Abstract
A convenient route for the synthesis of Novartis's second-generation anaplastic lymphoma kinase inhibitor Ceritinib (LDK378) involving starting materials that are commercially available has been achieved. The procedure employed mild reaction conditions and avoided the use of expensive reagents compared to the original synthetic route reported by Novartis. More importantly, gram scale synthesis was accomplished and this protocol could be valid in drug discovery synthesis.
References
1.
Kwak
E. L.
,
Bang
Y.-J.
, and
Camidge
D. R.
, N. Engl. J. Med. , 2010 , 363 , 1693 .
2.
Camidge
D.R.
,
Bang
Y. J.
, and
Iafrate
A. J.
, Lancet Oncol. , 2012 , 10 , 1011 .
3.
Shaw
A. T.
,
Kim
D.-W
, and
Jänne
P. A.
, N. Engl. J. Med. , 2013 , 368 , 2385 .
4.
Choi
Y. L.
,
Soda
M.
, and
Yamashita
Y.
, N. Engl. J. Med. , 2010 , 363 , 1734 .
5.
Katayamaa
R.
,
Khana
T. M.
, and
Benesa
C.
, Proc. Natl. Acad. Sci. USA , 2011 , 108 , 7535 .
6.
Kim
S.
,
Kim
T. M.
, and
Kim
D. W.
, J. Thorac. Oncol. , 2013 , 8 , 415 .
7.
Sang
J.
,
Acquaviva
J.
, and
Friedland
J. C.
, Cancer Discov. , 2013 , 3 , 430 .
8.
Doebele
R. C.
,
Pilling
A. B.
, and
Aisner
D. L.
, Clin. Cancer. Res. , 2012 , 18 , 1472 .
9.
Marsilje
T.H.
,
Pei
W.
,
Chen
B.
,
Lu
W.
,
Uno
T.
,
Jin
Y.
,
Jiang
T.
J. Med. Chem. , 2013 , 56 , 5675 .
10.
Chen
Z.
,
Akbay
E.
, and
Mikse
O.
, Clin. Cancer Res. , 2014 , 20 , 1204 .
11.
Perez
C.A.
,
Velez
M.
, and
Raez
L. E.
, Lung Cancer , 2014 , 84 , 110 .
12.
Park
K.
,
Heo
D. S.
, and
Cho
B. J.
, Clin. Oncol. , 2010 , 28 , 7596 .
13.
Kim
D.W.
, and
Mehra
R.
, J. Clin. Oncol. , 2014 , 32 , 8003 .
14.
Camidge
D.R.
,
Bang
Y. J.
, and
Kwak
E. L.
, Lancet Oncol. , 2012 , 13 , 1011 .
15.
Sundar
R.
,
Soong
R.
, and
Cho
B. C.
, Lung Cancer , 2014 , 85 , 101 .
16.
Hodgson
H. H.
, Chem. Rev. , 1947 , 40 , 251 .
17.
Mo
F.
,
Jiang
Y.
,
Qiu
D.
, and
Wang
J.
, Angew. Chem. , 2010 , 122 , 1890 .
18.
Qiu
D.
,
Jin
L.
,
Zheng
Z.
, and
Meng
H.
, J. Org. Chem. , 2013 , 78 , 1923 .
19.
Zhu
C.
, and
Yamane
M.
, Org. Lett. , 2012 , 14 , 4560
20.
Qiu
D.
,
Meng
H.
,
Jin
L.
,
Wang
S.
, and
Wang
J.-b.
, Angew. Chem. Int. Ed. , 2013 , 52 , 11581 .
21.
Rajeshkumar
V.
,
Chandrasekar
S.
, and
Sekar
G.
, Org. Biomol. Chem. , 2014 , 12 , 8512 .
22.
He
L.-M.
,
Qiu
G.
,
Gao
Y.-q.
, and
Wu
J.
, Org. Biomol. Chem. , 2014 , 12 , 6965 .
23.
Browne
D. L.
, Angew. Chem. Int. Ed. , 2014 , 53 , 1482 .
24.
Burnett
J. F.
, and
Zahler
R. E.
, Chem. Rev. , 1951 , 49 , 273 .