4-CF3 " CH2 O
4-CF3 4-F CO2Me SCOCH2CH2CH2CH3 CH2 o 4-CF3 5-F CO2Me SoocB2cH2c~2cH3 C~2 4-CF3 H C2Me SCOCH CH CH2CH3 CH2 4-CF3 5-C1 CO2Me M 2 2 CH2 4-OCF3 5-C1 CO2Me Me CH2 4-Br 5-Cl CO2Me Me CH2 4-CF3 5-F CO2Me COCH3 CH2 ~. 4-OCF3 5-F CO2Me COCH3 CH2 4-Br 5-F CO2Me COCH3 CH2 4-CF3 5-Cl C02Me CO2CH3 C~2 4-OCF3 5-Cl CO2Me CO2CH3 CH2 2 0 4-Br 5-Cl CO2Me CO2CH3 CH2 . 4-CF3 5-F CO2Me COCF3 CH2 ~: 4-OCF3 5-F CO2Me COCF3 CH2 4-Br 5-F CO2Me COCF3 CH2 i; 2 5 4-CF3 4-C1 4-Cl-Ph Me CH2 - 4-OCF3 4-C1 4-Cl-Ph Me CH2 4-~3r 4-C1 4-Cl-Ph Me CH2 4-CF3 4-C1 4-Cl-Ph COCH3 CH2 4-OCF3 4-CL 4-Cl-Ph COCH3 CH2 ,- 4-Br 4-C1 4-Cl-Ph COC~3 CH2 4-CF3 4-C1 4-Cl-Ph C2CH3 CH2 4-OCF3 4-C1 4-Cl-Ph CO2CH3 CH2 4-Br 4-C1 4-Cl-Ph CO2CH3 CH2 4-CF3 4-C1 4-Cl-Ph COCF3 CH2 , 4-OCF3 4-C1 4-Cl-Ph COCF3 CB2 , 35 4-Br 4-C1 4-Cl-Ph COCF3 CH2 ~. .' ' .

.
,, .
.
. .

~ Z~-~f,~. . 4-~

Rl R2 B y 4-CF3 4-C1 4-Cl-Ph CO2CH2CH3 CH2 4-OCF3 4-C1 4-Cl-Ph CO2CH2CH3 CH2 4-Br 4-C1 4-Cl-Ph C02CH2CH3 CH2 4-CF3 4-C1 4-Cl-Ph Me CH2 4-OCF3 4-C1 4-F-Ph ~e CH2 4-Br 4-C1 4-F-Ph Ne CH2 Ç-CF3 4-C1 4-F-Ph COCE13 CH2 4-OCF3 4-C1 4-F-Ph COCH3 CH2 4-Br 4-C1 4-F-Ph COCH3 2 4-CF3 4-C1 4-F-Ph CO2CH3 CH2 4-OCF3 4-C1 4-F-Ph C2CH3 CH2 4-Br 4-C1 4-F-Ph CO2CN3 CH2 4-CF3 4-C1 4-F-Ph COCH2CH3 CH2 4-OCF3 4-C1 4-F-Ph COCH2CH3 CH2 4-Br 4-C1 4-F-Ph COCH2CH3 CH2 2 4-CF3 H Me Me NMe 4-CF3 S-Cl C2Me Me S
4-CF3 5-Cl Me tSe NMe 4-CF3 5-Cl Me C(O)Me S
4-CF3 5-F CO2Me C(O)Me NMe 4-CF3 5-F Me C(O~Me SO
~, 4-CF3 H CO2Me SCC13 4-CF3 N CO2Me SCC13 NMe . 4-CF3 H Me CO2Me . 4-CF3 5-OCF2H CO2Me n-Pr NMe 4-CF3 5-CF3 Me C(O)CF3 O
4-CF3 5-CF3 Me C(O)CF3 NMe : 4-CF3 5-Cl CO2Me SMe O
4-CF3 H H Me S
4-CF3 H H CO2Me S

. 35 4-CF3 H H C(O)Me S
4-CF3 5-Cl H C(O)Me S

. ,:
': , ;'~ .
, ,i :
.

- . . : - . ~: , .. .

.

~o~a~9 2 ~ Y A
4-CF3 5-Cl H CO2Me S
4-CF3 5-Cl H Me S
4-Cl H H C(O)Me S
- 4-Cl H H Me S
4-C1 5-Cl H C(O)Me . S
4-C1 5-Cl H Me S

4-CF3 5-Cl CO2Me SN(iPr)COC2H5 4-CF3 4-F C2Me SN(iPr)COC2H5 :~
.. 4-CF3 5-F CO2Me SN(iPr)COC2H5 O :~
O ,:
4-CF3 5-Cl 4-Cl-Phenyl SN(;Pr)COC2H5 O
4-CF3 4-~ 4-Cl-Phenyl SN(iPr)COC2H5 !`
` 20 4-CF3 5-F 4-Cl-Phenyl SN(iPr)COC2H5 ., o ,.
. 4-CF3 H 4-Cl-Phenyl SN(iPr)COC2H5 .~ O
;, ..
~ 4-CF3 H CO2Me SN(CH3)CO(CH2)3CH3 O
`, 25 :
' 4-Cl H CO2Me SN(cH3)co(cH2)3cH3 .. 4-CF3 5-Cl CO2Me SN(cH3)co(cH2)3cH3 ~, . . .
4-CF3 4-F CO2Me SN(CH3)cO~cH2)3cH3 O
. "
4-CF3 5-F CO2Me SN(CH3)cO(cH2)3cH3 O
2, . :
. , .

- .- .

~ ; r ' ' ' ~ ' , ' ' ' ' ' ~ ' ' ' " ~ ' ' ' ' ' ' ' ' 2~001 49 1 2 ~ y A
_ O
4-CF3 5-Cl 4-Cl-Phenyl SN(CH3)cO(cH2)3c~3 ,, 4-CF3 4-F 4-Cl-Phenyl SN(CH3)CO(CH2)3CH3 O

4-CF3 5-F 4-Cl-Phenyl SN(cH3)co(cH2)3cH3 o O
4-CF3 H 4-Cl-Phenyl SN(CH3)CO(CH2)3CH3 O
4-CF3 H CO2Me SN(iPr)SO2CH3 4-Cl H C2Me SN(iPr)SO2CH3 4-OCF3 H CO2Me SN(iPr)SO2CH3 . 4-CF3 5-Cl CO2Me SN(iPr)SO2CH3 O
.~ 4-CF3 4-F CO2Me SN(iPr)SO2CH3 O
.` 4-CF3 5-F CO2Me SN(iPr)SO2CH3 O
~`' 20 4-CF~ 5-C1 4-Cl-Phenyl SN(iPr)SO2CH3 4-CF3 4-F 4-Cl-Phenyl SN(iPr)SOzCH3 O
. 4-CF3 5-F 4-Cl-Pbenyl SN(iPr)SO2CH3 4-CF3 H 4-Cl-Phenyl SN(iPr)SO2CH3 O
4-CF3 H CO2Me SN(CH3)SO2ph o 4-Cl H CO2Me S~(CH3)SO2Ph O
.~4-OCF2H H CO2Me SN(CH3)SO2Ph O
-OCF3 H CO2Me SN(CH3)SO2Ph O
- 4-F ~ C02Me SN(cH3)so2ph O
-CF3 5-Cl CO2Me SN(cH3)so2ph O
4-CF3 4-F CO2Me SN(cH3)so2ph O
4-CF3 5-F CO2Me SN(CH3)SO2Ph O
4-CF3 5-C1 4-Cl-Phenyl SN(CH3)SO2Ph O
4-CF3 4-F 4-Cl-Phenyl ~N(CH3)sO2ph O
4-CF3 5-F 4-Cl-Phenyl SN(CH3)SO2Ph O
3 4-CF3 H 4-Cl-Phenyl SN(cH3)so2ph O

~ , .

., .. ~.

-:. , . , . .. ,, , ,,. . , , ~ ., , , . . , , . , . :, . . . . . . . . .

- 2~ 4~3 ,:

:
Rl R2 8 Y A

~ O
: 4-CF3 H C2Me SCOCH2C~2c~2cH3 O
: O
4-CF3 5-Cl CO2Me ScocH2c~2cH2cH3 . 10 ,, 4-CF3 4-F CO2Me sCOCH2CH2CH2CH3 o 4-CF3 5-F C02Me SCOCH2CH2cH2cH3 . 4-CF3 5-C1 4-Cl-Phenyl SCOCH2CH2CH2CH3 O
: 15 . 4-CF3 4-F 4-Cl-Phenyl SCOCH2CH2CH2CH3 o . :~ ,, ~ ~
~ 4-CF3 5-F 4-Cl-Phenyl SCOCH2CH2CH2cH3 ~
~; ::
i" 20 4-CF3 H 4-C1-Phenyl SCOCH2CH2CH2CH3 :! 4-CF3 5-Cl CO2Me SN(ipr)p(ocH3)cH3 S

: O
. 4-CF3 5-Cl CO2Me -SP(OC2H5)2 S
4-CF3 5-Cl C2Me -S-N(iPr)2 S
:~ 25 O . ~:
~, 4-CF3 H CO2Me SN(ipr)p(oc2H5)ph S
~ ! O
.~, 4-CF3 H CO2Me -SP(OiPr)2 S
4-CF3 H C2~e _s-N(s-Bu)2 S :.
l1 C-CF3 i3 C2Me ~d (Ol~t)3 S

.. , 4-Cl H CO2Me SNP(OEt)2 S
:~ .. ....
~, 35 4-OCF2H H CO2Me SNp(oEt)2 S

`) ~.,' :. .
., ~ .

: . ,., , ,. ".,. - ,; ,., ,';'' ';.'. ' ' ' '' . ' ..' '.' ': '. ' ' '' ' ~',' ' ".:,-' ".:

Rl R2 B Y A

O
: 4-CF3 H CO2Me SN(iPr)COC2H5 O
O

4-Cl ~ C02~e SN(iPr)COC2~5 :: 4-OCF2H H CO2Me SN~iPr)COC2H5 O
,~ O
4-OCF3 N CO2Me O
. .. . .
4-F H CO2Me SN(iPr)COC2H5 O
~ O
4-CF3 5-Cl CO2Me SN(iPr)COC2H5 O
,~ O
~. 20 4-CF3 4-F CO2Ne SN(iPr)COC2H5 O
.~ 4-CF3 5-F CO2Me SN(iPr)COC2H5 O ::
':` "
4-CF3 5-C1 4-Cl-PheDyl SN(iPr)COC2H5 - '~ .
4-CF3 4-F 4-Cl-Phenyl SN(iPr)COC2H5 O

4-CF3 5-F 4-Cl-Phenyl SN(iPr)COC2H5 O
O
;. 4-CF3 H 4-Cl-Phenyl SN(iPr)COC2H5 . O
4-CF3 H CO2Me SN(CH3)co(cH2~3CH3 .. .
4-Cl H CO2Me SN(CH3)CO(cH2).3c 3 S
: 35 ;~ 4-OCF2H H CO2Me SN(CH3)CO(cH2)3c~3 S
O -:
4-OCF3 H CO2Me SN(cH3)co(cH2)3cH3 , ' .
' .

~, 2~ 43 , : 152 !`
Rl 2 F Y A
5 . -~
O
. 4-F H C02Me SN(cH3)co(cH2)3cH3 S
o 4-CF3 5-Cl C2Me ~N(CN3)C05CH2~3CH3 S .
' ., ', : 4-CF3 4-F CO2Me SN(cH3)co(cH2)3cH3 S
O
4-CF3 5-F C2Me SN(CH3~CO(c~2)3c 3 , 15 4-CF3 5-C1 4-Cl-Phenyl SN(CH3)CO(cH2)3cH3 S
,:: O
"
. 4-CF3 4-F 4-Cl-Phenyl SN(CH3)CO(cH2)3cH3 S
" : .
4-CF3 5-F 4-Cl-Phenyl SN(CH3)CO(cH2)3cH3 S
4-CF3 5-Cl CO2Me SN(iPr)SO2CH3 S . .
4-CF3 4-F CO2Me SN(iPr)SO2CH3 S --;
4-CF3 5-F CO2Me SN(iPr)SO2CH3 S ~ ~, 4-CF3 5-C1 4-Cl-Phenyl sN(ipr)so2c~3 S ~ , 4-CF3 4-F 4-Cl-Phenyl SN(iPr)SO2CH3 S ~.
4-CF3 5-F 4-Cl-Phenyl SN(iPr)SO2CH3 S .r ~;. 4-CF3 H 4-Cl-Phenyl SN(iPr)SO2CH3 S ~ :
:J :.
,, " !~, , -~' 30 4-Cl H CO2Me SN(cH3)co(cH2)3cH3 NCX3.

4-OCF2H H CO2Me SN(CH3)CO(CH2)3CH3 ~CH3 ~ !
4-OCF3 H C02Me SN(CH3)CO(CH2)3CH3 NCH3 O
4-F H CO2Me SN(CH3)CO(CHz)3CH3 ,~ '.',"
, : ,' .

.~
-"` 2~r,'~ 3 :~ 153 Rl R2 B Y A

4-CF3 5-Cl C2Me SN(C~3)cO(c~2)3cH3 NC~3 .
4-CF3 4-F CO2Me SN(cH3)co(cH2)3cH3 ~CH3 . 4-CF3 5-F CO2Me SNtcH3)co(cH2)3cH3 NCH3 : 4-CF3 ~-Cl 4-Cl-Phenyl SN(CH3)cO(cH2)3cH3 NCH3 : O
:~ 15 "
4-CF3 4-F 4-Cl-Phenyl SN(CH3)cO(cH2)3Q3 NCH3 ~ -"
. 4-CF3 5-F 4-Cl-Phenyl SN(cH3)co(cH2)3cH3 NCH3 .~, O

4-CF3 H 4-Cl-Phenyl SN(CH3)cO(cH2)3cH3 NCH3 4-CF3 H CO2Me SN~iPr)SO2CH3 NCH3 4-Cl H CO2Me SN~iPr~SO2CH3 NCH
4-OCF2H H CO2Me SN~iPr)SO2CH3 NCH3 . 4-OCF3 H C02Me SN~iPr)S02CH3 NCH3 :. 25 4-F H CO2Me SN(iPr)SO2CH3 NC~3 . 4-CF3 5-Cl CO2Me SN~iPr)SO2CH3 NCH3 4-CF3 4-F CO2Me SN(iPr)SO2CH3 NCH3 4-CF3 5-F CO2~e SN~iPr)SO2CH3 NCH3 4-CF3 5-C1 4-Cl-Phenyl SN~iPr)SO2CH3 NCH3 4-CF3 4-F 4-CI-Phenyl SN~iPr)SO2CH3 NCH3.
. 4-CF3 5-F 4-Cl-Phe~yl SN~lPr)SO2CH3 NCH3 4-CF3 ~ 4-Cl-Phenyl .SN~iPr)SO2CH3 NCH
4-CF3 ~ CO2Me SN~s-Bu)5O2cH2c~2cH3 ~CH3 4-Cl H CO2Me SN~C-~u)so2cH2cH2cH3 NC~3 2 H CO2Me 6N~s-Bu)SO2CH2C~2cH3 NCH3 4-OCF3 H CO2Me SN~-Bu)SO2CH2CH2CH3 NCN3 4-F H CO2Me SN(b-Bu)so2cH2cH2cH3 NCH3 ~ : .
.. . .
:

-~` Z~ 4~) : 5 . --:. 4-CF3 5-Cl CO2Me SN(s-Bu)So2CH2CH2CH3 NCH3 4-CF3 4-F CO2~e SN(6-Bu)SO2CH2CH2C~3 NCH3 4-CF3 S-F CO2Me SN(6-Bu)SO2CH2CH2CH3 NCH3 4-CF3 S-C~ 4-CI-Phenyl SN(~-Bu)SO2CH2CH2C~3 NCH3 4-CF3 ~-F 4-Cl-Phen~l SN(~-Bu)SO2CH2CH2CH3 NCH3 4-CF3 5-F 4-Cl-Phenyl SN(6-au~SO2CH2CH2CH3 NCH3 4-CF3 H 4-Cl-Phenyl SN(~-Bu)5O2cH2cH2cH3 NC~3 4-CF3 S-Cl CO2Me Me S
. 4-OCF3 5-Cl CO2Me Me S
: 15 4-Br 5-Cl CO2Me Me S
4-CF3 S-F CO2Me COCH3 S ~ ~. .
4-OCF3 5-F CO2Me COCH3 S ~, ~'~
4-8r 5-F CO2Me COCH3 S .:
4-CF3 5-Cl CO2Me CO2CH3 S
4-OCF3 5-Cl CO2Me CO2CH3 S ~ :
4-Br 5-Cl CO2Me CO2CH3 S
4-CF3 5-F CO2Me COCF3 S :
4-OCF3 5-F CO2Me COCF3 S :
. 4-Br S-F CO2Me COCF3 S
" 25 4-CF3 4-C1 4-Cl-Ph Me S
, 4-OCF3 4-C1 4-Cl-Ph Me S
:~ 4-Br 4-C1 4-Cl-Ph Me S
4-CF3 4-C1 4-Cl-Ph COCH3 S
, 4-OCF3 4-C1 4-Cl-Ph COCH3 S
4-Br 4-C1 4-Cl-Ph COCH3 S
4-CF3 4-C1 4-Cl-Ph CO2CH3 S .:
4-OCF3 4-C1 4-Cl-Ph CO2CH3 S :
4-Br ~-Cl 4-Cl-Ph CO2CH3 S
, 4-CF3 4-C1 4-Cl-Ph COCF3 S ~ i .
4-OCF3 4-C1 4-Cl-Ph COCF3 S
4-Br 4-C1 4-Cl-Ph COCF3 S

' .-- .
.1 .. .

.

2~$~

lS5 Rl R2 B Y A

4-CF3 4-C1 4-Cl-Ph CO2CH2CH3 S
4-OCF3 4-C1 4-Cl-Ph CO2CH2CH3 S
4-Br 4-C1 4-Cl-Ph CO2CH2CH3 S
4-CF3 4-C1 4-F-Ph Me S
4-OCF3 4-C1 4-F-Ph Me S
`~ 4-Br 4-C1 4-F-Ph Me S
4-CF3 4-C1 4-F-Ph COCH3 S
4-OCF3 4-C1 4-F-Ph COCH3 S
4-Br 4-C1 4-F-Ph COCH3 S
4-CF3 4-C1 4-F-Ph CO2CH3 S
4-OCF3 4-C1 4-F-Ph CO2CH3 S
4-Br 4-C1 4-F-Ph CO2CH3 S
4-CF3 4-C1 4-F-Ph COCH2CH3 S
4-OCF3 4-C1 4-F-Ph COCH2CH3 S
~: 20 4-Br 4-C1 4-F-Ph COCH2CH3 S
. 4-CF3 5-Cl CO2Me Me O
4-OCF3 S-Cl CO2Me Me O
4-Br 5-Cl CO2Me Me O
' 4-CF3 5-F CO2Me COCH3 O
4-OCF3 5-F CO2Me COCH3 ;~ 4-Br 5-F CO2Me COCH3 ~ 4-CF3 5-Cl CO2Me CO2CH3 .. 4-OCF3 5-Cl CO2Me CO2CH3 :....................... 4-Br 5-Cl CO2Me CO2CH3 o 4-CF3 5-F C02~e COCF3 4-OCF3 5-F CO2Me COCF3 O
r 5-F C02Me COCF3 4-CF3 4-C1 4-Cl-Ph Me O
4-OCF3 4-C1 4-Cl-Ph ~e O
4-Br 4-C1 4-Cl-Ph Me O

4-CF3 4-C1 4-Cl-Ph COCH3 .
.

:~:. . . . .: . : . :

2 ~ ~ ~3 ~ ~ ~ 3 Rl R2 B Y A
.__ _ __ 4-OCF3 4-C14-Cl-Ph COCH3 .
4-Br 4-C14-Cl-Ph COCH3 3 4-CF3 4-C14-Cl-Ph CO2CH3 O ~ s 4-OCF3 4-C14-Cl-Ph CO2CH3 O
: 10 4-Br 4-C14-Cl-Ph CO2CH3 O
4-CF3 4-C14-Cl-Ph COCF3 O
: 4-OCF3 4-C14-Cl-Ph COCF3 .~ 4-Br 4-C14-Cl-Ph COCF3 O
4-CF3 4-C14-Cl-Ph CO2CH2CH3 O '-4-OCF3 4-C14-Cl-Ph CO2CH2CH3 4-Br 4-C14-Cl-Ph CO2CH2CH3 O .
4-CF3 4-C14-F-Ph Me O
4-OCF3 4-C14-F-Ph Me O
~ 4-Br 4-C14-F-Ph Me O :
: 20 4-CF3 4-C14-F-Ph COCH3 4-OCF3 4-C14-F-Ph COCH3 O
4-13r 4-C14-F-Ph COCH3 A~ 4-CF3 4-C14-F-Ph CO2CH3 ..
~i 4-OCF3 4-C14-F-Ph CO2CH3 ;~.
~" 25 4-Br 4-C14-F-Ph CO2CH3 o 9-CF3 4-C14-F-Ph COCH2CH3 -~, 4-OCF3 4-C14-F-Ph 23 O
. 4-Br 4-C14-F-Ph COCH2CH3 :

~', 30 :;
., .~ .

:

Ji' ~ '~

'S ' ,'. ' ~:

_ 2~3$''.7~'~.'3 157 ~' TABLE 1~
Rl R 1 2 2 B A Ra 4-CF3 5-Ci H CHMe H H
9-OCF3 5-Cl H CHMe H H
4-Cl S-Cl H CHMe H H
; 4-Br 5-Cl H CHMe H H
4-OCF2H 5-Cl H CHMe H H
4-CF3 5-F H CHMe H H
4-OCF3 5-F H CHMe H H
4-C1 5-F H CHMe H
4-Br 5-F H CHMe H H
4-OCF2H 5-F H CHMe H H
i 4-CF3 5-Cl H CH(i-Pr) H H
4-C1 5-Cl H CH(i-Pr) H H ~
CF3 5-Cl Me CHMe H H ~ -OCF3 5-Cl Me CH(i-Pr) H H -OCF2H 5-Cl Me C(Me)2 H H
Cl 5-Cl Me C(Me)2 H H
' CF3 5-Cl CO2Me C(Me)2 H H
OCF3 5-Cl CO2Me C(Me)2 H H
OCF2H 5-Cl CO2Me CHEt H H
Cl 5-Cl CO2Me CHEt H H
CF3 5-F Ph CHMe H H
OCF3 5-F Ph CHMe H H
OCF2H 5-F Ph CHMe H H
, Cl 5-F Ph CHMe H H
CF3 5~P CO2Me CHMe H H
OCF3 5-F CO2Me CHMe H H
CF3 ~ H CH2 Me H
OCF3 H H CH2 Me CF3 H 4-F-Ph CH2 M~ R

OCF3 H 4-F-Ph CH2 Me H
CF3 5-Cl CO2Me CH2 Me H

.' .
.~ .

.: - .... ,-. ~ : : : . ~ : . : : .

Z~J~4~3 R2 B A R Ra OCF3 5-Cl CO2Me CH2 Me CF3 5-F CO2Me CH2 Me H
OCF3 5-F CO2Me CH2 Me H
CF3 5-Cl Me CR2 Me Me OCF3 5-Cl Me CH2 Me Me CF3 5-F Ph CH2 Me Me , OCP3 5-F Ph CH2 Me Me ~ 3 5-Cl C2Me CH2 Me Ne '- OCF3 5-Cl CO2Me CH2 Me Me ,~ 15 CF3 H H O Me H .
OCF3 H H O Ne H .
CF3 H H O Me Me OCF3 H H O Me Me ~'.
CF3 5-Cl CO2Me Me H ~
OCF3 5-Cl CO2Me O Me H ~.
. CF3 5-Cl CO2Me Me H ':
OCF3 5-Cl CO2Me O Me H
., CF3 5-F CO2Me O Me H
.,~ OCF3 5-F CO2Me O Me H .~.
::s 25 CF3 5-F Ph O Me H : ' S OCF3 5-F Ph O Me H
, CF3 5-F Me O Me H ~;
-, OCF3 5-F Me O Me H
CF3 H H S Me OCF3 H H S Me H
CF3 H Ph S Me H ~:
OCF3 5-Cl Ph S Me H
CF3 5-Cl ~ S Me ~e OCF3 5-Cl H S Me ~e CF3 5-F Me S Me H
OCF3 5-F Me S Me H

. ~ :

, ~\
2 ~ ~ ~ . 4 ~

R2 B A R~ Re OCF3 5-Cl H CH2 Me H
OCF3 5-Cl H CH2 Me H
CF3 ~-Cl H CH2 Me Me OCF3 5-Cl H CH2 Me Me CF3 5-F H CH2 Me Me OCF3 5-F H CH2 Me Me , :' ,~ , .
,~

~' ,.
`` .
~ 25 :
::

.,.' .
. :
, ,. :' .,, :~ ;
' 35 i, ;
~ :' , .

.. . .

2~$~

Formulation 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 the compounds of Formula I can be prepared in conventional ways. They include dusts, granules, pellets, solutions, suspensions, 10 emulsions, wettable powders, emulsifiable -concentrates, dry flowables and the like. Many of ;
these can be applied directly. gprayable 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 inter-mediates for further formulation. The formulations, broadly, contain about 1% to 99~ by weight of active ingredient(s) and at least one of a) about 0.1% to 20% surfactant(s) and b) about 5% to 99% solid or liquid diluent(s). More specifically, they will contain these ingredients in the following -; approximate proportions:
Percent by Weiaht Active In~redient Dilu~nt~s) $urfactant(s Wettable Powders 25-90 0-74 1-10 Oil Suspensions, 1-50 40-95 0-35 Emulsions, Solutions, (including Emulsifiable 30 Concentrates) Dusts 1-25 70-99 0-5 Granules and Pellets1-95 5-99 0 15 High Strength 90-99 0-10 0-2 Compositions ~' .
.~ .
, :
i.
:~
- . . . . .
.. . , . . , . - . - ~ ~ - , .
- . . ~. .. :, . . , . ~

. . . - . :- . :

Z~ 9 Lower or higher levels of active ingredient can, of course, be present depend;ng on the intended use S and the physical properties of the compound. Higher ratios of surfactant to active ingredient are some-times desirable, and are ach:;eved by incorporation into the formulation or by tank mi~ing.
Typical solid diluents are described in Watkins, et al., ~Handbook of Insecticide Dust Diluents and Carriersr, 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 stable against phase separation at O`C.
~McCutcheon~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 formula-tions can contain minor amounts of additives to reduce foam, caking, corrosion, microbiological 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 mi~ing the ingredients. Fine solid compositions are made by blending and, usually, qrinding as in a hammer or fluid energy mill. Suspensions are prepared by wet milling (see, for esample, U.S. 3,060,084). Granules ;~ and pellets can be made by spraying the active -~ 35 material upon preformed granular carriers or by agglomeration techniques. See Browning, ' ." , '. .

- . .. . .. : .
- . : . : - . - , . . . :
- : . ' ~ : ' - : :;: , .: ' , 2~3~4 ~
.

.~ ',"'.
~Agglomeration~, ~hemical Engi~eerina, December 4, 1967, pages 147 and following, and ~Perry's Chemical Engineer's Handbook , 4th Ed., McG.raw-Hill, New York, 1963, pages 8 to 59 and following.
Many of the compounds of the invention are most efficacious when applied in the form of an emulsifiable concentrate mised with a spray oil or spray oil concentrate. Although any oil can be used as a spray oil, spray oils usually have these chara~teristics: they are not phytoto~ic 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:
-Common Crop Oils U~d as Splay Qil~
Corn Oil Linseed Oil Cottonseed Oil Soybean Oil Coconut Oil Sunflower Oil Rapeseed Oil Olive Oil Peanut Oil Palm Oil - Safflower Oil Sesame Oil Mustardseed Oil Caster 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, l9B6.
E~amples of useful formulations of compounds of the present invention are as follows:

~ .
. .

. ~ . .

t E~am~le A
Emulsifiable Concentrat~
methyl 7-fluoro-3A,4-dihydro-2-[[[9-(trifluoro-methyl)-phenyl]amino]carbonyl]-3H-pyrazolo[5,1 -c]tl,4]benzo~azine-3a-carbo~ylate. 20%
blend of oil soluble sulfonates and polyo~yethylene 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 absence of any extraneous undissolved material in the product.
Example B
Wettable Powder methyl 7-fluoro-3A,4-dihydro-2-[tt4-(trifluoro-methyl)-phenyl]amino]carbonyl]-3H-pyrazolo[5,1 ~ 20 -c][1,4]benzoxazine-3a-carboxylate. 30%
- sodium alkylnaphthalenesulfonate 2%
sodium ligninsulfonate 2 synthetic amorphous silica 3%
~aolinite 63 The active ingredient is mi~ed with the inert materials in a blender. After grinding in a hammer-mill, the material is re-blended and sifted through a 50 mesh screen.

P~
Wettable powder of Example 8 10%
pyrophyllite (powder) 9o%
The wettable powder and the pyrophyllite diluent are thoroughly blended and then packaged. The product i5 suitable for use as a dust.
.~ ,: .
' , ., ,~,~. . .
.
~ ~, - - . - . . ~ - ... ,.. ,.... , ~ . . - .: ~

2 ~ g 3 ~ i ..`~L ~

Example Granul~
5 methyl 7-fluoro-3A,4-dihydro-2-[~t4-(trifluoro-methyl)-phenyl]amino]carbonyl]-3H-pyrazolo[5,1 -c][1,4]benzo~azine-3a-carboxylate. 10%
matter, 0.71/0.30 mm; U.S.S. No.
25-50 sieves) 90~
The active ingredient is dissolved in a volatile 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~am~le E
Granule Wettable powder of E~ample B 15%
gypsum 69%
potassium sulfate 16%
The ingredients are blended in a rotating mi~er and water sprayed on to accomplish granulation. 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 gran-ules are removed, dried, and screened. Oversize material is crushed to produce additional material in the desired range. These granules contain 4.5% active ingredient.
Example F
Solution methyl 7-fluoro-3A,4-dihydro-2-[tt4-(trifluoro-methyl)-phenyl]amino]
carbonyl]-3H-pyrazolot5,1-c][1,4]
benzo~azine-3a-carbosylate. 25%
N-methyl-pyrrolidone 75%
The ingredients are combined and stirred to produce a solution suitable for direct, low volume application.

-- . .
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. . ~

, - . . . ~; : .: :

"f.~
~ z~ 4 ~

E~amp.L~_~
Aq~eous Su~E~nsion Methyl 7-fluoro-3A,4-dihydro-2-[[[4-(trifluoro- methyl)-phenyl]amino3 ~arbonyl~-3H-pyrazolot5,1-c][1,4]
benzoxazine-3a~ca~boxylate. ~0%
polyacrylic acid thickener 0.3%
dodecyclophenol polyethylene glycol ` ether 0.5%
` disodium phosphate 1.0%
monosodium phosphate 0.5%
polyvinyl alcohol 1.0%
water 56.7%
The ingredients are blended and ground together ; in a sand mill to produce particles essentially all ; under 5 microns in size.
E~ample H
Oil Suspension Methyl 7-fluoro-3A,4-dihydro-2-[[[4-~trifluoro- methyl)-phenyl~amino]
carbonyl]-3H-pyrazolo[5,1-c][1,9]
benzo~azine-3a-carboxylate. 35.0%
blend of polyalcohol carbosylic 6.0%
esters and oil soluble petroleum sulfonates xylene range solvent 59.0%
; The ingredients are combined and ground together in a sand mill to produce particles essentially all below 5 microns. The product can be used directly, extended with oils, or emulsified in water.
Example I
~ait G~an~l~s Methyl 7-fluoro-3A,4-dihydro-2-tt[4-3.0%
(trifluoro- methyl)-phenyllamino]
carbonyl]-3H-pyrazolo[S,l-c~[1,4]

: .

... . ~, : .. . . . , . .:; ., , . . ,, . .... : ~ ; - : .

- ~ . .. . . .... ..
. . .... . . ~. ,.
. b ~

;~i?~ ,4 :' benzoxazine-3a-carbo~ylate.
blend of polyethosylated nonyl-9.0%
phenols and sodium dodecyl-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 can also be mi~ed with one or more other insecticides, fungicides, nematocides, bactericides, acaricides, or other biologically active '~ 15 compounds to form a multi-component pesticide giving - an even broader spectrum of effective agricultural - protection. Examples of other agricultural protectants with which compounds of the present invention can be ~- mixed or formulated are:
Insecticides:
;~ 3-hydroxy-N-methylcrotonamide(dimethylphosphate)ester (monocrotophos) methylcarbamic acid, ester with 2,3-dihydro-2,2-dimethyl-7-benzofuranol (carbofuran) 0-[2,4,5-trichloro-a-(chloromethyl)benzyl]phosphoric acid, 0',0'-dimethyl ester (tetrachlorvinphos) 2-mercaptosuccinic acid, diethyl ester, S-ester with thionophosphoric acid, dimethyl ester (malathion) phosphorothioic acid, 0,0-dimethyl, 0-~-nitrophenyl ester ~methyl parathion) methylcarbamic acid, ester with ~-naphthol (carbaryl) methyl O_(methylcarbamoyl)thiolacetohydro~amate (methomyl) N'-(4-chloro-o-tolyl)-N,N-dimethylformamidine~
(chlordimeform) 0,0-diethyl-0-(2-isopropyl-9-methyl-6-pyrimidylphos-phorothioate (diazinon) 'f : ~' ' " ' ' " ' ""' ' ' '.' "" ' ' ' ' ' ": . ' ' ' ` ~ . ' . ' . ' ' ' ',, ,' .:. ' ' . . ' . ' '' :
:
'` ' :

2't?~ L4 octachlorocamphene (toxaphene) O-ethyl O-~-nitrophenyl phenylphosphonothioate (EPN) (S)-a-cyano-m-phenOxybenzyl(lR,3R)-3-(2,2-dibromo-vinyl)-2,2-dimethylcyclopropanecarbo~ylate Sdelta-methrin3 Methyl N',N'-dimethyl-N-[~methylcarbamoyl)o~y]-l-thio-oxamimidate (o~amyl) cyano(3-pheno~yphenyl)-methyl-4-chloro-a-(l-meth ethyl)benzeneacetate (fenvalerate) (3-phenoxyphenyl)methyl(~ ~,trans-3-(2,2-dichloro-ethenyl)-2,2-dimethylcyclopropanecarboxylate (permethrin~
15a-cyano-3-pheno~ybenzyl 3-(2,2-dichlorovinyl)-2,2-: dimethylcyclopropane carboxylate (cypermethrin) O-ethyl-S-(P-chlorophenyl)ethylphosphonodithioate (profenofos) ; phosphorothiolothionic acid, O-ethyl-O-t4-(methylthio)-: 20phenyl]-S-n-propyl ester tsulprofos).
: , :
Additional insecticides are listed hereafter by their common names: triflumuron, diflubenzuron, ~ methoprene, buprofezin, thiodicarb, acephate, : 25 azinphos-methyl, chlorpyrifos, dimethoate, fonophos, isofenphos, methidathion, methamidiphos, monocrotophos, phosmet, phosphamidon, phosalone, pirimicarb, phorate, profenofos, terbufos, trichlorfon, metho~ychlor, bifenthrin, biphenate, cyfluthrin, fenpropathrin, fluvalinate, flucythrinate, tralomethrin, metaldehyde and rotenone.

methyl 2-benzimidazolecarbamate (carbendazim) tetramethylthiuram disulfide (thiuram) n-dodecylguanidine acetate (dodine) ; manganese ethylenebisdithiocarbamate (maneb) 1,4-dichloro-2,5-dimetho~ybenzene (chloroneb) 2~$ ~LL~t 3 methyl l-(butylcarbamoyl)-2-benzimidazolecarbamate (benomyl) 5 1-~2-(2,4-dichlorophenyl)-4-propyl-1,3-diosolan-2-ylmethyl]-lH-1,2,4-triazole (propiconazole) 2-cyano-N-ethylcarbamoyl-2-methoxyiminoacetamide (cymo~anil) 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-[ttbis(4-fluorophenyl)]tmethyl]silyl]methyl]-lH-1,2,4-triazole.
Nematocides:
S-methyl l-(dimethylcarbamoyl)-N-(methylcarbamoyloxy)-. thioformimidate S-methyl l-carbamoyl-N-(methylcarbamoyloxy)thioformimi-date N-isopropylphosphoramidic acid, 0-ethyl 0~-[4-(methyl-thio)-m-tolyl]diester (fenamiphos).
Bactericides:
. tribasic copper sulfate . streptomycin sulfate.
- 25 a~ricides:
senecioic acid, ester with 2-E~-butyl-4,6-dinitro-phenol (binapacryl) 6-methyl-1,3-dithiolo[4,5-c]quino~alin-2-one -~
(o~ythioquinox) 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 (hexythiazo~) ii , ,3 amitraz propargite fenbutatin-oxide bisclofentezin.
: Bioloqical ~acillus thuringiensis Avermectin B.
Utility The compounds of this invention e~hibit activity ~ against a wide spectrum of foliar and soil inhabiting : arthropods which are pests of growing and stored agronomic crops, forestry, greenhouse crops, ornamentals, nursery crops, stored food and fiber : products, livestock, household, and public and animal health. Those skilled in the art will recognize that ~ not all compounds are equally effective against all - 20 pests but the compounds of this invention display activity against:

larvae of the order Lepid~pt~L~ including fall and beet armyworm and other SpodQ~L~ spp., tobacco budworm, corn earworm and other H~liQthis spp., European :.
- corn borer, navel orangeworm, stalk/stem borers and other pyralids, cabbage and soybean loopers and other loopers, codling ` 30 moth, grape berry moth and other tortricids, black cutworm, spotted cutworm, other cutworms and other -~, '.
. -~ :

2~

, .
noctuids, diamondback moth, green cloverworm, velvetbean caterpillar, green cloverworm, pink bollworm, gypsy moth, and spruce budworm;

foliar feeding larvae and adults of the :
order Coleoptera including Colorado potato ~.
~0 beetle, Mesican bean beetle, flea beetle, Japanese beetles, and ~ther leaf beetles, boll weevil, rice water weevil, granary weevil, rice weevil and other weevil pests, a~d soil inhabiting insects such as Western corn rootworm and other ~L~brotica ~ spp., Japanese beetle, European chafer and ~ other coleopteran grubs, and wireworms;
,' :''.. ' adults and larvae of the orders Hemiptera and HompQ.tera including tarnished plant .
~ bug and other plant bugs (miridae), aster :6 leafhopper and other leafhoppers (cicadellidae), rice planthopper, brown .i planthopper, and other planthoppers i 25 (ful~oroid~), psylids, whiteflies :~ (ale4~Q~ ), aphids (a~hidae), scales (coc~id~ and diaspidi~), lace bugs iDgi~ tink bugs (~entatomidae)~
cinch bugs and other seed bugs 30 (lygae~ ), cicadas (cicadid~
spittlebugs (cercopids), sguash bugs . (coreidae), red bugs and cotton stainers ! (pyrrh~Q~

` 35 adults, larvae and eggs of the order acari (mites) including European red mite, two ; spotted spider mite, rust mites, McDaniel mite, and foliar feed mites;

~ Z~C~4 ~

, , adults and immatures of the order ~-Orthoptera including grasshoppers, adults and immatures of the order DiDtera : including leafminers, midges, fruit flies (tephritidae), and soil maggots;

adults and immatures of the order Thysa~Qp5~L~ including onion thrips and ; other foliar feeding thrips;

insect pests of the order Hymenoptera including carpenter ants, bees, hornets ::
.~ and wasps;
, .
. insect pests of the order Dip~L~
including house flies, stable flies, face .-, flies, horn flies, blow flies, and other muscoid fly pests, horse flies, deer flies '! and other Brachycera, mosquitoes, black ::
flies, biting midges, sand flies, sciarids, and other N~mato~ra:
` ! . . -insect pests of the order Ortho~tera including cockroaches and crickets; ~ ,~

'1;! 30 insect pests of the order Isoptera .
including the Eastern subterranean termite :~
and other termites;
!
-':-,. 35 ' ":

~':
J, . ~ . ., .

Z~ 4 9 ~.
insect pests of the order Mallopha~a and Anoplura including the head louse, body louse, chicken head louse and other sucking and chewing parasitic lice that attack man and animals;

insect pests of the order SiphonoDtera including the cat flea, dog flea and other fleas.

The specific species for which control is esemplified are: fall armyworm, SpodopteL~
~L~igi~e~d~; tobacco budworm, Heliothis vires~n~;
boll weevil, AnthQ~omus qrandis; aster leafhopper, ~Ys~ss~le~ f~scifrons; southern corn rootworm, Diabroti~ undecimpunct3ta. The pest control protection afforded by these compounds of the présent invention is not limited, however, to these species.

i ,. .. .
Applica~îQ~
Arthropod pests are controlled and protection of agronomic crops, animal and human health is achieved ~ 25 by applying one or more of the Formula I compounds of ; this invention, in an effective amount, to the locus of infestation, to the area to be protected, or ; directly on the pests to be controlled. Because of the diversity of habitat and ~ehavior of these 30 arthropod pest species, many different methods of application are employed. A preferred method of application is by spraying with equipment that distributes the compound in the environment of the v pests, on the foliage, animal, person, or pre~ise, in the soil or animal, to the plant part that is infested or needs to be protected. Alternatively, granular ` ~ ~

.,, ., ; , \ 2 ~ ~ r? ~ ~

formulations of these compounds can be applied to or 5 incorporated into the soil. Other methods of application can also be employed including direct and residual sprays, aerial, baits, eartags, boluses, foggers, aerosols, and many others.
The compounds of this invention can be applied 10 in their pure state, but most often application will be of a formulation comprising one or more compounds of this invention, with suitable carriers, diluents and surfactants depending on the contemplated end use. A preferred method of application involves 15 spraying a water dispersion of refined oil solution of the compounds. Combinations with spray oils, spray oil concentrations, and synergists such as piperonyl butoxide often enhance the efficacy of the compounds of Formula I.
The rate of application of the Formula I~ 2 compounds required for effective control will depend on such factors as the species of arthropod to be controlled, the pest's life cycle, life stage, its size, location, time of year, host crop or animal, 25 feeding behavior, mating behavior, ambient moisture, temperature, etc. In general, application rates of ` about 0.01 to 2 kg of active ingredient per hectare are sufficient to provide large-scale effective control of pests in agronomic ecosystems under normal 30 circumstances, but as little as 0.001 kg/hectare or as much as 8 kg/hectare may be required. For nonagronomic applications, effective use rates will range from about 0.1 to 5 mg/sguare foot but as little as 0.01 mg/square foot or as much as 15 mg/square foot 35 may be required~

,, ' .
~ .

.. , ~
, . , ' --- 2~3'1' 4'3 The following E~amples demonstrate the control efficacy of the compounds of Formula I on specific insect pests wherein Compounds 1 through 44 are described in Table 17 and Compounds 45 and 46 in Table 18; and Compound 47 in Table 19.
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.

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2 ~ L 4 9 .
~LE 1~

R25~<B , CON~ ~ ~

-.
. ' ~' ~.
CMPD ~1 B2 ~ Y B m.~.C
,~ 20 .
. .
1 4-CF3 H O H H 157.5-158.5 2 4-Cl H O H H 183-185 -~ 3 4-Br H O H H 200-202 ;~ 4 4-CF3 H O H Ph 183.S-185 ~'r 25 5 4-OCF2CF2H H O H Ph 190-191 6 4-Cl H O H Ph 186-188 - 7 4-CF3 H o H Me 186-187 .;
.;
~.i 8 4-I H O H Me 162-163.5 .
.. 9 4-COMe H O H Me 174-177 4-OCF2CF2H H O .H Me oil 11 4-CF3 H O H Ph 106-116 12 4-OCF3 5-Cl O H Ph 140-146 .: 13 4-CF3 S-F O H CO2Me 177-181.5 14 4-OCF3 5-F O H 4-C~-Ph 135-139 : 35 15 4-C1 5-F O H 4-Cl-Ph 190-191 16 4-CF3 5-F O H 4-Cl-Ph 80-84 ,' , ~ - .
.
,, ~

. .. .

2~ 4~

CMPD Bl ~ m.p.C

17 9-CF3 6-Cl O H Ph 215-215.5 18 4-C1 6-Cl O H Ph 180-181 i~ 19 4-Br 6-Cl O H Ph 173-175 4-CF3 H SO2 H Me 265-266 21 4-Cl H SO2 H Me 192-194 : 10 22 9-CF3 H S H Ph 238-240 23 4-CF3 H S H Me 188-189 24 4-Cl H S H Me 169-170 4-Br H S H Me 163-165 26 4-CF3 5-Cl O H 4-F-Ph178-179 27 9-CF3 5-Cl O Me 4-F-Ph155-156 28 4-OCF3 5-Cl O H 4-F-Ph110-112 :; 29 4-Br 5-Cl O H 4-F-Ph200-201 4-CF3 5-F O H Ph 176-178 31 4-Br 5-F O H Ph 162-163 32 4-C1 5-F O H Ph 192-193 33 4-OCF3 5-F O H Ph 79-81 ' 34 4-OCF3 5-Cl O H H 157-158 4-CF3 5-F O H Me 171-172 ': 36 4-Br 5-F O H Me 143-145 37 4-OCF3 5-F O H Me 124-126 . 38 4-OCF3 5-F O H H 138-139 4-CF3 5-F O Me H 158-160 41 4-CP3 5-Cl O ff H 171-172 . 30 92 4-Br 5-Cl O H H 177-179 . 44 4-Br 5-F O H H 182 183 :

2~ a~

S ~ ~
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.
;.
- 15 :

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... 45 CF3 H H H 219-221 46 CF3 Br H H 196-198 : .
~i TABLE l9 :.
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CMPQ Bl ~2 B Y m~p.oC :-47 C:F3 H CH3 H 215-217 ~.

,~

2~r~

EXAMPI.E_~
F~ll A~mYworm Test units, each consisting of an 8-ounce plastic cup containing a layer of wheat germ diet, approximately 0.5 cm thick, were prepared. Ten third-instar larvae of fall armyworm (spodQptera fru~iperda) 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 o three cups. Spraying wa~
accomplished by passing the cups, on a conveyer belt, directly beneath a flat fan hydraulic nozzle which - 15 discharged the spray at.a rate of 0.5 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 readings were taken. The results are tabulated ' 20 below.
Compound % Mortali~y ' .~ 11 100 , 25 14 100 .

.-. . , . . . , : ~
. . ; , : , .. . . . -, .:

EXAM~kE 7 To~acco Budwo~m The test procedure of E~ample 6 was repeated for efficacy against third-instar larvae of the tobacco budworm (Heliothis virescens) e~ept that mortality was assessed at 48 hours. The results are tabulated below.
, ':
Compound % Mortality lS 13 83 , .. . .

South~rn Corn RuQk~Lm Test units, each consisting of an 8-ounce 3C plastic cup containing 1 sprouted corn seed, were prepared. Sets of three test units were sprayed as described in E~ample 6 with individual solutions of the test compounds. After the spray on the cups had dried, five third-instar larvae of the southern corn rootworm (~ k~-otica undecimpuncta~ hQwa~i) were placed into each cup. A moistened dental wick was . ~.

. . .

.. , , .. . . , .. :.
'I ' '. ' ' ' . ; '~' ~ ' ~" Z~ a~

inserted into each cup to prevent drying and the cups were then covered. The cups were then held at 27~C
and 50% relative humidity for 48 hours, after which time mortality readings were taken. Of the compounds tests on Southern rootworm, the following tabulation depicts the activity:
Compound % Mortali~Y

13 100 ~ ' 100 '' 26 100 ' '' ~X~I$~_2 Boll,,Weevil ~ Five adult boll weevils (AnthonQm~s Qran-di~) ; were placed into each of a series of 9-ounce cups. ', The test procedure employed was then otherwise the same as in E~ample 6. Mortality readings were taken 48 hours after treatment. Of the compounds tested on boll weevil, the following tabulation depicts the activity:

.
' .', ....
:

2~r~ a ~

~ .
, . ~ .
. Comp~u~d % Mortality '~ 11 100 ~ ' lZ 100 .
13 93 ..

~. 32 100 . 15 EXAMPLE lQ
: Aster Leafhoppe~
~ Test units were prepared from a series of .
12-ounce cups, each containing oat (Avena.. sativa) seedlings in a l-inch layer of sterilized soil. The test units were sprayed as described in E~ample 6 with -. individual solutions of the below-listed compounds. -.
' After the oats had dried from the spraying, between 10 .~ and 15 adult aster leafhoppers (Mas~rosteles ..
fasc~frQn~) were aspirated into each of the covered ~i 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 tabulation depicts the . 3C activity:

sl 35 :
"

, ~ . , .: . , . ~ . . : .

Z~ 49 Compound~6 Mo rt a 1 i tv . 12 86 26 87 :

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.

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Claims (17)

1. A compound of the formula wherein:
Q is ; ;

; ;

; ;

;

G is O or S;
A is a 0, 1 or 2-atom bridge comprising 0 to 2 carbon atoms, 0 to 1 oxygen atoms, 0 to 1 S(O)q groups or 0 to 1 NR6 groups wherein each carbon atom is optionally substituted with 1 to 2 substituents selected from Ra;
B is H, C1 to C6 alkyl, C3 to C6 cycloalkyl optionally substituted with 1 to 2 halogens or 1 to 2 CH3, C4 to C6 cycloalkylalkyl, C1 to C6 haloalkyl, C2 to C6 alkenyl, C2 to C6 alkynyl, C2 to C6 alkoxyalkyl, C2 to C6 cyanoalkyl, C3 to C8 alkoxycarbonylalkyl, CO2R3, C(O)R3, C(O)NR3R4, C(S)NR3R4, C(S)R3, C(S)SR3, phenyl, phenyl substituted with (R5)p, benzyl, benzyl substituted with 1 to 3 -substituents independently selected from W, or OR7;
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;
R1, R2 and R5 are independently selected from R3, halogen, CN, N3, SCN, NO2, OR3, SR3, SOR3, SO2R3, OC(O)R3, OSO2R3, CO2R3 C(O)R3, C(O)NR3R4, SO2NR3R4, NR3R4, NR4C(O)R3, OC(O)NHR3, NR4C(O)NHR3 and NR4SO2R3, or when m, n or p is 2, R1, R2 or R5 can be -OCH2O-, -OCH2CH2O-, or -CH2CH2O-, each of which can be substituted with 1 to 4 halogen atoms or 1 to 2 methyl groups;

R3 is H, C1 to C6 alkyl, C1 to C6 haloalkyl, C2 to C6 alkenyl, C2 to C6 haloalkenyl, C2 to C6 alkynyl, C2 to C6 haloalkynyl, C2 to C6 alkoxyalkyl, C2 to C6 alkylthioalkyl, C1 to C6 nitroalkyl, C2 to C6 cyanoalkyl, C3 to C8 alkoaxycarbonylalkyl, C3 to C6 cycloalkyl, C3 to C6 halocycloalkyl, phenyl, benzyl, or phenyl or benzyl substituted with 1 to 3 substituents independently selected from W;
R4 is H, C1 to C4 alkyl or R3 and R4 can be taken together as (CH2)4, (CH2)5 or (CH2CH2OCH2CH2);
R6 is H, C1 to C4 alkyl, C1 to C4 haloalkyl, C2 to C4 alkenyl, C2 to C4 haloalkenyl, C2 to C4 alkynyl, 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;
Ra is independently selected from H, C1 to C6 alkyl, C2 to C4 alkolcycarbonyl and phenyl optionally substituted with 1 to 3 substi-tuents independently selected from W;
X is O or S:
n is 1 to 2;
m is 1 to 3;
p is 1 to 3;
q is 0 to 2;

Y is H, C1 to C6 alkyl, C2 to C6 alkoxyalkyl, CHO, C2 to C6 alkylcarbonyl, C2 to C6 alkoxycarbonyl, C2 to C6 haloalkylcarbonyl, C1 to C6 alkylthio, C1 to C6 haloalkylthio, phenylthio, phenylthio substituted with 1 to 3 substituents independently selected from W, or S-J;
J is NR8?R9, NR8S(O)tR9, ?R9 NR8R12 or SR10 R8 and R12 are independently selected from C1 to C6 alkyl, C1 to C6 haloalkyl, C3 to C6 cycloalkyl, C4 to C7 cycloalkylalkyl, phenyl optionally substituted with 1 to 2 substi-tuents independently selected from W, benzyl optionally substituted with 1 to 2 substituents independently selected from W, phenethyl optionally substituted with 1 to 2 substituents independently selected from W, C2 to C6 cyanoalkyl, C2 to C6 alkoxyalkyl, C3 to C8 alkoxycarbonylalkyl and C4 to C8 di-alkylaminocarbonylalkyl, 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, C1 to C6 haloalkyl, Cl to C22 alkoxy, C2 to C8 dialkylamino, piperidinyl, pyrollidinyl, morpholino, C1 to C4 haloalkoxy, C1 to C4 alkoxy substituted with cyano, nitro, C2 to C4 alkoxy, C4 to C8 alkoxyalkoxy, C1 to C2 alkylthio, C2 to C3 alkoxycarbonyl, C3 to C5 dialkylaminocarbonyl or phenyl, or R9 is phenyl optionally substi-tuted with 1 to 2 substituents independently selected from W, or phenoxy optionally substituted with 1 to 2 substituents independently selected from W;
R10 and R11 are independently selected from C1 to C4 alkyl, C2 to C4 haloalkyl and phenyl optionally substituted with 1 to 2 substi-tuents independently selected from W, or R10 and R11 can be taken together as (CH2)2, (CH2)3 or CH2C(CH3)2CH2;
t is 0 to 2; and Y1 is O or S.

2. A compound according to Claim 1 wherein:
A is CRaRa, S, O or NR6;
B is H, C1 to C6 alkyl, C1 to C6 haloalkyl, C2 to C6 alkenyl, C2 to C6 alkynyl, C2 to C6 alkoxyalkyl, C3 to C8 alkoxycarbonylalkyl, CO2R3, C(O)R3, C(O)NR3R4, C(S)NR3R4, C(S)R3, C(S)SR3, phenyl or phenyl substituted by (R5)p;
W is Cl, F, Br, CN, CF3, C1 to C2 alkyl, C1 to C2 alkoxy, OCF2H, OCF3 or NO2;
R2 is R3, halogen, CN, SCN, NO2, OR3 or SR3;
R3 is H, Cl to C4 alkyl, Cl to C2 haloalkyl, C3 to C4 alkenyl, C3 to C4 haloalkenyl, propargyl, phenyl, benzyl, or phenyl or benzyl substituted with one of F, Cl, Br, CF3, OCF3, OCF2H or NO2;
p is 1 or 2;

m is 1 or 2;
X is 0;
Y is H, C1 to C4 alkyl, SCH3, SCCl3, SO2CH3, SC6H5, 2-NO2-C6H4S, C(O)CH3, C(O)CH2CH3, C(O)CF3; CO2CH3, CO2CH2CH3, or S-J;
J is J1, J2, J3, J4 or J5;
R8 and R12 are independently selected from C1 to C6 alkyl, C1 to C6 haloalkyl, C5 to C6 cycloalkyl, C3 to C8 alkoxycarbonylalkyl, phenyl, benzyl and phenethyl, each phenyl, benzyl and phenethyl optionally 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 selected from C1 to C3 alkyl or phenyl; and t is 2.

3. A compound according to Claim 2 wherein:
B is H, C1 to C4 alkyl, C3 to C4 alkoxycarbonyl-alkyl, CO2R3, C(O)R3, phenyl or phenyl substituted with (R5)p;
R1 is halogen, CN, SCN, NO2, OR3, SR3, SO2R3, CO2R3, C(O)R3 or is R3 with one substituent in the 4-position;
R5 is H, R3, halogen, CN, SCN, NO2, OR3, SR3, SO2R3, C(O)R3, OSO2R3, CO2R3, C(O)R3, C(O)NR3R4, SO2NR3R4 or NR3R4; or, when m or p is 2;
R1 and R5 can be taken together as -CH2C(CH3)2O-, OCH2CH2O-, OCF2CF2O- or -CF2CF2O- to form a 5- or 6-membered fused ring;
R3 is C1 to C4 alkyl, C1 to C2 haloalkyl, C3 to C4 alkenyl or propargyl;
R4 is H or CH3;
Ra is H, CH3, CO2CH3 or CO2CH2CH3;

m and p are independently 1 or 2 and one substi-tuent is in the para-position;
Y is H, CH3, COCH3, CO2CH3 or S-J;
J is J1 or J2;
R8 is C1 to C4 alkyl or phenyl optionally substi-tuted with C1 or CH3;
R9 is C1 to C20 alkyl, C1 to C20 alkoxy, C1 to C6 haloalkyl, dimethylamino, phenyl option-ally substituted with Cl or CH3, or, R9 is C1 to C4 alkoxy substituted with C2 to C4 alkoxy or 1 to 6 halogens; and G is S.

4. A compound according to Claim 3 wherein:
R1 is Cl, F, Br, CF3, CN, OCF3, OCF2H, OCF2CF2H
or SCF2H;
R2 and R5 are independently H, Cl, F, Br, CN, CF3, CH3, OCH(CH3)2, OCF2H, OCF3, SCH3, SCF2H, NO2 or OCH2CF3;
B is H, CH3, CH2CH3, CH(CH3)2, CO2CH3, CO2CH2CH3, phenyl or phenyl substituted with (R5)p; and Ra is H or CH3.

5. A compound according to Claim 4 wherein:
A is O or CH2.

6. A compound according to Claim 5 wherein:
Q is Q-1.

7. A compound according to Claim 5 wherein:
Q is Q-2.

8. A compound according to Claim 5 wherein:
Q is Q-3,

9. A compound according to Claim 5 wherein:
Q is Q-4.

10. A compound according to Claim 5 wherein:
Q is Q-5.

11. A compound according to Claim 5 wherein:
Q is Q-6.

12. A compound according to Claim 5 wherein:
Q is Q-7.

13. A compound according to Claim 6 which is:
methyl 3,3a,4,5-tetrahydro-2-[[[4-trifluoro-methyl)pheny]-amino]carbonyl]-2H-pyrazolo[3,-4-f]-quinoline-3a-carboxylate.

14. A compound according to Claim 9 which is:
methyl 3,3a,4,5-tetrahydro-2-[[[4-trifluoro-methyl)phenyl]-amino]carbonyl]-2H-pyrazolo[4,-3-h]-quinoline-3a-carboxylate.

15. A compound according to Claim 10 which is:
methyl 7-chloro-3,3a,4,5-tetrahydro-N-[[[4-trifluoromethyl)phenyl]amino]carbonyl]-2H-thieno [2,3-g]-indazole-3a-carboxylate.

16. An arthropodicidal composition comprising an arthropodicidally effective amount of a compound according to any one of Claims 1 to 15 and a carrier therefor.

17. A method for controlling arthropods comprising applying to them or their environment an arthropodicidally effective amount of a compound according to any one of Claims 1 to 15.