Oxalic Acid → HCID 59454955, compound

HRID 1400491Notes

Reaction equation

HRID 1400491 reaction equation
[CH3:1][CH:2]1[C:14]2[C:13]3[CH:12]=[C:11]([CH3:15])[CH:10]=[CH:9][C:8]=3[NH:7][C:6]=2[CH2:5][CH:4]([CH3:16])[N:3]1[CH3:17].P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[CH:27]=[C:28]([C:33]1[CH:38]=[CH:37][N:36]=[CH:35][CH:34]=1)[C:29](C)(C)C.C(O)(=O)C(O)=O>CN(C=O)C.C1COCC1.N1CCC[C@H]1C(O)=O.[Cu]I>[CH3:1][CH:2]1[C:14]2[C:13]3[CH:12]=[C:11]([CH3:15])[CH:10]=[CH:9][C:8]=3[N:7](/[CH:27]=[C:28](/[C:33]3[CH:38]=[CH:37][N:36]=[CH:35][CH:34]=3)\[CH3:29])[C:6]=2[CH2:5][CH:4]([CH3:16])[N:3]1[CH3:17]

Participants

8

Reactant 4

HCID 971Oxalic AcidHCID 62657Potassium Phosphate, TribasicHCID 67309717HCID 67309717, compoundHCID 86644760HCID 86644760, compound

Product 1

HCID 59454955HCID 59454955, compound

Reagents, catalysts & solvents 3

HCID 67304547HCID 67304547, compoundCatalystHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

2,3,4,5-Tetrahydro-1,2,3,8-tetramethyl-1H-pyrido[4,3-b]indole (550 mg, 2 mmol) was dissolved in DMF. Copper (I) iodide L-proline (46 mg, 0.4 mmol) and potassium phosphate (848 mg, 4 mmol) were added and the reaction mixture was stirred for 10 min. at RT. 4-(1-bromo-3,3-dimethylbut-1-en-2-yl)pyridine (294 mg, 3.0 mmol) was added dropwise and the reaction mixture was purged with nitrogen. The reaction mixture was heated overnight at 85° 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. The free base was converted into oxalate salt by treatment of oxalic acid (1 equiv) in THF. Yield: 8 mg as the oxalate salt. 1H NMR (CD3OD, freebase) δ (ppm): 8.60 (d, 2H), 7.70 (d, 2H), 7.35 (s, 1H), 7.30 (s, 1H), 7.10 (m, 2H), 4.50 (m, 1H), 4.0 (m, 1H), 3.10 (m, 1H), 2.90 (s, 3H), 2.80 (m, 1H), 2.42 (s, 3H), 2.0 (s, 3H), 1.76 (d, 3H), 1.50 (d, 3H).

Workup

  1. customthe reaction mixture was purged with nitrogen
  2. temperatureThe reaction mixture was heated overnight at 85° 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-f4b5ff8540b640499c2bf99b0162b270
Source dataset
uspto-grants-2014_12
Patent number
US08906925B2

Reaction notes

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