8-chloro-2-methyl-1H,2H,3H,4H,5H-pyrido(4,3-b)indole → HCID 59455049, compound

HRID 1400535Notes

Reaction equation

HRID 1400535 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[NH:7][C:6]3[CH2:11][CH2:12][N:13]([CH3:15])[CH2:14][C:5]=3[C:4]=2[CH:3]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].N1CCC[C@H]1C(O)=O.Br[CH:33]=[C:34]([CH:36]1[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]1)[CH3:35]>CN(C=O)C.[Cu]I>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7](/[CH:33]=[C:34](\[CH:36]3[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]3)/[CH3:35])[C:6]3[CH2:11][CH2:12][N:13]([CH3:15])[CH2:14][C:5]=3[C:4]=2[CH:3]=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 86644764HCID 86644764, compound

Product 1

HCID 59455049HCID 59455049, compound

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
85 °C

Procedure

8-Chloro-2,3,4,5-tetrahydro-2-methyl-1H-pyrido[4,3-b]indole (110 mg, 0.5 mmol) was dissolved in DMF (3 mL). Potassium phosphate (212.4 mg, 1 mmol), copper (I) iodide (9.5 mg, 0.05 mmol) and L-proline (11.51 mg, 0.1 mmol) were added. (1-Bromoprop-1-en-2-yl)cyclohexane (121.8 mg, 0.6 mmol) was dissolved in DMF (2 mL) and added dropwise to the reaction mixture. Nitrogen was purged for 2 min and the reaction mixture heated at 85° C. overnight (prolonged heating required in some cases). DMF was evaporated and water added. The precipitate obtained was filtered and crude Compound was purified by silica gel chromatography (100-200 mesh) using 0-3% MeOH:DCM as eluent. The compound was further purified through reverse phase purification. Yield: 6 mg. 1H NMR (CD3OD, TFA salt) δ (ppm): 7.50 (s, 1H), 7.18(d, 1H), 7.10 (d, 1H), 6.42 (s, 1H), 4.70 (m, 1H), 4.38 (m, 1H), 3.82 (m, 1H), 3.58 (m, 1H), 3.10 (s, 3H), 3.05 (m, 2H), 2.30 (m, 1H), 1.90 (m, 4H), 1.78 (m, 1H), 1.42-1.30 (m, 8H).

Workup

  1. additionadded dropwise to the reaction mixture
  2. customNitrogen was purged for 2 min
  3. temperatureprolonged heating
  4. customDMF was evaporated
  5. additionwater added
  6. customThe precipitate obtained
  7. filtrationwas filtered
  8. customcrude Compound was purified by silica gel chromatography (100-200 mesh)
  9. customThe compound was further purified through reverse phase purification

Sources & evidence

ORD record
ord-5df6328a57364ba6b1e73c231f68a001
Source dataset
uspto-grants-2014_12
Patent number
US08906925B2

Reaction notes

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