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

HRID 1499049Notes

Reaction equation

HRID 1499049 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.N1C=C[CH:26]=[C:25](B(O)O)[CH:24]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH3:40][N:41]([CH:43]=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:2]=[CH:26][CH:25]=[CH:24][C:4]=3[C:5]3[CH:40]=[N:41][CH:43]=[CH:7][CH:6]=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 4

HCID 62657Potassium Phosphate, TribasicHCID 27343783-Pyridinylboronic acidHCID 21962138N,N-Dimethylformamide--water (1/1)HCID 673790385-(2-bromo-phenyl)-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

Product 1

HCID 673791612,8-dimethyl-5-(2-pyridin-3-yl-phenyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent

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 (100 mg, 0.282 mmol), 3-pyridinylboronic acid (51 mg, 0.420 mmol) and K3PO4 (149 mg, 0.706 mmol) in DMF-water (4:1 mL) was added PdCl2(PPh3)2 (10 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-3-yl-phenyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole as a semisolid (30 mg). 1H NMR (Oxalate salt, CD3OD) δ (ppm): 8.30 (s, 1H), 8.10 (s, 1H), 7.70 (m, 3H), 7.56 (d, 1H), 7.50 (d, 1H), 7.24 (m, 2H), 6.98 (d, 1H), 6.82 (d, 1H), 4.50 (m, 2H), 3.60 (m, 2H), 3.05 (s, 3H), 2.95 (m, 1H), 2.62 (m, 1H), 2.40 (s, 3H).

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-fc2a48b9e04349a6ab2acf6b5ce773f2
Source dataset
uspto-grants-2015_12
Patent number
US09199985B2

Reaction notes

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