8-chloro-2-methyl-1H,2H,3H,4H,5H-pyrido(4,3-b)indole → HCID 59455200, compound

HRID 1400592Notes

Reaction equation

HRID 1400592 reaction equation
Br[CH:2]=[C:3]([C:5]1[CH:6]=[CH:7][C:8]([O:11][CH3:12])=[N:9][CH:10]=1)[CH3:4].P([O-])([O-])([O-])=O.[K+].[K+].[K+].N1CCC[C@H]1C(O)=O.[Cl:29][C:30]1[CH:38]=[CH:37][C:36]2[NH:35][C:34]3[CH2:39][CH2:40][N:41]([CH3:43])[CH2:42][C:33]=3[C:32]=2[CH:31]=1>CN(C=O)C.[Cu]I>[Cl:29][C:30]1[CH:38]=[CH:37][C:36]2[N:35](/[CH:2]=[C:3](/[C:5]3[CH:10]=[N:9][C:8]([O:11][CH3:12])=[CH:7][CH:6]=3)\[CH3:4])[C:34]3[CH2:39][CH2:40][N:41]([CH3:43])[CH2:42][C:33]=3[C:32]=2[CH:31]=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 86644773HCID 86644773, compound

Product 1

HCID 59455200HCID 59455200, compound

Reagents, catalysts & solvents 2

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

Conditions

Temperature
85 °C

Procedure

5-(1-Bromoprop-1-en-2-yl)-2-methoxypyridine (113 mg, 0.5 mmol) was dissolved in DMF (2 mL) and potassium phosphate (212 mg, 1 mmol) was added followed by copper (I) iodide (9 mg, 0.05 mmol) and L-proline (11.5 mg, 0.1 mmol). 8-chloro-2,3,4,5-tetrahydro-2-methyl-1H-pyrido[4,3-b]indole (110 mg, 0.5 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 product was purified on silica gel (100-200 mesh) using 0-4% MeOH:DCM as eluent. The compound was further purified through reverse phase HPLC. Yield: 15 mg. 1H NMR (CD3OD, oxalate salt) δ (ppm): 8.40 (s, 1H), 7.98 (d, 1H), 7.56 (s, 1H), 7.22 (s, 2H), 7.0 (s, 1H), 6.84 (d, 1H), 4.50 (s, 2H), 3.96 (s, 3H), 3.70 (m, 2H), 3.18 (m, 2H), 3.12 (s, 3H), 1.96 (s, 3H).

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 product was purified on silica gel (100-200 mesh)
  5. customThe compound was further purified through reverse phase HPLC

Sources & evidence

ORD record
ord-810bdd5e2f614327a2c1dccf6e53c2c1
Source dataset
uspto-grants-2014_12
Patent number
US08906925B2

Reaction notes

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