Phosphorus pentachloride → HCID 58329529, compound

HRID 1043866Notes

Reaction equation

HRID 1043866 reaction equation
[C:1]1([C:13]([NH:15][CH:16]2[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]2)=O)[C:11]2=[C:12]3[C:7](=[CH:8][CH:9]=[CH:10]2)[CH2:6][CH2:5][CH2:4][N:3]3[CH:2]=1.P(Cl)(Cl)(Cl)(Cl)[Cl:30].C[Si]([N:39]=[N+:40]=[N-:41])(C)C.C([O-])(O)=O.[Na+]>>[ClH:30].[NH:19]1[CH2:20][CH2:21][CH:16]([N:15]2[C:13]([C:1]3[C:11]4=[C:12]5[C:7](=[CH:8][CH:9]=[CH:10]4)[CH2:6][CH2:5][CH2:4][N:3]5[CH:2]=3)=[N:41][N:40]=[N:39]2)[CH2:17][CH2:18]1.[C:1]1([C:13]2[N:15]([CH:16]3[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]3)[N:41]=[N:40][N:39]=2)[C:11]2=[C:12]3[C:7](=[CH:8][CH:9]=[CH:10]2)[CH2:6][CH2:5][CH2:4][N:3]3[CH:2]=1

Participants

6

Reactant 4

HCID 24819Phosphorus pentachlorideHCID 78378AzidotrimethylsilaneHCID 516892Sodium BicarbonateHCID 67249826HCID 67249826, compound

Product 2

HCID 58329529HCID 58329529, compoundHCID 67250176HCID 67250176, compound

Procedure

To a solution of 5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-1-carboxylic acid (200 mg, 1.00 mmol) in dry N,N-dimethylformamide (3 mL) were added O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HBTU) (417 mg, 1.10 mmol) and disopropylethyl amine (0.35 mL, 2.0 mmol), and tert-butyl 4-aminopiperidine-1-carboxylate (1.00 mmol). The reaction was stirred at room temperature and monitored by LC-MS. Upon completion, the mixture was diluted with ethyl acetate (50 mL) and washed with water (25 mL), sat. NaHCO3 solution (25 mL) and brine. The organic phase was separated and dried over sodium sulfate. After removing solvent, the crude product was purified by silica gel chromatography (EtOAc/Hexanes) to give the desired product tert-butyl 4-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-1-carboxamido)piperidine-1-carboxylate (77) as a white solid. Mp=187-189° C., LC/MS [M+H]: 384.22. Step 2: Amide (77) (1 eq), was dissolved in dicholoromethane (15 mL/1 mmol) and phosphorus pentachloride (1 eq) was added. The mixture was stirred at ambient temperature for 2 hours then trimethylsilyl azide (8 eq) was added. Mixture was stirred at room temperature for additional 4 hours and reaction progress was followed by LC-MS. Upon completion, saturated NaHCO3 solution was added and the mixture was extracted with dicholoromethane (30 mL/mol), Combined organics were combined and dried Na2SO4 Solvent was removed and the crude product was purified by silica gel chromatography (EtOAc/Hexanes, 25-40% gradient) to give the desired product tert-butyl 4-(5-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-1H-tetrazol-1-yl)piperidine-1-carboxylate (78) as a solid. LC/MS [M+H]: 409.23. Step 3: Carbamate (78) (1 equivalent) was dissolved in dicholoromethane and HCl (20 equivalent, 4 M in dioxane) was added and stirred at room temperature for 2 to 4 hours. Concentration of the solution under reduced pressure gave the pure desired product 1-(1-(piperidin-4-yl)-1H-tetrazol-5-yl)-5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinoline hydrochloride (79) as a white solid Mp=198-200° C., LC/MS [M+H]: 309.18.

Workup

  1. additionwas added
  2. stirringMixture was stirred at room temperature for additional 4 hours
  3. customreaction progress
  4. extractionthe mixture was extracted with dicholoromethane (30 mL/mol)
  5. customdried Na2SO4 Solvent was removed
  6. customthe crude product was purified by silica gel chromatography (EtOAc/Hexanes, 25-40% gradient)

Sources & evidence

ORD record
ord-79d59aa24b834f02ac45342a7a6a06b4
Source dataset
uspto-grants-2013_10
Patent number
US08563567B2

Reaction notes

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