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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
Notes
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Reaction equation

HRID 1642561 reaction equation
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]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 3

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
125 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-51d0047f21e84cad86114faa5a24de12
Source dataset
uspto-grants-2012_02
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08119655B2

Reaction notes

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