Potassium Phosphate, Tribasic → HCID 51001929, compound

HRID 2167813Notes

Reaction equation

HRID 2167813 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]1[CH2:11][CH:12]3[N:16]([CH2:17][C:5]2=1)[CH2:15][CH2:14][CH2:13]3.N1CCC[C@H]1C(O)=O.[O-]P([O-])([O-])=O.[K+].[K+].[K+].Br[CH:35]=[C:36]([C:38]1[CH:43]=[CH:42][C:41]([F:44])=[CH:40][CH:39]=1)[CH3:37]>CN(C=O)C.[Cu]I>[F:44][C:41]1[CH:42]=[CH:43][C:38](/[C:36](/[CH3:37])=[CH:35]/[N:7]2[C:8]3[C:4](=[CH:3][C:2]([CH3:1])=[CH:10][CH:9]=3)[C:5]3[CH2:17][N:16]4[CH:12]([CH2:11][C:6]2=3)[CH2:13][CH2:14][CH2:15]4)=[CH:39][CH:40]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 145742L-ProlineHCID 67434536HCID 67434536, compoundHCID 86644757(1-Bromoprop-1-en-2-yl)-4-fluorobenzene

Product 1

HCID 51001929HCID 51001929, compound

Reagents, catalysts & solvents 2

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

Procedure

7-Methyl-2,3,5,10,11,11a-hexahydro-1H-indolizino[7,6-b]indole (45 mg, 0.198 mmol) was dissolved in DMF (5 mL). Copper (I) iodide (3.76 mg, 0.0198 mmol), L-proline (2.1 mg, 0.0398 mmol) and K3PO4 (71 mg, 0.396 mmol) were added and the reaction mixture was stirred for min at RT. 1-(1-Bromoprop-1-en-2-yl)-4-fluorobenzene (51 mg, 0.24 mmol) was added dropwise and the reaction mixture was purged with nitrogen. The reaction mixture was heated at 85° C. overnight (prolonged heating in some cases was required). The 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) eluting with 0-5% MeOH-DCM. The product was further purified by reverse phase HPLC. Yield: 22 mg as TFA salt; Column: YMC ODS AQ, 4.6×250 mm, 5 μm, Mobile Phase, Mobile Phase A: 0.05% TFA, Mobile Phase B: Acetonitrile, Gradient, 10% to 90% B in 10 min, hold for 10 min, 90% to 10% B in 1 min, Flow Rate: 1.0 mL/min, Retention time: 10.094 min, HPLC purity: 98.06%;

Workup

  1. customthe reaction mixture was purged with nitrogen
  2. temperatureThe reaction mixture was heated at 85° C. overnight (
  3. temperatureprolonged heating in some cases
  4. customThe DMF 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. washeluting with 0-5% MeOH-DCM
  9. customThe product was further purified by reverse phase HPLC
  10. waithold for 10 min
  11. wait90% to 10% B in 1 min

Sources & evidence

ORD record
ord-67e2dfa1c4bf42c4a2f4604bdf38abbf
Source dataset
uspto-grants-2015_06
Patent number
US09045482B2

Reaction notes

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