8-chloro-2-methyl-1H,2H,3H,4H,5H-pyrido(4,3-b)indole → HCID 46199733, compound

HRID 1400537Notes

Reaction equation

HRID 1400537 reaction equation
Br[CH:2]=[C:3]([C:5]1[CH:10]=[CH:9][N:8]=[CH:7][CH:6]=1)[CH3:4].P([O-])([O-])([O-])=O.[K+].[K+].[K+].N1CCC[C@H]1C(O)=O.[Cl:27][C:28]1[CH:36]=[CH:35][C:34]2[NH:33][C:32]3[CH2:37][CH2:38][N:39]([CH3:41])[CH2:40][C:31]=3[C:30]=2[CH:29]=1>[Cu]I.CN(C=O)C>[Cl:27][C:28]1[CH:36]=[CH:35][C:34]2[N:33](/[CH:2]=[C:3](\[C:5]3[CH:10]=[CH:9][N:8]=[CH:7][CH:6]=3)/[CH3:4])[C:32]3[CH2:37][CH2:38][N:39]([CH3:41])[CH2:40][C:31]=3[C:30]=2[CH:29]=1

Participants

7

Reactant 4

HCID 196158-chloro-2-methyl-1H,2H,3H,4H,5H-pyrido(4,3-b)indoleHCID 62657Potassium Phosphate, TribasicHCID 145742L-ProlineHCID 86642478(E)-4-(1-bromoprop-1-en-2-yl)pyridine

Product 1

HCID 46199733HCID 46199733, compound

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

4-(1-Bromoprop-1-en-2-yl)pyridine (346 mg, 1.75 mmol) was adsorbed in potassium phosphate (617 mg, 2.9 mmol) and DMF (5 mL) was added followed by copper (I) iodide (27 mg, 0.145 mmol) and L-proline (33 mg, 0.29 mmol). 8-Chloro-2,3,4,5-tetrahydro-2-methyl-1H-pyrido[4,3-b]indole (321 mg, 1.45 mmol) was added to the reaction mixture and nitrogen gas purged for 2 min. The reaction mixture was stirred at 100° C. for 12 h. The reaction mixture was cooled to RT and water (20 mL) was added. The compound was extracted with EtOAc (3×50 mL). The organic layer was washed with water (2×50 mL) and compound was purified through silica gel (100-200 mesh) using 0-5% MeOH:DCM as eluent and further purified through reverse phase HPLC. Yield: 46 mg. 1H NMR (DMSO, D1-HCl salt) δ (ppm): 8.60 (d, 2H), 7.55 (s, 1H), 7.50 (d, 2H), 7.30 (s, 1H), 7.12 (d, 1H), 7.02 (d, 1H), 4.50 (m, 1H), 4.20 (m, 1H), 3.60 (m, 1H), 3.38 (m, 1H), 2.85 (m, 2H), 2.80 (s, 3H), 2.36 (s, 3H).

Workup

  1. custompurged for 2 min
  2. temperatureThe reaction mixture was cooled to RT
  3. additionwater (20 mL) was added
  4. extractionThe compound was extracted with EtOAc (3×50 mL)
  5. washThe organic layer was washed with water (2×50 mL) and compound
  6. customwas purified through silica gel (100-200 mesh)
  7. customDCM as eluent and further purified through reverse phase HPLC

Sources & evidence

ORD record
ord-5d02735d286946b081c7adec7f9e5598
Source dataset
uspto-grants-2014_12
Patent number
US08906925B2

Reaction notes

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