Potassium Phosphate, Tribasic → Hydrochloric Acid

HRID 2198344Notes

Reaction equation

HRID 2198344 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]1[CH2:11][N:12]([CH3:15])[CH2:13][CH2:14][C:5]2=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[Cl:24][CH2:25][C:26]([N:28]1[CH2:33][CH2:32][N:31](C(OC(C)(C)C)=O)[CH2:30][CH2:29]1)=[O:27]>CN(C)C=O.Cl.C(O)C.[Cu]I.N1CCC[C@H]1C(O)=O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:25][C:26]([N:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1)=[O:27])[C:6]1[CH2:11][N:12]([CH3:15])[CH2:13][CH2:14][C:5]2=1.[ClH:24]

Participants

10

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 155083736-chloro-2-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indoleHCID 15829156Tert-butyl 4-(2-chloroacetyl)piperazine-1-carboxylate

Product 2

HCID 313Hydrochloric AcidYield 487.6%HCID 44242646HCID 44242646, compound

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 145742L-ProlineCatalystHCID 313Hydrochloric AcidSolventHCID 702EthanolSolventHCID 6228DimethylformamideSolvent

Procedure

6-chloro-2-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole (100 mg, 0.45 mmol), was dissolved in N,N-dimethylformamide. CuI (9 mg, 0.045 mmol), L-proline (11 mg, 0.091 mmol), and K3PO4 (194 mg, 0.91 mmol) was added to the reaction mixture and stirred for 10 min at room temperature, followed by drop-wise addition of tert-butyl 4-(2-chloroacetyl)piperazine-1-carboxylate (143 mg, 0.54 mmol) and stirred at 90° C. for 12 h. After completion of the reaction, the reaction mixture was filtered through Celite, N,N-dimethylformamide was evaporated under reduced pressure and extracted with ethyl acetate. The combined organic layer was dried over Na2SO4, and concentrated under reduced pressure. The crude compound was purified by Column chromatography to give Boc-protected compound (0.150 mg). The compound was dissolved in HCl in ethanol (4 mL). The ethanol was evaporated to obtain 2-(6-chloro-2-methyl-3,4-dihydro-1H-pyrido[3,4-b]indol-9(2H)-yl)-1-(piperazin-1-yl)ethanone as HCl salt (80 mg). 1 H NMR (CD3OD): 7.52 (s, 1H), 7.24 (d, 1H), 7.15 (dd, 1H), 5.19-5.23 (m, 2H), 4.71-4.79 (m, 2H), 4.25-4.30 (m, 2H), 3.85-4.00 (m, 4H), 3.70-3.79 (m, 2H), 3.52 (s, 3H), 3.15-3.23 (m, 4H).

Workup

  1. stirringstirred at 90° C. for 12 h
  2. customAfter completion of the reaction
  3. filtrationthe reaction mixture was filtered through Celite, N,N-dimethylformamide
  4. customwas evaporated under reduced pressure
  5. extractionextracted with ethyl acetate
  6. dry with materialThe combined organic layer was dried over Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customThe crude compound was purified by Column chromatography
  9. customto give Boc-protected compound (0.150 mg)
  10. customThe ethanol was evaporated

Sources & evidence

ORD record
ord-8ae323867f334eb19d5464fb85000c58
Source dataset
uspto-grants-2012_12
Patent number
US08338447B2

Reaction notes

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