Synthesis of N-aryl benzamides containing pharmacophoric tyrosine kinase inhibitor fragments

Article abstract of DOI:10.1134/S1070428015010182

New N-aryl 4-(arylaminomethyl)benzamides containing pharmacophoric heterocyclic fragments have been synthesized from 2-arylaminopyrimidine, 1-methylpiperazine, and morpholine derivatives and substituted benzoic acids.

Full text of DOI:10.1134/S1070428015010182

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2015, Vol. 51, No. 1, pp. 101–109. © Pleiades Publishing, Ltd., 2015.
Original Russian Text © E.V. Koroleva, Zh.V. Ignatovich, K.N. Gusak, A.L. Ermolinskaya, Yu.V. Sinyutich, 2015, published in Zhurnal Organicheskoi
Khimii, 2015, Vol. 51, No. 1, pp. 104–111.
Synthesis of N-Aryl Benzamides Containing Pharmacophoric
Tyrosine Kinase Inhibitor Fragments
E. V. Koroleva, Zh. V. Ignatovich, K. N. Gusak, A. L. Ermolinskaya, and Yu. V. Sinyutich
Institute of New Materials Chemistry, National Academy of Sciences of Belarus,
ul. F. Skoriny 36, Minsk, 220141 Belarus
e-mail: evk@ichnm.basnet.by
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Scheme 1.
Me
Me
N
N
N
H2N
N
H
N
H2N
N
N
H2N
N
N
H
H
N
N
N
1
2
3
NH2
O2N
Me
NH2
O2N
NH2
Me
O2N
CF3
5
6
7
O
Me
O
N
K3PO4 or K2CO3, THF
Cl
a:
1 +
N
N
H
N
Cl
H
Cl
N
4, 88%
Me
O
N
5, 6, DMF (pyridine)
125–130°C
N
N
H
N
H
H
N
N
R1
12 (21%), 13 (77%)
O
N
O
OH
N
O
N
(1) MeOC(O)C6H4CHO
NaBH(OAc)3
OH
(HOBt)
N
H
(2) H+/H2O
N
N
b:
6, 7
R1
HN
N
R1
8, 9
10, 11
N
N
N
N
N
N
Me
1–3, DCC, Et3N
DMF, 0–20°C
N2H4· H2O, Raney Ni
MeOH, 60–65°C
R2
R2
R1
NH
NH
HN
HN
NH2
R3
R3
HN
HN
O
13 (71%), 14 (88%), 16 (90%), 18 (53%)
O
15 (77%), 17 (63%)
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57=8Fꢂ 8ꢆꢂ 9ꢆꢂ5A8ꢂ 29ꢂJ=G<ꢂꢇꢈꢉꢇꢈ5@=AB69AML?ꢊꢈꢀꢈ@9G<L?ꢈ
,<9ꢂFGEH7GHE9ꢂB:ꢂG<9ꢂ=FB?5G98ꢂ7B@CBHA8FꢂJ5Fꢂ
ꢀ
7BA:=E@98ꢂ6LꢂG<9=Eꢂ9?9@9AG5?ꢂ5A5?LF9Fꢂ5A8ꢂ!*ꢆꢂ ꢂ5A8ꢂ
ꢀꢌꢍꢂ&%*ꢆꢂ5A8ꢂ@5FFꢂFC97GE5 ꢂ,<9ꢂ@B?97H?5Eꢂ=BAꢂC95>Fꢂ
Scheme 2.
H
O
N
N
N
NH
Me
6
Me
NO2
N
N
H
20, 44%
NH2
H
O
N
N
N
NH
NO2
Me
NO2
N
O
OH
N
N
H
DCC, HOBt, Et3N
DMF, 0–20°C
N
NH
21, 84%
Me
NO2
N
H
NH2
NO2
O
N
N
N
H
19
N
NH
Me
N
N
H
22
Me
N
O
N
Me
N
N
HN
N
Me
NH
N
N
H
23, 66%
*-++!ꢃ&ꢂꢂ"'-*&ꢃ$ꢂꢂ'ꢎꢂꢂ'*ꢗꢃ&!ꢍꢂꢂꢍ ꢘ%!+,*1ꢂꢂꢂ.B? ꢂꢂꢓꢀꢂꢂꢂ&B ꢂꢂꢀꢂꢂꢂꢄꢁꢀꢓꢂ

#'*'$ꢘ.ꢃꢂꢂ9Gꢂ5? ꢂ
ꢀꢁꢇꢂ
Scheme 3.
O
H2N
Me
HOBt, DCC
N
H
N
8, 9
+
N
N
R
H
N
N
Me
24
25 (77%), 26 (82%)
Me
O
(1) SOCl2; (2) 6
O
N
H
NO2
N
27, 95%
O
N
(1) SOCl2; (2) 24
N
O
N
H
Me
O
N
O
OH
28, 70%
N
O
N
29
HOBt, 2, DCC
O
N
H
N
N
N
N
H
N
30, 84%
Me
O
N
(1) SOCl2; (2) 3
O
N
H
N
H
N
N
31, 73%
25ꢆꢂ*ꢂꢙꢂꢄꢈ%9ꢈꢓꢈ'ꢄ&ꢋꢂ26ꢆꢂ*ꢂꢙꢂꢌꢈ'ꢄ&ꢈꢇꢈ%9 ꢂ
3M4ꢚꢂꢉIE9?ꢂꢄPꢌꢅꢐꢊꢂ=AꢂG<9ꢂ@5FFꢂFC97GE5ꢂJ9E9ꢂ7BAF=FG9AGꢂ
J=G<ꢂG<9ꢂ5FFH@98ꢂ:BE@H?5F ꢂ ,<9ꢂ!*ꢂFC97GE5ꢂB:ꢂG<9ꢂ
FLAG<9F=M98ꢂ5@=89Fꢂ7BAG5=A98ꢂ56FBECG=BAꢂ65A8Fꢂ8H9ꢂGBꢂ
12P17ꢆꢂ 21P23ꢆꢂ 25P28ꢆꢂ5A8ꢂ 31ꢂ5?FBꢂ8=FC?5L98ꢂBA9ꢂBEꢂ
GJBꢂF=A;?9GFꢂ5Gꢂ δꢂꢄ ꢁꢓPꢄ ꢕꢄ CC@ꢂ:EB@ꢂCEBGBAFꢂ=AꢂG<9ꢂ
@9G<L?ꢂ;EBHCF ꢂ,<9ꢂCE=@5ELꢂ5@=ABꢂ;EBHCꢂ=Aꢂ 15ꢂ5A8ꢂ17ꢂ
FGE9G7<=A;ꢂI=6E5G=BAFꢂB:ꢂG<9ꢂ& ꢂꢉꢌꢓꢁꢁPꢌꢇꢌꢁꢂ7@ Pꢀꢊꢂ5A8ꢂ ;5I9ꢂ5ꢂ6EB589A98ꢂGJBꢈCEBGBAꢂF=A;?9Gꢂ=AꢂG<9ꢂE9;=BAꢂ
5@=89ꢂ75E6BAL?ꢂ;EBHCFꢂꢉꢀꢒꢅꢁPꢀꢒꢔꢁꢂ7@ Pꢀꢊꢂ5A8ꢂ69A8=A;ꢂ δꢂꢇ ꢁꢁPꢇ ꢓꢁ CC@ꢆꢂ5A8ꢂF=;A5?Fꢂ:EB@ꢂ5EB@5G=7ꢂCEBGBAFꢂ=Aꢂ
I=6E5G=BAFꢂB:ꢂG<9ꢂ5@=89ꢂ& ꢂ;EBHCꢂꢉꢀꢒꢔꢁPꢀꢒꢕꢁꢂ7@Pꢀꢊ ꢂꢂ
G<9ꢂ69AM9A9ꢂE=A;ꢂ5GG57<98ꢂGBꢂG<5Gꢂ5@=ABꢂ;EBHCꢂJ9E9ꢂ
?B75G98ꢂ=Aꢂ5ꢂFGEBA;9Eꢂ:=9?8ꢂE9?5G=I9ꢂGBꢂG<9ꢂ7BEE9FCBA8=A;ꢂ
F=;A5?FꢂB:ꢂG<9ꢂ=A=G=5?ꢂA=GEBꢂ7B@CBHA8
!AꢂG<9ꢂ ꢀ ꢂ&%*ꢂFC97GE5ꢆꢂ& ꢂCEBGBAꢂF=;A5?Fꢂ5Cꢈ
C95E98ꢂ5FꢂF=A;?9GFꢂ5Gꢂ δꢂꢒ ꢀꢁPꢔ ꢔꢁꢂꢉ5@=A9ꢊꢂ5A8ꢂꢔ ꢁꢌP
ꢀꢁ ꢀꢁꢂCC@ꢂꢉ5@=89ꢊꢆꢂJ<BF9ꢂ CBF=G=BAꢂ89C9A898ꢂBAꢂG<9ꢂ
FB?I9AG ꢂꢃEB@5G=7ꢂCEBGBAFꢂ=AꢂG<9ꢂ69AM9A9ꢆꢂCLE=@=8=A9ꢆꢂ
5A8ꢂCLE=8=A9ꢂE=A;FꢂE9FBA5G98ꢂ=AꢂG<9ꢂE9;=BAꢂ δꢂꢒ ꢁPꢂ
ꢅ ꢁꢂCC@ꢆꢂ5A8ꢂ69AML?=7ꢂꢍ ꢄꢂCEBGBAFꢂ;5I9ꢂF=;A5?Fꢂ5Gꢂꢂ
δꢂꢇ ꢄPꢇ ꢒꢂCC@ꢆꢂJ<=7<ꢂ=Aꢂ@BFGꢂ75F9FꢂJ9E9ꢂFC?=Gꢂ8H9ꢂGBꢂ
7BHC?=A;ꢂJ=G<ꢂG<9ꢂ& ꢂCEBGBAꢂꢉ δꢂꢓ ꢔPꢒ ꢅꢂCC@ꢆꢂGꢆꢂ Jꢂꢙꢂ
ꢓ ꢓPꢒ ꢔꢂ Mꢊ ꢂ,<9ꢂꢍ ꢄꢂF=;A5?ꢂ=AꢂG<9ꢂFC97GE5ꢂB:ꢂ 25P28ꢂ
J5FꢂABGꢂFC?=Gꢂ=:ꢂABꢂ& ꢂF=;A5?ꢂJ5FꢂB6F9EI98ꢂ8H9ꢂGBꢂ:5FGꢂ
,<9ꢂꢀꢌꢍꢂ&%*ꢂFC97GE5ꢂ7BAG5=A98ꢂ5ꢂF=;A5?ꢂ5Gꢂꢂ
δꢍꢂꢀꢒꢓ ꢁꢁPꢀꢕꢓ ꢁꢁꢂCC@ꢆꢂJ<=7<ꢂJ5FꢂABGꢂB6F9EI98ꢂ=AꢂG<9ꢂ
ꢑꢘ(,ꢂFC97GEH@ꢆꢂ=A8=75G=A;ꢂG<9ꢂCE9F9A79ꢂB:ꢂ5ꢂ75E6BAL?ꢂ
;EBHC ꢂ+=;A5?Fꢂ:EB@ꢂ75E6BAꢂ5GB@Fꢂ=AꢂG<9ꢂ@BEC<B?=A9ꢂ
5A8ꢂC=C9E5M=A9ꢂ:E5;@9AGFꢂB:ꢂ25ꢆꢂ28ꢆꢂ30ꢆꢂ5A8ꢂ31ꢆꢂ5FꢂJ9??ꢂ
5Fꢂ:EB@ꢂG<9ꢂꢍ ꢄꢂ;EBHCꢆꢂJ9E9ꢂ?B75G98ꢂ=AꢂG<9ꢂE9;=BAꢂꢂ
δꢍꢂꢇꢒPꢒꢌꢂCC@ꢂ5A8ꢂJ9E9ꢂ8=F7E=@=A5G98ꢂ=AꢂG<9ꢂꢑꢘ(,ꢂ
FC97GEH@ ꢂ,<9ꢂ@9G<L?ꢂ75E6BAꢂ5GB@Fꢂ=Aꢂ 12P18ꢆꢂ21P23ꢆꢂ
ꢖꢑꢂ9K7<5A;9ꢂJ=G<ꢂG<9ꢂ89HG9E5G98ꢂFB?I9AG ꢂꢍB@CBHA8Fꢂ 25P28ꢆꢂ5A8ꢂ31ꢂE9FBA5G98ꢂ5Gꢂδꢍꢂꢀꢒ ꢁPꢄꢀ ꢁꢂCC@ ꢂ
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ꢕ ꢁꢂ Mꢊꢆꢂꢔ ꢇꢓꢂ8ꢂꢉꢀ ꢆꢂ Jꢂꢙꢂꢓ ꢀꢂ Mꢊꢆꢂꢔ ꢒꢄꢂDꢂꢉꢀ ꢆꢂ Jꢂꢙꢂꢂ
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δꢍꢆꢂCC@ꢛꢂꢀꢕ ꢇꢇꢆꢂꢇꢓ ꢄꢀꢆꢂꢀꢁꢕ ꢌꢁꢆꢂꢀꢀꢒ ꢇꢅꢆꢂꢀꢀꢒ ꢅꢓꢆꢂꢀꢄꢌ ꢓꢓꢆꢂ
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J9E9ꢂ58898ꢆꢂ5A8ꢂG<9ꢂ@=KGHE9ꢂJ5FꢂFG=EE98ꢂ:BEꢂꢅꢂ<ꢂ5Gꢂꢂ
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{4-methyl-3-[4-(pyridin-3-yl)pyrimidin-2-ylamino]-
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Tꢓꢂ@$ꢊ ꢂ,<9ꢂ
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ꢌ ꢔꢂ Mꢊꢆꢂꢔ ꢅꢇꢂFꢂꢉꢀ ꢊꢆꢂꢅ ꢄꢇꢂFꢂꢉꢀ ꢊꢆꢂꢀꢁ ꢀꢌꢂFꢂꢉꢀ ꢊ ꢂꢂ
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ꢓꢓ ꢒꢓꢆꢂꢀꢁꢄ ꢌꢀꢆꢂꢀꢁꢕ ꢀꢒꢆꢂꢀꢀꢁ ꢀꢅꢆꢂꢀꢀꢒ ꢕꢔꢆꢂꢀꢄꢌ ꢒꢇꢆꢂꢀꢄꢒ ꢌꢁꢆꢂ
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ꢀꢌꢇ ꢒꢄꢆꢂꢀꢌꢒ ꢕꢅꢆꢂꢀꢌꢕ ꢌꢒꢆꢂꢀꢇꢄ ꢕꢓꢆꢂꢀꢇꢒ ꢇꢔꢆꢂꢀꢇꢒ ꢓꢓꢆꢂ
ꢀꢇꢕ ꢌꢓꢆꢂꢀꢓꢁ ꢇꢅꢆꢂꢀꢓꢒ ꢄꢔꢆꢂꢀꢓꢅ ꢀꢌꢆꢂꢀꢒꢁ ꢕꢒꢆꢂꢀꢒꢀ ꢁꢄꢆꢂ
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Tꢌꢁꢂ@$ꢊꢆꢂ5A8ꢂE97ELFG5??=M98ꢂ
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{4-methyl-3-[4-(pyridin-3-yl)pyrimidin-2-ylamino]-
phenyl}benzamide (13).ꢂ1=9?8ꢂꢕꢀꢐ ꢂ
4-[(4-Methyl-3-nitrophenylamino)methyl]-N-
{3-[4-(pyridin-3-yl)pyrimidin-2-ylamino]phenyl}-
benzamide (14).ꢂ1=9?8ꢂꢔꢔꢐꢆꢂL9??BJꢂ7ELFG5?Fꢆꢂ@CꢂꢄꢁꢅP
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ꢀ
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ꢀꢀꢔ ꢒꢅꢆꢂꢀꢄꢌ ꢒꢒꢆꢂꢀꢄꢒ ꢕꢒꢆꢂꢀꢄꢕ ꢒꢔꢆꢂꢀꢄꢔ ꢄꢄꢆꢂꢀꢌꢀ ꢅꢓꢆꢂ
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N-(4-Methyl-3-nitrophenyl)-4-{4-methyl-3-
[4-(pyridin-3-yl)pyrimidin-2-ylamino]phenylamino-
methyl}benzamide (20).ꢂ1=9?8ꢂꢇꢇꢐꢆꢂ?=;<GꢂL9??BJꢂ
7ELFG5?Fꢆꢂ@CꢂꢀꢒꢔPꢀꢕꢁRꢍ ꢂ!*ꢂFC97GEH@ꢂꢉ#ꢏEꢊꢆꢂν ꢆꢂ7@Pꢀꢛꢂ
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ꢉꢄ ꢆꢂ Jꢂꢙꢂꢔ ꢄꢂ Mꢊ ꢂ ꢀꢌꢍꢂ&%*ꢂFC97GEH@ꢂꢉꢍꢑ 'ꢑꢊꢆꢂ δꢍꢆꢂ
ꢌ
CC@ꢛꢂꢀꢕ ꢅꢇꢆꢂꢇꢓ ꢀꢇꢆꢂꢓꢄ ꢓꢅꢆꢂꢓꢓ ꢄꢄꢆꢂꢒꢄ ꢔꢀꢆꢂꢒꢇ ꢀꢅꢆꢂꢀꢁꢇ ꢓꢀꢆꢂ
ꢀꢀꢄ ꢁꢔꢆꢂꢀꢄꢀ ꢅꢕꢆꢂꢀꢄꢕ ꢅꢕꢆꢂꢀꢄꢔ ꢔꢒꢆꢂꢀꢌꢁ ꢅꢁꢆꢂꢀꢌꢀ ꢁꢅꢆꢂ
ꢀꢌꢀ ꢄꢓꢆꢂꢀꢌꢌ ꢅꢕꢆꢂꢀꢌꢇ ꢅꢕꢆꢂꢀꢌꢅ ꢄꢀꢆꢂꢀꢇꢇ ꢅꢄꢆꢂꢀꢇꢔ ꢀꢁꢆꢂ
ꢀꢇꢔ ꢕꢌꢆꢂꢀꢒꢔ ꢕꢀ ꢂꢎBHA8ꢆꢂꢐꢛꢂꢍꢂꢒꢔ ꢓꢌꢋꢂ ꢂꢒ ꢓꢔꢋꢂ&ꢂꢀꢇ ꢓꢔ ꢂ
ꢍꢄꢕ ꢌꢀ&ꢓ'ꢌ ꢂꢍ5?7H?5G98ꢆꢂꢐꢛꢂꢍꢂꢒꢔ ꢇꢔꢋꢂ ꢂꢒ ꢒꢁꢋꢂ&ꢂꢀꢇ ꢕꢅ ꢂ
4-{4-Methyl-3-[4-(pyridin-3-yl)pyrimidin-2-yl-
amino]phenylaminomethyl}-N-(3-nitrophenyl)benz-
amide (21).ꢂ1=9?8ꢂꢔꢇꢐꢆꢂ?=;<Gꢂ6EBJAꢂ7ELFG5?Fꢆꢂ@CꢂꢄꢅꢓP
ꢌꢁꢁRꢍ ꢂ!*ꢂFC97GEH@ꢂꢉ#ꢏEꢊꢆꢂ νꢆꢂ7@PꢀꢛꢂꢌꢇꢇꢌPꢌꢀꢕꢓꢆꢂꢀꢕꢁꢇꢆꢂ
ꢀ
ꢀꢒꢇꢁꢆꢂꢀꢓꢓꢔꢆꢂꢀꢇꢀꢓ ꢂ ꢂ&%*ꢂFC97GEH@ꢂꢉꢑ%+'ꢈ dꢒꢊꢆꢂδꢆꢂ
4-[(4-Methyl-3-nitrophenylamino)methyl]-N-
{4-[(4-methylpiperazin-1-yl)methyl]phenyl}benz-
amide (26).ꢂ1=9?8ꢂꢔꢄꢐꢆꢂL9??BJꢂ7ELFG5?Fꢆꢂ@CꢂꢀꢕꢀPꢂ
ꢀꢕꢌRꢍ ꢂ!*ꢂFC97GEH@ꢂꢉ#ꢏEꢊꢆꢂν ꢆꢂ7@Pꢀꢛꢂꢌꢇꢇꢁꢆꢂꢌꢄꢔꢁꢆꢂꢀꢒꢓꢀꢆꢂ
CC@ꢛꢂꢄ ꢁꢕꢂFꢂꢉꢌ ꢊꢆꢂꢇ ꢇꢒꢂ8ꢂꢉꢄ ꢆꢂ Jꢂꢙꢂꢒ ꢌꢂ Mꢊꢆꢂꢒ ꢀꢇꢂGꢂꢉꢀ ꢆꢂ
Jꢂꢙꢂꢒ ꢌꢂ Mꢊꢆꢂꢒ ꢌꢓꢂ8 8ꢂꢉꢀ ꢆꢂJꢂꢙꢂꢔ ꢄꢆꢂꢄ ꢌꢂ Mꢊꢆꢂꢒ ꢒꢀꢂ8ꢂꢉꢀ ꢆꢂ
Jꢂꢙꢂꢄ ꢔꢂ Mꢊꢆꢂꢒ ꢔꢓꢂ@ꢂꢉꢄ ꢊꢆꢂꢕ ꢇꢁꢂ8ꢂꢉꢀ ꢆꢂ Jꢂꢙꢂꢔ ꢇꢂ Mꢊꢆꢂꢂ
ꢕ ꢇꢒꢂ8ꢂꢉꢀ ꢆꢂJꢂꢙꢂꢕ ꢅꢂ Mꢊꢆꢂꢕ ꢇꢔꢂ8ꢂꢉꢄ ꢆꢂJꢂꢙꢂꢔ ꢄꢂ Mꢊꢆꢂꢕ ꢓꢇꢂFꢂ
ꢉꢀ ꢊꢆꢂꢕ ꢅꢀꢂ8ꢂꢉꢄ ꢆꢂ Jꢂꢙꢂꢔ ꢄꢂ Mꢊꢆꢂꢔ ꢁꢄꢂ8 8ꢂꢉꢀ ꢆꢂ Jꢂꢙꢂꢔ ꢌꢆꢂ
ꢄ ꢇꢂ Mꢊꢆꢂꢔ ꢇꢓPꢔ ꢓꢕꢂ@ꢂꢉꢄ ꢊꢆꢂꢔ ꢕꢁꢂFꢂꢉꢀ ꢊꢆꢂꢔ ꢕꢄꢂ8ꢂꢉꢀ ꢆꢂꢂ
Jꢂꢙꢂꢓ ꢕꢂ Mꢊꢆꢂꢅ ꢀꢄꢂ8ꢂꢉꢀ ꢆꢂJꢂꢙꢂꢀ ꢕꢂ Mꢊꢆꢂꢀꢁ ꢇꢁꢂFꢂꢉꢀ ꢊ ꢂꢂ
ꢀꢌꢍꢂ&%*ꢂFC97GEH@ꢂꢉꢑ%+'ꢈdꢒꢊꢆꢂδꢍꢆꢂCC@ꢛꢂꢀꢔ ꢀꢄꢆꢂꢇꢒ ꢄꢒꢆꢂ
ꢀꢁꢕ ꢄꢀꢆꢂꢀꢁꢔ ꢇꢄꢆꢂꢀꢁꢅ ꢌꢕꢆꢂꢀꢀꢓ ꢁꢁꢆꢂꢀꢀꢔ ꢓꢅꢆꢂꢀꢄꢌ ꢒꢔꢆꢂ
ꢀꢄꢇ ꢇꢌꢆꢂꢀꢄꢒ ꢓꢒꢆꢂꢀꢄꢕ ꢁꢁꢆꢂꢀꢄꢕ ꢀꢇꢆꢂꢀꢌꢅ ꢕꢀꢆꢂꢀꢌꢄ ꢌꢄꢆꢂ
ꢀꢌꢄ ꢔꢄꢆꢂꢀꢌꢌ ꢔꢌꢆꢂꢀꢌꢕ ꢓꢓꢆꢂꢀꢌꢕ ꢅꢀꢆꢂꢀꢇꢇ ꢀꢅꢆꢂꢀꢇꢒ ꢌꢀꢆꢂ
ꢀꢇꢕ ꢒꢄꢆꢂꢀꢇꢔ ꢀꢓꢆꢂꢀꢓꢀ ꢀꢇꢆꢂꢀꢓꢔ ꢅꢀꢆꢂꢀꢒꢁ ꢓꢓꢆꢂꢀꢒꢀ ꢀꢄꢆꢂ
ꢀꢒꢔ ꢁꢒ ꢂꢎBHA8ꢆꢂꢐꢛꢂꢍꢂꢒꢕ ꢕꢀꢋꢂ ꢂꢇ ꢕꢕꢋꢂ&ꢂꢀꢔ ꢔꢌ ꢂ
ꢍꢌꢁ ꢄꢓ&ꢕ'ꢌ ꢂꢍ5?7H?5G98ꢆꢂꢐꢛꢂꢍꢂꢒꢕ ꢕꢔꢋꢂ ꢂꢇ ꢕꢇꢋꢂ&ꢂꢀꢔ ꢇꢇ ꢂ
ꢀ
ꢀꢓꢔꢓꢆꢂꢀꢓꢇꢁꢆꢂꢀꢌꢌꢌ ꢂ&%*ꢂFC97GEH@ꢂꢉꢍꢑꢍ?ꢌꢊꢆꢂδꢆꢂCC@ꢛꢂ
ꢄ ꢄꢔꢂFꢂꢉꢌ ꢆꢂ%9ꢊꢆꢂꢄ ꢇꢇꢂFꢂꢉꢌ ꢆꢂ%9ꢊꢆꢂꢄ ꢇꢅꢂ@ꢂꢉꢔ ꢆꢂꢍ ꢄꢆꢂ
C=C9E5M=A9ꢊꢆꢂꢌ ꢇꢔꢂFꢂꢉꢄ ꢆꢂꢍ ꢄ&ꢊꢆꢂꢇ ꢇꢌꢂ8ꢂꢉꢄ ꢆꢂꢍ ꢄꢆꢂJꢂꢙꢂ
ꢓ ꢒꢂ Mꢊꢆꢂꢇ ꢇꢒꢂGꢂꢉꢀ ꢆꢂ& ꢆꢂJꢂꢙꢂꢓ ꢌꢂ Mꢊꢆꢂꢒ ꢒꢄꢂFꢂꢉꢀ ꢆꢂ& ꢊꢆꢂ
ꢕ ꢌꢄꢂ8ꢂ5A8ꢂꢕ ꢔꢌꢂ8ꢂꢉꢇ ꢆꢂ Jꢂꢙꢂꢔ ꢄꢂ Mꢊꢆꢂꢕ ꢇꢄꢂ8ꢂ5A8ꢂꢕ ꢓꢕꢂ8ꢂ
ꢉꢇ ꢆꢂJꢂꢙꢂꢔ ꢄꢂ Mꢊꢆꢂꢒ ꢕꢌꢂ8 8ꢂꢉꢀ ꢆꢂJꢂꢙꢂꢔ ꢄꢆꢂꢄ ꢒꢂ Mꢊꢆꢂꢕ ꢁꢕꢂ8ꢂ
ꢉꢀ ꢆꢂJꢂꢙꢂꢔ ꢄꢂ Mꢊꢆꢂꢕ ꢀꢔꢂ8ꢂꢉꢀ ꢆꢂ Jꢂꢙꢂꢄ ꢒꢂ Mꢊꢆꢂꢕ ꢅꢀꢂFꢂꢉꢀ ꢆꢂ
& ꢍꢙ'ꢊ ꢂꢀꢌꢍꢂ&%*ꢂFC97GEH@ꢂꢉꢍꢑꢍ? ꢌꢊꢆꢂδꢍꢆꢂCC@ꢛꢂ
ꢀꢅ ꢕꢒꢆꢂꢇꢒ ꢄꢇꢆꢂꢇꢕ ꢔꢕꢆꢂꢓꢌ ꢄꢓꢆꢂꢓꢓ ꢌꢀꢆꢂꢒꢄ ꢕꢁꢆꢂꢀꢁꢔ ꢁꢔꢆꢂ
ꢀꢀꢔ ꢀꢓꢆꢂꢀꢄꢁ ꢌꢀꢆꢂꢀꢄꢄ ꢌꢀꢆꢂꢀꢄꢕ ꢒꢔꢆꢂꢀꢄꢕ ꢕꢕꢆꢂꢀꢌꢁ ꢀꢁꢆꢂ
ꢀꢌꢌ ꢓꢔꢆꢂꢀꢌꢇ ꢇꢁꢆꢂꢀꢌꢇ ꢔꢁꢆꢂꢀꢌꢒ ꢅꢕꢆꢂꢀꢇꢄ ꢔꢁꢆꢂꢀꢇꢒ ꢒꢕꢆꢂ
ꢀꢇꢅ ꢅꢀꢆꢂꢀꢒꢓ ꢓꢅ ꢂꢎBHA8ꢆꢂꢐꢛꢂꢍꢂꢒꢔ ꢌꢄꢋꢂ ꢂꢒ ꢓꢓꢋꢂ&ꢂꢀꢇ ꢒꢌ ꢂ
ꢍꢄꢕ ꢌꢀ&ꢓ'ꢌ ꢂꢍ5?7H?5G98ꢆꢂꢐꢛꢂꢍꢂꢒꢔ ꢇꢔꢋꢂ ꢂꢒ ꢒꢁꢋꢂ&ꢂꢀꢇ ꢕꢅ
(4-{4-Methyl-3-[4-(pyridin-3-yl)pyrimidin-2-yl-
amino]phenylaminomethyl}phenyl)(4-methylpiper-
azin-1-yl)methanone (23).ꢂ1=9?8ꢂꢒꢒꢐꢆꢂ?=;<Gꢂ;E5Lꢂ7ELFꢈ
G5?Fꢆꢂ@CꢂꢀꢁꢔPꢀꢀꢁRꢍꢂꢉ:EB@ꢂꢍ ꢍ? ꢌP<9K5A9ꢊ ꢂ!*ꢂFC97ꢈ
GEH@ꢂꢉ#ꢏEꢊꢆꢂ νꢆꢂ7@PꢀꢛꢂꢌꢇꢄꢁPꢌꢓꢁꢁꢆꢂꢀꢒꢔꢁꢆꢂꢀꢓꢇꢁꢆꢂꢀꢌꢅꢓ ꢂꢂ
4-[(Morpholin-4-yl)methyl]-N-{3-[4-(pyridin-
3-yl)pyrimidin-2-ylamino]phenyl}benzamide (30).ꢂ
1=9?8ꢂꢔꢇꢐꢆꢂL9??BJꢂ7ELFG5?Fꢆꢂ@CꢂꢀꢕꢕRꢍ ꢂ!*ꢂFC97GEH@ꢂ
ꢉ#ꢏEꢊꢆꢂνꢆꢂ7@Pꢀꢛꢂꢌꢌꢄꢁꢆꢂꢀꢅꢓꢓꢆꢂꢀꢒꢇꢅꢆꢂꢀꢔꢔꢕꢆꢂꢀꢓꢌꢕ ꢂꢀ ꢂ&%*ꢂ
FC97GEH@ꢂꢉꢍꢑꢍ?ꢌꢊꢆꢂδꢆꢂCC@ꢛꢂꢄ ꢇꢇꢂFꢂꢉꢇ ꢆꢂꢍ ꢄꢆꢂ@BEC<Bꢈ
?=A9ꢊꢆꢂꢌ ꢓꢇꢂFꢂꢉꢀ ꢊꢆꢂꢌ ꢕꢀꢂGꢂꢉꢇ ꢆꢂꢍ ꢄꢆꢂ@BEC<B?=A9ꢆꢂ Jꢂꢙꢂꢂ
ꢇ ꢄꢂ Mꢊꢆꢂꢕ ꢀꢕꢂ8ꢂꢉꢀ ꢆꢂ Jꢂꢙꢂꢓ ꢀꢂ Mꢊꢆꢂꢕ ꢄꢌꢂ8ꢂꢉꢀ ꢆꢂ Jꢂꢙꢂꢂ
ꢔ ꢁꢂ Mꢊꢆꢂꢕ ꢌꢄꢂGꢂꢉꢀ ꢆꢂ Jꢂꢙꢂꢔ ꢁꢂ Mꢊꢆꢂꢕ ꢇꢒPꢕ ꢇꢀꢂ@ꢂꢉꢇ ꢊꢆꢂ
ꢕ ꢒꢔꢂFꢂꢉꢀ ꢊꢆꢂꢕ ꢔꢓꢂ8ꢂꢉꢄ ꢊꢆꢂꢔ ꢀꢔꢂFꢂꢉꢀ ꢊꢆꢂꢔ ꢄꢅꢂFꢂꢉꢀ ꢊꢆꢂꢂ
ꢔ ꢇꢓꢂꢉꢀ ꢆꢂJꢂꢙꢂꢔ ꢁꢂ Mꢊꢆꢂꢔ ꢓꢄꢂ8ꢂꢉꢀ ꢆꢂ Jꢂꢙꢂꢓ ꢁꢂ Mꢊꢆꢂꢔ ꢕꢁꢂ8ꢂ
ꢉꢀ ꢆꢂJꢂꢙꢂꢇ ꢓꢂ Mꢊꢆꢂꢅ ꢄꢕꢂFꢂꢉꢀ ꢊ ꢂ ꢀꢌꢍꢂ&%*ꢂFC97GEH@ꢂ
ꢉꢍꢑꢍ?ꢌꢊꢆꢂδꢍꢆꢂCC@ꢛꢂꢓꢌ ꢓꢒꢆꢂꢒꢄ ꢔꢕꢆꢂꢒꢒ ꢅꢀꢂꢉꢍ@BEC<ꢊꢆꢂꢀꢁꢔ ꢌꢓꢆꢂ
ꢀꢀꢁ ꢅꢓꢆꢂꢀꢀꢇ ꢀꢒꢆꢂꢀꢀꢓ ꢄꢄꢆꢂꢀꢄꢌ ꢒꢅꢆꢂꢀꢄꢕ ꢀꢁꢆꢂꢀꢄꢅ ꢄꢅꢆꢂ
ꢀꢄꢅ ꢌꢔꢆꢂꢀꢌꢄ ꢒꢁꢆꢂꢀꢌꢌ ꢔꢕꢆꢂꢀꢌꢇ ꢕꢓꢆꢂꢀꢌꢔ ꢒꢒꢆꢂꢀꢇꢁ ꢀꢕꢆꢂ
ꢀꢇꢄ ꢁꢅꢆꢂꢀꢇꢔ ꢇꢕꢆꢂꢀꢓꢀ ꢇꢁꢆꢂꢀꢓꢔ ꢅꢀꢆꢂꢀꢒꢁ ꢀꢕꢆꢂꢀꢒꢄ ꢇꢅꢆꢂ
ꢀꢒꢓ ꢓꢇ ꢂꢎBHA8ꢆꢂꢐꢛꢂꢍꢂꢒꢅ ꢇꢁꢋꢂ ꢂꢓ ꢓꢒꢋꢂ&ꢂꢀꢕ ꢔꢕ ꢂ
ꢍꢄꢕ ꢄꢒ&ꢒ'ꢄ ꢂꢍ5?7H?5G98ꢆꢂꢐꢛꢂꢍꢂꢒꢅ ꢓꢀꢋꢂ ꢂꢓ ꢒꢄꢋꢂ&ꢂꢀꢔ ꢁꢀ ꢂ
ꢀ
ꢂ&%*ꢂFC97GEH@ꢂꢉꢑ%+'ꢈ dꢒꢊꢆꢂδꢆꢂCC@ꢛꢂꢄ ꢁꢒꢂFꢂꢉꢌ ꢆꢂ
ꢍ ꢌꢊꢆꢂꢄ ꢀꢒꢂFꢂꢉꢌ ꢆꢂꢍ ꢌꢊꢆꢂꢄ ꢇꢅꢂ6E Fꢂꢉꢇ ꢊꢂ5A8ꢂꢌ ꢌꢒꢂ6E Fꢂ
ꢉꢇ ꢊꢂꢉꢍ ꢄꢆꢂC=C9E5M=A9ꢊꢆꢂꢇ ꢄꢕꢂ8ꢂꢉꢄ ꢆꢂꢍ ꢄꢆꢂJꢂꢙꢂꢓ ꢅꢂ Mꢊꢆꢂ
ꢒ ꢀꢇꢂ@ꢂꢉꢀ ꢊꢆꢂꢒ ꢌꢌꢂ8ꢂꢉꢀ ꢊꢆꢂꢒ ꢔꢒꢂ@ꢂꢉꢄ ꢊꢆꢂꢕ ꢌꢌꢂ8ꢂꢉꢄ ꢆꢂJꢂꢙꢂ
ꢔ ꢀꢂ Mꢊꢆꢂꢕ ꢇꢁꢂ@ꢂꢉꢌ ꢊꢆꢂꢕ ꢓꢌꢂ@ꢂꢉꢀ ꢊꢆꢂꢔ ꢇꢄꢂ@ꢂꢉꢄ ꢊꢆꢂꢂ
ꢔ ꢒꢔꢂ8ꢂꢉꢄ ꢆꢂ Jꢂꢙꢂꢔ ꢀꢂ Mꢊꢆꢂꢅ ꢄꢓꢂFꢂꢉꢀ ꢊ ꢂ ꢀꢌꢍꢂ&%*ꢂFC97ꢈ
GEH@ꢂꢉꢑ%+'ꢈdꢒꢊꢆꢂδꢍꢆꢂCC@ꢛꢂꢀꢕ ꢀꢇꢆꢂꢇꢓ ꢓꢇꢆꢂꢇꢒ ꢇꢌꢆꢂꢀꢁꢕ ꢁꢅꢆꢂ
ꢀꢁꢔ ꢅꢄꢆꢂꢀꢁꢅ ꢇꢄꢆꢂꢀꢀꢅ ꢇꢄꢆꢂꢀꢄꢌ ꢕꢓꢆꢂꢀꢄꢒ ꢅꢄꢆꢂꢀꢄꢒ ꢅꢕꢆꢂ
ꢀꢌꢁ ꢌꢇꢆꢂꢀꢌꢄ ꢄꢀꢆꢂꢀꢌꢇ ꢁꢕꢆꢂꢀꢌꢇ ꢀꢔꢆꢂꢀꢌꢔ ꢁꢄꢆꢂꢀꢇꢄ ꢀꢓꢆꢂ
ꢀꢇꢒ ꢅꢄꢆꢂꢀꢇꢔ ꢁꢕꢆꢂꢀꢓꢀ ꢌꢁꢆꢂꢀꢓꢅ ꢌꢁꢆꢂꢀꢒꢀ ꢀꢇꢆꢂꢀꢒꢀ ꢌꢔꢆꢂ
ꢀꢒꢔ ꢔꢅ ꢂ%5FFꢂFC97GEH@ꢆꢂ mꢖzꢂ ꢉIE9?ꢆꢂꢐꢊꢛꢂꢇꢅꢌꢂꢉꢇꢁꢊꢂ3 M4ꢚꢆꢂ
ꢇꢌꢔꢂꢉꢇꢄꢊꢆꢂꢌꢅꢇꢂꢉꢇꢌꢊꢂ3 MꢂPꢂ& (ꢍ ꢄꢊꢇ&ꢍ ꢌ4ꢚꢆꢂꢌꢒꢓꢂꢉꢅꢔꢊꢆꢂ
ꢄꢕꢒꢂꢉꢒꢔꢊꢆꢂꢄꢒꢄꢂꢉꢄꢁꢊꢆꢂꢀꢀꢔꢂꢉꢇꢔꢊꢆꢂꢕꢁꢂꢉꢅꢔꢊꢆꢂꢓꢒꢂꢉꢇꢁꢊ ꢂꢎBHA8ꢆꢂ
ꢐꢛꢂꢍꢂꢕꢁ ꢇꢓꢋꢂ ꢂꢒ ꢄꢅꢋꢂ&ꢂꢀꢅ ꢒꢅ ꢂꢍ ꢌꢀ&ꢕ' ꢂꢍ5?7H?5G98ꢆꢂ
ꢄꢅ
ꢐꢛꢂꢍꢂꢕꢁ ꢓꢒꢋꢂ ꢂꢒ ꢌꢌꢋꢂ&ꢂꢀꢅ ꢔꢒ ꢂMꢂꢇꢅꢌ ꢒꢄ ꢂ
Reduction of nitro compounds 14 and 16 (gen-
eral procedure).ꢂ,<9ꢂE957G=BAꢂJ5Fꢂ75EE=98ꢂBHGꢂ577BE8ꢈ
=A;ꢂGBꢂG<9ꢂCEB798HE9ꢂ89F7E=698ꢂ=Aꢂ3ꢀꢓ4 ꢂ*5A9LꢂA=7>9?ꢆꢂ
ꢁ ꢓꢂ@@B?ꢆꢂ5A8ꢂ5ꢂFB?HG=BAꢂB:ꢂꢔꢁꢐꢂ5DH9BHFꢂ<L8E5M=A9ꢂ
<L8E5G9ꢂꢉꢄꢓꢂ@@B?ꢊꢂ=Aꢂꢓꢂ@$ꢂB:ꢂ@9G<5AB?ꢂJ9E9ꢂ58898ꢂGBꢂ
5ꢂFHFC9AF=BAꢂB:ꢂꢀ ꢄꢂ;ꢂꢉꢄ ꢓꢂ@@B?ꢊꢂB:ꢂ7B@CBHA8ꢂ 14ꢂBEꢂ
4-[(2-Methyl-5-nitrophenylamino)methyl]-N-
{4-[(4-methylpiperazin-1-yl)methyl]phenyl}benz-
amide (25).ꢂ1=9?8ꢂꢕꢕꢐꢆꢂL9??BJꢂ7ELFG5?Fꢆꢂ@CꢂꢀꢓꢓPꢂ
ꢀꢒꢁRꢍ ꢂ!*ꢂFC97GEH@ꢂꢉ#ꢏEꢊꢆꢂ νꢆꢂ7@PꢀꢛꢂꢌꢇꢌꢔPꢌꢇꢄꢔꢆꢂꢌꢄꢕꢅꢆꢂ
ꢀꢒꢓꢁꢆꢂꢀꢓꢔꢔꢆꢂꢀꢓꢇꢁ ꢂꢀ ꢂ&%*ꢂFC97GEH@ꢂꢉꢍꢑꢌ'ꢑꢊꢆꢂδꢆꢂ
*-++!ꢃ&ꢂꢂ"'-*&ꢃ$ꢂꢂ'ꢎꢂꢂ'*ꢗꢃ&!ꢍꢂꢂꢍ ꢘ%!+,*1ꢂꢂꢂ.B? ꢂꢂꢓꢀꢂꢂꢂ&B ꢂꢂꢀꢂꢂꢂꢄꢁꢀꢓꢂ

#'*'$ꢘ.ꢃꢂꢂ9Gꢂ5? ꢂ
ꢀꢁꢔꢂ
16ꢂ=Aꢂꢀꢓꢂ@$ꢂB:ꢂ@9G<5AB?ꢆꢂ5A8ꢂG<9ꢂ@=KGHE9ꢂJ5FꢂFG=EE98ꢂ ꢀꢌꢀ ꢅꢒꢆꢂꢀꢌꢄ ꢓꢕꢆꢂꢀꢌꢇ ꢄꢕꢆꢂꢀꢌꢒ ꢀꢓꢆꢂꢀꢌꢔ ꢄꢁꢆꢂꢀꢇꢇ ꢕꢅꢆꢂ
:BEꢂꢁ ꢓꢂ<ꢂ5GꢂEBB@ꢂG9@C9E5GHE9 ꢂ,<9ꢂ@=KGHE9ꢂ:B5@98ꢂ5A8ꢂ ꢀꢇꢒ ꢓꢇꢆꢂꢀꢇꢕ ꢄꢁꢆꢂꢀꢇꢕ ꢅꢅꢆꢂꢀꢓꢀ ꢌꢁꢆꢂꢀꢓꢅ ꢀꢕꢆꢂꢀꢓꢅ ꢅꢕꢆꢂ
J5E@98ꢂHCꢆꢂ5A8ꢂG<9ꢂ=A=G=5?ꢂ7B@CBHA8ꢂ;E58H5??Lꢂ8=Fꢈ
FB?I98 ꢂ,<9ꢂ@=KGHE9ꢂJ5FꢂG<9Aꢂ<95G98ꢂ:BEꢂꢄꢂ<ꢂ5GꢂꢒꢁRꢍꢂ
HA89EꢂFG=EE=A;ꢂ5A8ꢂ?9:GꢂBI9EA=;<GꢆꢂG<9ꢂ75G5?LFGꢂJ5Fꢂ
:=?G9E98ꢂB::ꢂG<EBH;<ꢂ5ꢂ:=?G9EꢂC5C9Eꢆꢂ5A8ꢂG<9ꢂ:=?GE5G9ꢂJ5Fꢂ
9I5CBE5G98 ꢂ,<9ꢂE9F=8H9ꢂJ5Fꢂ 8=FFB?I98ꢂ=Aꢂ9G<L?ꢂ579G5G9ꢂ
5GꢂꢓꢓPꢒꢁRꢍꢆꢂꢌꢂ;ꢂB:ꢂ7<5E7B5?ꢂJ5Fꢂ58898ꢆꢂG<9ꢂ@=KGHE9ꢂ
J5Fꢂ<95G98ꢂ:BEꢂꢁ ꢓꢂ<ꢂHA89EꢂE9:?HKꢂ5A8ꢂ:=?G9E98ꢂG<EBH;<ꢂ
79?=G9ꢆꢂ5A8ꢂG<9ꢂFBE69AGꢂJ5FꢂJ5F<98ꢂJ=G<ꢂ9G<L?ꢂ579G5G9 ꢂ
,<9ꢂ:=?GE5G9ꢂJ5Fꢂ7B@6=A98ꢂJ=G<ꢂG<9ꢂJ5F<=A;FꢆꢂJ5F<98ꢂ
J=G<ꢂJ5G9Eꢆꢂ8E=98ꢂBI9EꢂFB8=H@ꢂFH?:5G9ꢆꢂ5A8ꢂ9I5CBE5G98ꢂ
GBꢂꢀꢖꢌꢂB:ꢂG<9ꢂ=A=G=5?ꢂIB?H@9ꢆꢂ5A8ꢂG<9ꢂCEB8H7Gꢆꢂ7B@CBHA8ꢂ
15ꢂBEꢂ17ꢆꢂJ5FꢂCE97=C=G5G98ꢂJ=G<ꢂC9GEB?9H@ꢂ9G<9E ꢂꢂ
ꢀꢒꢀ ꢄꢅꢆꢂꢀꢒꢇ ꢅꢁ ꢂꢎBHA8ꢆꢂꢐꢛꢂꢍꢂꢕꢄ ꢀꢔꢋꢂ ꢂꢓ ꢒꢁꢋꢂ&ꢂꢀꢔ ꢅꢇ ꢂ
ꢍꢌꢀ ꢄꢅ&ꢕ' ꢂꢍ5?7H?5G98ꢆꢂꢐꢛꢂꢍꢂꢕꢄ ꢄꢀꢋꢂ ꢂꢓ ꢒꢕꢋꢂ&ꢂꢀꢅ ꢁꢄ ꢂ
4-[(4-Methylpiperazin-1-yl)methyl]aniline (24)ꢂ
J5FꢂFLAG<9F=M98ꢂ6LꢂE98H7G=I9ꢂ5?>L?5G=BAꢂB:ꢂꢀꢈ@9G<L?ꢈ
C=C9E5M=A9ꢂJ=G<ꢂpꢈA=GEB69AM5?89<L89ꢂ5A8ꢂFH6F9DH9AGꢂ
E98H7G=BAꢂB:ꢂꢀꢈ@9G<L?ꢈꢇꢈꢉꢇꢈA=GEB69AML?ꢊC=C9E5M=A9ꢂ57ꢈ
7BE8=A;ꢂGBꢂ3ꢒꢆꢂꢀꢁ4 ꢂ1=9?8ꢂꢌꢁꢐꢆꢂB=?Lꢂ?=DH=8 ꢂ!*ꢂFC97GEH@ꢂ
ꢉ:=?@ꢊꢆꢂ νꢆꢂ7@Pꢀꢛꢂꢌꢇꢇꢓꢆꢂꢌꢌꢀꢁꢆꢂꢌꢀꢒꢀꢆꢂꢄꢅꢌꢒꢆꢂꢄꢔꢁꢇꢆꢂꢄꢕꢒꢄꢆꢂ
ꢀ
ꢀꢒꢇꢁꢆꢂꢀꢒꢀꢄꢆꢂꢀꢇꢓꢕ ꢂ ꢂ&%*ꢂFC97GEH@ꢂꢉꢑ%+'ꢈ dꢒꢊꢆꢂδꢆꢂ
CC@ꢛꢂꢄ ꢌꢒꢂFꢂꢉꢌ ꢆꢂꢍ ꢌꢊꢆꢂꢄ ꢓꢓꢂ@ꢂꢉꢔ ꢆꢂꢍ ꢄꢊꢆꢂꢌ ꢇꢓꢂFꢂꢉꢄ ꢆꢂ
ꢍ ꢄꢊꢆꢂꢒ ꢒꢇꢂ8ꢂꢉꢄ ꢆꢂJꢂꢙꢂꢔ ꢁꢂ Mꢊꢆꢂꢕ ꢁꢔꢂ8ꢂꢉꢄ ꢆꢂJꢂꢙꢂꢔ ꢁꢂ Mꢊ ꢂ
%5FFꢂFC97GEH@ꢆꢂmꢖzꢂꢉIE9?ꢆꢂꢐꢊꢛꢂꢄꢁꢓꢂꢉꢄꢓꢊꢂ3 M4ꢚꢆꢂꢀꢁꢒꢂꢉꢀꢁꢁꢊꢂ
3Mꢂ‒ꢂ&ꢉꢍ ꢄꢊꢇ&%94ꢚꢆꢂꢅꢅꢂ3&ꢉꢍ ꢄꢊꢇ&%94ꢚꢂꢉꢓꢁꢊ ꢂꢎBHA8ꢆꢂ
ꢐꢛꢂꢍꢂꢕꢁ ꢌꢓꢋꢂ ꢂꢅ ꢄꢒꢋꢂ&ꢂꢄꢁ ꢒꢓ ꢂꢍꢀꢄ ꢀꢅ&ꢌ ꢂꢍ5?7H?5G98ꢆꢂꢐꢛꢂ
ꢍꢂꢕꢁ ꢄꢁꢋꢂ ꢂꢅ ꢌꢌꢋꢂ&ꢂꢄꢁ ꢇꢕ ꢂMꢂꢄꢁꢓ ꢌꢀ ꢂꢂ
4-[(3-Amino-4-methylphenyl)aminomethyl]-
N-{3-[4-(pyridin-3-yl)pyrimidin-2-ylamino]phenyl}-
benzamide (15).ꢂ1=9?8ꢂꢕꢕꢐꢆꢂL9??BJP6EBJAꢂ7ELFG5?Fꢆꢂ
@CꢂꢀꢀꢅPꢀꢄꢀRꢍ ꢂ!*ꢂFC97GEH@ꢂꢉ#ꢏEꢊꢆꢂ νꢆꢂ7@Pꢀꢛꢂꢌꢌꢕꢔꢆꢂ
Amides 27, 28, and 31 (general procedure).ꢂꢃꢂ@=Kꢈ
GHE9ꢂB:ꢂꢀꢁꢂ@@B?ꢂB:ꢂ57=8ꢂ 29ꢂ<L8EB7<?BE=89ꢆꢂꢕꢂ@$ꢂB:ꢂ
CLE=8=A9ꢆꢂ5A8ꢂꢕꢂ@$ꢂB:ꢂ7<?BEB:BE@ꢂJ5Fꢂ7BB?98ꢂGBꢂꢁRꢍꢆꢂ
ꢁRꢍꢆꢂꢁ ꢕꢇꢂ@$ꢂꢉꢀꢀꢂ@@B?ꢊꢂB:ꢂG<=BAL?ꢂ7<?BE=89ꢂJ5Fꢂ
58898ꢆꢂ5A8ꢂG<9ꢂ@=KGHE9ꢂJ5FꢂFG=EE98ꢂ:BEꢂꢁ ꢓꢂ<ꢂBAꢂ7BB?=A;ꢂ
5A8ꢂ?9:GꢂBI9EA=;<G ꢂ'AꢂG<9ꢂA9KGꢂ85Lꢆꢂꢀꢁꢂ@$ꢂB:ꢂCLE=8=A9ꢂ
5A8ꢂꢀꢁꢂ@$ꢂB:ꢂ7<?BEB:BE@ꢂJ9E9ꢂ58898ꢆꢂG<9ꢂ@=KGHE9ꢂJ5Fꢂ
FG=EE98ꢂ:BEꢂꢀꢂ<ꢂ5GꢂEBB@ꢂG9@C9E5GHE9ꢆꢂꢕPꢔꢂ@@B?ꢂB:ꢂ
5@=A9ꢂ3ꢆꢂ6ꢆꢂBEꢂ24ꢂJ5Fꢂ58898ꢆꢂ5A8ꢂG<9ꢂ@=KGHE9ꢂJ5Fꢂ
FG=EE98ꢂ:BEꢂꢒPꢀꢄꢂ<ꢂꢉ,$ꢍꢊ ꢂ/<9AꢂG<9ꢂE957G=BAꢂJ5Fꢂ7B@ꢈ
C?9G9ꢆꢂG<9ꢂ@=KGHE9ꢂJ5Fꢂ9I5CBE5G98ꢆꢂG<9ꢂE9F=8H9ꢂJ5Fꢂ
GE95G98ꢂJ=G<ꢂ5DH9BHFꢂ5@@BA=5ꢆꢂ5A8ꢂG<9ꢂCE97=C=G5G9ꢂJ5Fꢂ
:=?G9E98ꢂB::ꢆꢂJ5F<98ꢂJ=G<ꢂ75??98ꢂJ5G9Eꢆꢂ5A8ꢂE97ELFG5?ꢈ
ꢀ
ꢌꢄꢓꢒꢆꢂꢌꢁꢒꢌꢆꢂꢀꢒꢒꢀꢆꢂꢀꢒꢀꢇꢆꢂꢀꢓꢓꢔ ꢂ ꢂ&%*ꢂFC97GEH@ꢂ
ꢉꢑ%+'ꢈdꢒꢊꢆꢂδꢆꢂCC@ꢛꢂꢀ ꢅꢁꢂFꢂꢉꢌ ꢆꢂ%9ꢊꢆꢂꢇ ꢄꢔꢂFꢂꢉꢄ ꢆꢂ
ꢍ ꢄꢊꢆꢂꢇ ꢁꢁꢂ6E Fꢂꢉꢄ ꢆꢂ& ꢄꢊꢆꢂꢓ ꢔꢒꢂ8 8ꢂꢉꢀ ꢆꢂJ ꢂꢙꢂꢔ ꢁꢆꢂꢂ
ꢀ ꢅꢂ Mꢊꢆꢂꢓ ꢅꢂFꢂꢉꢀ ꢊꢆꢂꢒ ꢒꢀꢂ8ꢂꢉꢀ ꢆꢂ Jꢂꢙꢂꢔ ꢀꢂ Mꢊꢆꢂꢕ ꢄꢔꢂ@ꢂ
ꢉꢄ ꢊꢆꢂꢕ ꢇꢕꢂ8ꢂꢉꢄ ꢆꢂJꢂꢙꢂꢔ ꢁꢂ Mꢊꢆꢂꢕ ꢓꢄꢂ8ꢂꢉꢀ ꢆꢂJꢂꢙꢂꢓ ꢄꢂ Mꢊꢆꢂ
ꢕ ꢓꢒꢂ8 8ꢂꢉꢀ ꢆꢂJꢂꢙꢂꢔ ꢁꢆꢂꢓ ꢄꢂ Mꢊꢆꢂꢕ ꢅꢀꢂ8ꢂꢉꢀ ꢆꢂJꢂꢙꢂꢔ ꢄꢂ Mꢊꢆꢂ
ꢔ ꢇꢇꢂFꢂꢉꢀ ꢊꢆꢂꢔ ꢒꢁꢂ8ꢂꢉꢀ ꢆꢂ Jꢂꢙꢂꢓ ꢀꢂ Mꢊꢆꢂꢔ ꢒꢌꢂ8ꢂꢉꢀ ꢆꢂ Jꢂꢙꢂ
ꢔ ꢀꢂ Mꢊꢆꢂꢔ ꢕꢄꢂ8 8ꢂꢉꢀ ꢆꢂ Jꢂꢙꢂꢇ ꢒꢆꢂꢀ ꢄꢂ Mꢊꢆꢂꢅ ꢕꢅꢂFꢂꢉꢀ ꢊꢆꢂ
ꢀꢁ ꢀꢅꢂFꢂꢉꢀ ꢊ ꢂ ꢀꢌꢍꢂ&%*ꢂFC97GEH@ꢂꢉꢑ%+'ꢈ dꢒꢊꢆꢂδꢍꢆꢂ
CC@ꢛꢂꢀꢒ ꢁꢓꢆꢂꢇꢒ ꢁꢇꢆꢂꢀꢁꢄ ꢌꢁꢆꢂꢀꢁꢕ ꢕꢄꢆꢂꢀꢀꢀ ꢄꢅꢆꢂꢀꢀꢌ ꢔꢇꢆꢂ
ꢀꢀꢇ ꢇꢇꢆꢂꢀꢄꢌ ꢇꢒꢆꢂꢀꢄꢒ ꢇꢒꢆꢂꢀꢄꢕ ꢄꢄꢆꢂꢀꢄꢕ ꢅꢔꢆꢂꢀꢄꢅ ꢔꢔꢆꢂ
ꢀꢌꢀ ꢕꢒꢆꢂꢀꢌꢄ ꢅꢄꢆꢂꢀꢌꢇ ꢄꢒꢆꢂꢀꢌꢔ ꢅꢓꢆꢂꢀꢇꢁ ꢀꢒꢆꢂꢀꢇꢇ ꢇꢄꢆꢂ
ꢀꢇꢒ ꢅꢒꢆꢂꢀꢇꢕ ꢔꢕꢆꢂꢀꢓꢀ ꢁꢔꢆꢂꢀꢓꢇ ꢇꢒꢆꢂꢀꢓꢔ ꢅꢕꢆꢂꢀꢓꢅ ꢔꢀꢆꢂ
ꢀꢒꢀ ꢀꢒꢆꢂꢀꢒꢇ ꢅꢕꢆꢂꢀꢒꢅ ꢅꢅꢆꢂꢀꢕꢀ ꢁꢌ ꢂꢎBHA8ꢆꢂꢐꢛꢂꢍꢂꢕꢀ ꢔꢁꢋꢂ
ꢂꢓ ꢌꢒꢋꢂ&ꢂꢀꢅ ꢌꢅ ꢂꢍ ꢌꢁ ꢄꢕ&ꢕ' ꢂꢍ5?7H?5G98ꢆꢂꢐꢛꢂꢍꢂꢕꢀ ꢔꢇꢋꢂ
ꢂꢓ ꢇꢌꢋꢂ&ꢂꢀꢅ ꢓꢓ
?=M98ꢂ:EB@ꢂ7<?BEB:BE@P8=9G<L?ꢂ9G<9Eꢂꢉꢀꢛꢀꢊ ꢂ
ꢂ
ꢂ
N-(4-Methyl-3-nitrophenyl)-4-(morpholin-4-yl-
methyl)benzamide (27).ꢂ1=9?8ꢂꢅꢓꢐꢆꢂL9??BJꢂ7ELFG5?Fꢆꢂ
@CꢂꢀꢌꢔRꢍ ꢂ!*ꢂFC97GEH@ꢂꢉ#ꢏEꢊꢆꢂ νꢆꢂ7@Pꢀꢛꢂꢌꢌꢄꢅꢆꢂꢄꢅꢄꢌꢆꢂ
4-[(3-Amino-4-methylphenylamino)methyl]-N-
{2-methyl-5-[4-(pyridin-3-yl)pyrimidin-2-ylamino]-
phenyl}benzamide (17).ꢂ1=9?8ꢂꢒꢌꢐꢆꢂL9??BJꢂ7ELFG5?Fꢆꢂ
@CꢂꢀꢌꢓPꢀꢌꢔRꢍ ꢂ!*ꢂFC97GEH@ꢂꢉ#ꢏEꢊꢆꢂ νꢂ7@Pꢀꢛꢂꢌꢇꢄꢓꢆꢂ
ꢄꢅꢀꢅꢆꢂꢀꢒꢕꢓꢆꢂꢀꢓꢄꢕꢆꢂꢀꢇꢄꢄ ꢂꢀ ꢂ&%*ꢂFC97GEH@ꢂꢂ
ꢉꢑ%+'ꢈdꢒꢊꢆꢂδꢆꢂCC@ꢛꢂꢀ ꢔꢅꢂꢉꢌ ꢆꢂ%9ꢊꢆꢂꢄ ꢀꢔꢂꢉꢌ ꢆꢂ%9ꢊꢆꢂ
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