Potassium Phosphate, Tribasic → HCID 53372996, compound

HRID 1401538Notes

Reaction equation

HRID 1401538 reaction equation
[F:1][C:2]1[C:3]([F:16])=[CH:4][C:5]2[C:6]3[CH2:14][N:13]([CH3:15])[CH2:12][CH2:11][C:7]=3[NH:8][C:9]=2[CH:10]=1.N1CCC[C@H]1C(O)=O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[CH:34]=[C:35]([C:37]1[CH:38]=[CH:39][C:40]([CH3:43])=[N:41][CH:42]=1)[CH3:36]>CN(C=O)C.[Cu]I>[F:1][C:2]1[C:3]([F:16])=[CH:4][C:5]2[C:6]3[CH2:14][N:13]([CH3:15])[CH2:12][CH2:11][C:7]=3[N:8](/[CH:34]=[C:35](/[C:37]3[CH:42]=[N:41][C:40]([CH3:43])=[CH:39][CH:38]=3)\[CH3:36])[C:9]=2[CH:10]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 145742L-ProlineHCID 67311268HCID 67311268, compoundHCID 866447585-(2-Bromo-1-methyl-vinyl)-2-methyl-pyridine

Product 1

HCID 53372996HCID 53372996, compound

Reagents, catalysts & solvents 2

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

Procedure

7,8-Difluoro-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (177 mg, 0.8 mmol) was dissolved in DMF (5 mL). Copper (I) iodide (19 mg, 0.10 mmol), L-proline (23 mg, 0.20 mmol) and potassium phosphate (424 mg, 2 mmol) were added and the reaction mixture was stirred for 10 min. at RT. 5-(1-Bromoprop-1-en-2-yl)-2-methylpyridine (212 mg, 1 mmol) was added dropwise and the reaction mixture was purged with nitrogen. The reaction mixture was heated overnight at 80° C. (prolonged heating in some cases was required). DMF was evaporated under reduced pressure, the residue was diluted with water and the solid was filtered. The solid material was purified by silica gel chromatography (100-200 mesh). The product was further purified by HPLC. 1H NMR (CDCl3, TFA salt) δ (ppm): 9.10 (s, 1H), 8.22 (d, 1H), 7.60 (d, 1H), 7.15 (t, 1H), 7.02 (s, 1H), 6.95 (t, 1H), 4.70 (m, 1H), 4.10 (m, 1H), 3.90 (m, 1H), 3.30 (m, 2H), 3.05 (s, 3H), 2.90 (m, 1H), 2.80 (s, 3H), 2.0 (s, 3H).

Workup

  1. customthe reaction mixture was purged with nitrogen
  2. temperatureThe reaction mixture was heated overnight at 80° C. (
  3. temperatureprolonged heating in some cases
  4. customDMF was evaporated under reduced pressure
  5. additionthe residue was diluted with water
  6. filtrationthe solid was filtered
  7. customThe solid material was purified by silica gel chromatography (100-200 mesh)
  8. customThe product was further purified by HPLC

Sources & evidence

ORD record
ord-d489aaffae9647e59914ba7ed838b4a2
Source dataset
uspto-grants-2014_12
Patent number
US08907097B2

Reaction notes

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