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Cesium carbonate → 5-(3-(ethylsulfonyl)phenyl)-3-methyl-8-((1-methylpiperidin-4-yl)methoxy)-9H-pyrido[2,3-b]indole

HRID 1642561
ノート
印刷プレビュー

反応式

HRID 1642561 の反応式
Cl[C:2]1[CH:10]=[CH:9][C:8]([O:11][CH2:12][CH:13]2[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]2)=[C:7]2[C:3]=1[C:4]1[CH:23]=[C:22]([CH3:24])[CH:21]=[N:20][C:5]=1[NH:6]2.[CH2:25]([S:27]([C:30]1[CH:31]=[C:32](B(O)O)[CH:33]=[CH:34][CH:35]=1)(=[O:29])=[O:28])[CH3:26].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.C([O-])([O-])=O.[Cs+].[Cs+]>CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].O1CCOCC1>[CH2:25]([S:27]([C:30]1[CH:35]=[C:34]([C:2]2[CH:10]=[CH:9][C:8]([O:11][CH2:12][CH:13]3[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]3)=[C:7]3[C:3]=2[C:4]2[CH:23]=[C:22]([CH3:24])[CH:21]=[N:20][C:5]=2[NH:6]3)[CH:33]=[CH:32][CH:31]=1)(=[O:28])=[O:29])[CH3:26]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

8

反応物 4

HCID 10796Cesium carbonateHCID 75806TricyclohexylphosphineHCID 164271023-Ethylsulfonylphenylboronic acidHCID 588801545-chloro-3-methyl-8-((1-methylpiperidin-4-yl)methoxy)-9H-pyrido[2,3-b]indole

生成物 1

HCID 588800825-(3-(ethylsulfonyl)phenyl)-3-methyl-8-((1-methylpiperidin-4-yl)methoxy)-9H-pyrido[2,3-b]indole収率 75.2%

試薬・触媒・溶媒 3

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladium触媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
125 °C

実験手順

To a stirred solution of Compound 175 (170 mg, 0.49 mmol) and 3-(ethylsulfonyl)phenylboronic acid (265 mg, 1.24 mmol) in anhydrous and degassed dioxane (5 mL), were added Pd(dba)2 (70 mg, 0.12 mmol), PCy3 (0.34 mL, 20% wt solution in toluene, 0.24 mmol) and Cs2CO3 (479 mg, 1.47 mmol), under nitrogen. After being stirred for 6 h. under reflux (oil bath temperature 125° C.) the reaction was diluted with EtOAc and filtered through a small pad of celite. The residue was washed thoroughly with EtOAc and 10% MeOH in CH2Cl2. All the washings and filtrate were concentrated in vacuum and the crude residue was triturated with ether and then with MeOH and then purified through preparative HPLC to give Compound 176 (176 mg, 75%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.20 (t, J=7.34 Hz, 3 H) 1.50-1.61 (m, 2 H) 2.18 (br. s., 1 H) 2.13-2.20 (m, 1 H) 2.23-2.31 (m, 5 H) 2.82 (s, 3 H) 2.98-3.09 (m, 2 H) 3.39 (q, J=7.34 Hz, 2 H) 3.54 (d, J=10.60 Hz, 2 H) 4.12 (d, J=6.52 Hz, 2 H) 7.06-7.17 (m, 2 H) 7.53 (s, 1 H) 7.85 (t, J=7.74 Hz, 1 H) 7.96 (d, J=7.66 Hz, 1 H) 8.00 (d, J=7.66 Hz, 1 H) 8.06 (s, 1 H) 8.28 (d, J=1.47 Hz, 1 H) 11.83 (br. s., 1 H), [M+H] calc'd for C27H32N3O3S, 478.2; found, 478.4; [M+H+TFA] calc'd for C29H33N3O5F3S, 592.2; found, 592.4.

後処理

  1. filtrationfiltered through a small pad of celite
  2. washThe residue was washed thoroughly with EtOAc and 10% MeOH in CH2Cl2
  3. concentrationAll the washings and filtrate were concentrated in vacuum
  4. customthe crude residue was triturated with ether
  5. customwith MeOH and then purified through preparative HPLC

出典と根拠

ORDレコード
ord-51d0047f21e84cad86114faa5a24de12
出典データセット
uspto-grants-2012_02
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08119655B2

反応ノート

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