8-chloro-2-methyl-1H,2H,3H,4H,5H-pyrido(4,3-b)indole → HCID 59454889, compound

HRID 1400599Notes

Reaction equation

HRID 1400599 reaction equation
Br[CH:2]=[C:3]([C:10]1[CH:15]=[CH:14][N:13]=[CH:12][CH:11]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].N1CCC[C@H]1C(O)=O.[Cl:32][C:33]1[CH:41]=[CH:40][C:39]2[NH:38][C:37]3[CH2:42][CH2:43][N:44]([CH3:46])[CH2:45][C:36]=3[C:35]=2[CH:34]=1>CN(C=O)C.[Cu]I>[Cl:32][C:33]1[CH:41]=[CH:40][C:39]2[N:38](/[CH:2]=[C:3](/[C:4]3[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=3)\[C:10]3[CH:15]=[CH:14][N:13]=[CH:12][CH:11]=3)[C:37]3[CH2:42][CH2:43][N:44]([CH3:46])[CH2:45][C:36]=3[C:35]=2[CH:34]=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 86644776HCID 86644776, compound

Product 1

HCID 59454889HCID 59454889, compound

Reagents, catalysts & solvents 2

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

Conditions

Temperature
85 °C

Procedure

4-(2-Bromo-1-phenylvinyl)pyridine (310 mg, 1.1 mmol) was dissolved in DMF (5 mL) and potassium phosphate (424 mg, 2 mmol) was added followed by copper (I) iodide (19 mg, 0.1 mmol) and L-proline (23 mg, 0.2 mmol). 8-Chloro-2,3,4,5-tetrahydro-2-methyl-1H-pyrido[4,3-b]indole (220 mg, 1 mmol) was added and the mixture purged with nitrogen for 2 min. The reaction mixture was stirred at 85° C. overnight. Water was added and the solid mass was filtered under vacuum. The crude compound was purified on silica gel (100-200 mesh) using 0-10% MeOH:DCM as eluent. The compound was further purified through reverse phase HPLC. Yield: 21 mg (TFA salt). 1H NMR (CDCl3, TFA salt) δ (ppm): 8.58 (d, 2H), 7.50 (m, 2H), 7.36-7.18 (m, 7H), 7.08 (d, 1H), 6.90 (d, 1H), 4.65 (m, 1H), 4.05 (m, 1H), 3.80 (m, 1H), 3.30 (m, 2H), 3.0 (s, 3H), 2.80 (m, 1H).

Workup

  1. customthe mixture purged with nitrogen for 2 min
  2. additionWater was added
  3. filtrationthe solid mass was filtered under vacuum
  4. customThe crude compound was purified on silica gel (100-200 mesh)
  5. customThe compound was further purified through reverse phase HPLC

Sources & evidence

ORD record
ord-b399a2a4fea64cbc941013582968033b
Source dataset
uspto-grants-2014_12
Patent number
US08906925B2

Reaction notes

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