Triphenylphosphine → 3-chloro-6-(4-(2-(4-methylpiperazin-1-yl)ethoxy)phenyl)-9-(benzenesulfonyl)-9H-pyrido[2,3-b]indole

HRID 341291Notes

Reaction equation

HRID 341291 reaction equation
[Cl:1][C:2]1[CH:30]=[N:29][C:5]2[N:6]([S:20]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)(=[O:22])=[O:21])[C:7]3[C:12]([C:4]=2[CH:3]=1)=[CH:11][C:10]([C:13]1[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=1)=[CH:9][CH:8]=3.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:50][N:51]1[CH2:56][CH2:55][N:54]([CH2:57][CH2:58]O)[CH2:53][CH2:52]1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1.C1COCC1.CO>[Cl:1][C:2]1[CH:30]=[N:29][C:5]2[N:6]([S:20]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)(=[O:22])=[O:21])[C:7]3[C:12]([C:4]=2[CH:3]=1)=[CH:11][C:10]([C:13]1[CH:18]=[CH:17][C:16]([O:19][CH2:58][CH2:57][N:54]2[CH2:55][CH2:56][N:51]([CH3:50])[CH2:52][CH2:53]2)=[CH:15][CH:14]=1)=[CH:9][CH:8]=3

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 2311841-(2-Hydroxyethyl)-4-methylpiperazineHCID 5363146Diisopropyl azodicarboxylateHCID 461829684-(3-chloro-9-(benzenesulfonyl)-9H-pyrido[2,3-b]indol-6-yl)phenol

Product 1

HCID 461829703-chloro-6-(4-(2-(4-methylpiperazin-1-yl)ethoxy)phenyl)-9-(benzenesulfonyl)-9H-pyrido[2,3-b]indoleYield 80%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 21899815MeOH tetrahydrofuranSolvent

Procedure

To a solution of 4-(3-chloro-9-(benzenesulfonyl)-9H-pyrido[2,3-b]indol-6-yl)phenol (240 mg, 0.55 mmol, 1 equiv.) in anhydrous THF (14 ml), triphenylphosphin (577 mg, 2.2 mmol, 4 equiv.) and 2-(4-methylpiperazin-1-yl)ethanol (397 mg, 2.75 mmol, 5 equiv.) are added. DIAD (445 mg, 2.2 mmol, 4 equiv.) is then added dropwise to the solution which is stirred at room temperature for 12 hours. The mixture is then extracted with a solution of HCl 0.1M (3×10 ml). The aqueous layer is treated with Na2CO3 until pH=9 and then extracted with AcOEt (3×20 ml). The organic layers are dried over MgSO4, filtered and concentrated under reduced pressure. The residue (yellow solid) is purified over silica chromatography (eluted with AcOEt/MeOH 9:1 and then THF/MeOH 9:1) to give the product as a white solid (259 mg, 0.44 mmol) in 80% yield. 1H NMR (300 MHz, CDCl3) δ 8.47 (dd, 2H, J=2.5, 7.7 Hz), 8.17 (d, 1H, J=2.1 Hz), 8.13 (d, 2H, J=7.5 Hz), 8.00 (d, 1H, J=0.9 Hz), 7.76 (dd, 1H, J=1.5, 8.6 Hz), 7.57-7.39 (m, 5H), 7.55 (d, 2H, J=8.6 Hz), 7.01 (d, 2H, J=8.5 Hz), 4.17 (t, 2H, J=5.6 Hz), 2.87 (t, 2H, J=5.6 Hz), 2.70-2.58 (br d, 8H), 2.35 (s, 3H).

Workup

  1. extractionThe mixture is then extracted with a solution of HCl 0.1M (3×10 ml)
  2. additionThe aqueous layer is treated with Na2CO3 until pH=9
  3. extractionextracted with AcOEt (3×20 ml)
  4. dry with materialThe organic layers are dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue (yellow solid) is purified over silica chromatography (
  8. washeluted with AcOEt/MeOH 9:1

Sources & evidence

ORD record
ord-cd2e20b200d0466480647e0215f79cc8
Source dataset
uspto-grants-2014_11
Patent number
US08895744B2

Reaction notes

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