Potassium Phosphate, Tribasic → 2,8-dimethyl-5-(2-pyridin-4-yl-phenyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

HRID 715153Notes

Reaction equation

HRID 715153 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:16]2[CH:15]=[CH:14][C:13]([CH3:17])=[CH:12][C:11]=2[C:10]2[CH2:18][N:19]([CH3:22])[CH2:20][CH2:21][C:9]1=2.[N:23]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][CH:24]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.O.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:22][N:19]1[CH2:20][CH2:21][C:9]2[N:8]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[C:26]3[CH:27]=[CH:28][N:23]=[CH:24][CH:25]=3)[C:16]3[CH:15]=[CH:14][C:13]([CH3:17])=[CH:12][C:11]=3[C:10]=2[CH2:18]1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 2734379(Pyridin-4-yl)boronic acidHCID 673790385-(2-bromo-phenyl)-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

Product 1

HCID 601651122,8-dimethyl-5-(2-pyridin-4-yl-phenyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoleYield 7.8%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 21962138N,N-Dimethylformamide--water (1/1)Solvent

Conditions

Temperature
95 °C

Procedure

To a de-aerated solution of 5-(2-bromo-phenyl)-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (180 mg, 0.508 mmol), 4-pyridinylboronic acid (93.8 mg, 0.762 mmol) and K3PO4 (270 mg, 1.27 mmol) in DMF-water (9:1 mL) was added PdCl2(PPh3)2 (18 mg, 5 mol %). The reaction mixture was heated at 95° C. for 30 min under nitrogen atmosphere. The reaction mixture was diluted with water and extracted with EtOAc. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford crude material, which was purified by reverse phase HPLC to yield 2,8-dimethyl-5-(2-pyridin-4-yl-phenyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole as semisolid (14 mg). 1H NMR (Freebase, CDCl3) d (ppm): 8.38 (d, 2H), 7.58 (m, 3H), 7.40 (d, 1H), 7.20 (s, 1H), 6.90 (m, 4H), 3.75 (m, 2H), 2.76 (m, 1H), 2.60 (m, 1H), 2.50 (m, 1H), 2.48 (s, 3H), 2.42 (s, 3H), 2.20 (m, 1H).

Workup

  1. extractionextracted with EtOAc
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customto afford crude material, which
  5. customwas purified by reverse phase HPLC

Sources & evidence

ORD record
ord-14175c7e65e94f0d8f111b43c678e47e
Source dataset
uspto-grants-2015_11
Patent number
US09187471B2

Reaction notes

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