Chinese Journal of Organic Chemistry ›› 2021, Vol. 41 ›› Issue (4): 1712-1721.DOI: 10.6023/cjoc202007059 Previous Articles Next Articles
ARTICLES
徐晨淏a,b,c,d, 龚云鹏a,b,c,d, 陈雅欣a,b,c,d, 宋启梦a,b,c,d, 李娇a,b,c,d, 郑一超a,b,c,d, 李雯a,b,c,d,*(), 孙凯a,b,c,d,*(), 刘宏民a,b,c,d,*()
收稿日期:
2020-07-26
修回日期:
2020-10-21
发布日期:
2020-12-05
通讯作者:
李雯, 孙凯, 刘宏民
基金资助:
Chenhao Xua,b,c,d, Yunpeng Gonga,b,c,d, Yaxin Chena,b,c,d, Qimeng Songa,b,c,d, Jiao Lia,b,c,d, Yichao Zhenga,b,c,d, Wen Lia,b,c,d,*(), Kai Suna,b,c,d,*(), Hongmin Liua,b,c,d,*()
Received:
2020-07-26
Revised:
2020-10-21
Published:
2020-12-05
Contact:
Wen Li, Kai Sun, Hongmin Liu
About author:
Supported by:
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Chenhao Xu, Yunpeng Gong, Yaxin Chen, Qimeng Song, Jiao Li, Yichao Zheng, Wen Li, Kai Sun, Hongmin Liu. Design, Synthesis and Activity Evaluation of Novel Bromodomain-Containing Protein 4 (BRD4) Small Molecule Inhibitor Based on ABBV-075[J]. Chinese Journal of Organic Chemistry, 2021, 41(4): 1712-1721.
Entry | Catalyst | Ligand | Base | Solvent | T/℃ | Time/h | Yielda/% |
---|---|---|---|---|---|---|---|
1 | Pd2(dba)3 | X-Phos | Cs2CO3 | 1,4-Dioxane/H2O (V∶V=4∶1) | 90 | 6 | 0 |
2 | Pd2(dba)3 | X-Phos | Cs2CO3 | DMSO | 90 | 6 | 0 |
3 | Pd2(dba)3 | X-Phos | Cs2CO3 | DMF | 90 | 6 | 0 |
4 | Pd2(dba)3 | X-Phos | K3PO4 | 1,4-Dioxane/H2O (V∶V=4∶1) | 90 | 6 | 0 |
5 | Pd2(dba)3 | X-Phos | Na2CO3 | 1,4-Dioxane/H2O (V∶V=4∶1) | 90 | 6 | 0 |
6 | Pd2(dba)3 | PPh3 | Cs2CO3 | 1,4-Dioxane/H2O (V∶V=4∶1) | 90 | 6 | 0 |
7 | Pd(OAc)2 | X-Phos | Cs2CO3 | 1,4-Dioxane/H2O (V∶V=4∶1) | 90 | 6 | 0 |
8 | Pd(OAc)2 | PPh3 | Cs2CO3 | 1,4-Dioxane/H2O (V∶V=4∶1) | 90 | 6 | 0 |
9 | Pd(dppf)Cl2 | None | Cs2CO3 | 1,4-Dioxane/H2O (V∶V=4∶1) | 90 | 6 | 0 |
10 | (dtbpf)PdCl2 | None | Cs2CO3 | 1,4-Dioxane/H2O (V∶V=4∶1) | 90 | 6 | 30 |
11 | (dtbpf)PdCl2 | None | K3PO4 | 1,4-Dioxane/H2O (V∶V=4∶1) | 90 | 6 | 12 |
12 | (dtbpf)PdCl2 | None | Na2CO3 | 1,4-Dioxane/H2O (V∶V=4∶1) | 90 | 6 | 10 |
13 | (dtbpf)PdCl2 | None | Cs2CO3 | 1,4-Dioxane/H2O (V∶V=4∶1) | 90 | 12 | 40 |
14 | (dtbpf)PdCl2 | None | Cs2CO3 | 1,4-Dioxane/H2O (V∶V=4∶1) | 90 | 24 | 40 |
15 | (dtbpf)PdCl2 | None | Cs2CO3 | 1,4-Dioxane | 90 | 12 | 0 |
16 | (dtbpf)PdCl2 | None | Cs2CO3 | DMSO | 90 | 12 | 0 |
17 | (dtbpf)PdCl2 | None | Cs2CO3 | 1,4-Dioxane/H2O (V∶V=4∶1) | 30 | 12 | 0 |
18 | (dtbpf)PdCl2 | None | Cs2CO3 | 1,4-Dioxane/H2O (V∶V=4∶1) | 60 | 12 | 0 |
Entry | Catalyst | Ligand | Base | Solvent | T/℃ | Time/h | Yielda/% |
---|---|---|---|---|---|---|---|
1 | Pd2(dba)3 | X-Phos | Cs2CO3 | 1,4-Dioxane/H2O (V∶V=4∶1) | 90 | 6 | 0 |
2 | Pd2(dba)3 | X-Phos | Cs2CO3 | DMSO | 90 | 6 | 0 |
3 | Pd2(dba)3 | X-Phos | Cs2CO3 | DMF | 90 | 6 | 0 |
4 | Pd2(dba)3 | X-Phos | K3PO4 | 1,4-Dioxane/H2O (V∶V=4∶1) | 90 | 6 | 0 |
5 | Pd2(dba)3 | X-Phos | Na2CO3 | 1,4-Dioxane/H2O (V∶V=4∶1) | 90 | 6 | 0 |
6 | Pd2(dba)3 | PPh3 | Cs2CO3 | 1,4-Dioxane/H2O (V∶V=4∶1) | 90 | 6 | 0 |
7 | Pd(OAc)2 | X-Phos | Cs2CO3 | 1,4-Dioxane/H2O (V∶V=4∶1) | 90 | 6 | 0 |
8 | Pd(OAc)2 | PPh3 | Cs2CO3 | 1,4-Dioxane/H2O (V∶V=4∶1) | 90 | 6 | 0 |
9 | Pd(dppf)Cl2 | None | Cs2CO3 | 1,4-Dioxane/H2O (V∶V=4∶1) | 90 | 6 | 0 |
10 | (dtbpf)PdCl2 | None | Cs2CO3 | 1,4-Dioxane/H2O (V∶V=4∶1) | 90 | 6 | 30 |
11 | (dtbpf)PdCl2 | None | K3PO4 | 1,4-Dioxane/H2O (V∶V=4∶1) | 90 | 6 | 12 |
12 | (dtbpf)PdCl2 | None | Na2CO3 | 1,4-Dioxane/H2O (V∶V=4∶1) | 90 | 6 | 10 |
13 | (dtbpf)PdCl2 | None | Cs2CO3 | 1,4-Dioxane/H2O (V∶V=4∶1) | 90 | 12 | 40 |
14 | (dtbpf)PdCl2 | None | Cs2CO3 | 1,4-Dioxane/H2O (V∶V=4∶1) | 90 | 24 | 40 |
15 | (dtbpf)PdCl2 | None | Cs2CO3 | 1,4-Dioxane | 90 | 12 | 0 |
16 | (dtbpf)PdCl2 | None | Cs2CO3 | DMSO | 90 | 12 | 0 |
17 | (dtbpf)PdCl2 | None | Cs2CO3 | 1,4-Dioxane/H2O (V∶V=4∶1) | 30 | 12 | 0 |
18 | (dtbpf)PdCl2 | None | Cs2CO3 | 1,4-Dioxane/H2O (V∶V=4∶1) | 60 | 12 | 0 |
Compd. | R1 | Inhibition/% at 10 μmol/L | IC50a/(μmol?L–1) |
---|---|---|---|
15a | H | 23 | — |
15b | 2,4-F2 | 5 | — |
15c | 3-CH3 | 20 | — |
15d | 4-CH3 | 3 | — |
15e | 3-OCH3 | 5 | – |
15f | 4-F | 20 | – |
(+)-JQ1 | 0.070±0.001 |
Compd. | R1 | Inhibition/% at 10 μmol/L | IC50a/(μmol?L–1) |
---|---|---|---|
15a | H | 23 | — |
15b | 2,4-F2 | 5 | — |
15c | 3-CH3 | 20 | — |
15d | 4-CH3 | 3 | — |
15e | 3-OCH3 | 5 | – |
15f | 4-F | 20 | – |
(+)-JQ1 | 0.070±0.001 |
Compd. | R1 | R2 | Inhibition/% at 10 μmol/L | IC50a/ (μmol?L–1) | Compd. | R1 | R2 | Inhibition/% at 10 μmol/L | IC50a/ (μmol?L–1) |
---|---|---|---|---|---|---|---|---|---|
15g | H | | 12 | – | 15m | H | | 5 | — |
15h | 3-F | | 13 | – | 15n | 2,4-F2 | | 35 | — |
15i | 4-F | | 25 | — | 15o | 2,4-F2 | | 51 | 16.39±1.20 |
15j | 4-CN | | 5 | — | 15p | 2,4-F2 | | 24 | — |
15k | H | | 28 | — | (+)-JQ1 | 0.070±0.001 | |||
15l | H | | 31 | — |
Compd. | R1 | R2 | Inhibition/% at 10 μmol/L | IC50a/ (μmol?L–1) | Compd. | R1 | R2 | Inhibition/% at 10 μmol/L | IC50a/ (μmol?L–1) |
---|---|---|---|---|---|---|---|---|---|
15g | H | | 12 | – | 15m | H | | 5 | — |
15h | 3-F | | 13 | – | 15n | 2,4-F2 | | 35 | — |
15i | 4-F | | 25 | — | 15o | 2,4-F2 | | 51 | 16.39±1.20 |
15j | 4-CN | | 5 | — | 15p | 2,4-F2 | | 24 | — |
15k | H | | 28 | — | (+)-JQ1 | 0.070±0.001 | |||
15l | H | | 31 | — |
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