Trimethyl orthovalerate → 2-butyl-6-[2-(3-pyridin-3-ylpropoxy)ethyl]-6H-imidazo[4,5-c]tetrazolo[1,5-a]quinoline

HRID 432706Notes

Reaction equation

HRID 432706 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][CH2:8][CH2:9][O:10][CH2:11][CH2:12][NH:13][C:14]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[N:17]3[N:24]=[N:25][N:26]=[C:16]3[C:15]=2[NH2:27])[CH:2]=1.[C:28](OC)(OC)(OC)[CH2:29][CH2:30][CH2:31]C.Cl.N1C=CC=C[CH:41]=1>C1(C)C=CC=CC=1>[CH2:28]([N:25]1[N:26]=[C:16]2[C:15]3[N:27]=[CH:41][N:13]([CH2:12][CH2:11][O:10][CH2:9][CH2:8][CH2:7][C:3]4[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=4)[C:14]=3[C:23]3[C:18]([N:17]2[NH:24]1)=[CH:19][CH:20]=[CH:21][CH:22]=3)[CH2:29][CH2:30][CH3:31]

Participants

5

Reactant 3

HCID 83755Trimethyl orthovalerateHCID 10176127Pyridinium chlorideHCID 18760199N5-[2-(3-pyridin-3-ylpropoxy)ethyl]tetrazolo[1,5-a]quinoline-4,5-diamine

Product 1

HCID 187601922-butyl-6-[2-(3-pyridin-3-ylpropoxy)ethyl]-6H-imidazo[4,5-c]tetrazolo[1,5-a]quinoline

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Under an atmosphere of nitrogen, N5-[2-(3-pyridin-3-ylpropoxy)ethyl]tetrazolo[1,5-a]quinoline-4,5-diamine (2.48 g, 6.82 mmol) was dissolved in toluene (40 ml). Trimethyl orthovalerate (1.29 ml, 7.51 mmol) was added via syringe. A catalytic amount of pyridine hydrochloride was added to the reaction and the flask was fitted with a Dean-Stark trap. The reaction was heated to reflux and the volatiles were collected in the trap. After 4 hours, the reaction was cooled to room temperature and quenched by the addition of water (30 ml). The phases were separated and the aqueous phase was extracted with ethyl acetate (3×15 ml). The combined organic fractions were washed with brine (25 ml), dried (Na2SO4), filtered and concentrated in vacuo to provide a red/brown oil. The material was purified by flash column chromatography (silica gel, 2/1 to 95/5 ethyl acetate/hexane gradient) to yield 1.98 g of 2-butyl-6-[2-(3-pyridin-3-ylpropoxy)ethyl]-6H-imidazo[4,5-c]tetrazolo[1,5-a]quinoline as an orange oil.

Workup

  1. customthe flask was fitted with a Dean-Stark trap
  2. temperatureThe reaction was heated
  3. temperatureto reflux
  4. customthe volatiles were collected in the trap
  5. customquenched by the addition of water (30 ml)
  6. customThe phases were separated
  7. extractionthe aqueous phase was extracted with ethyl acetate (3×15 ml)
  8. washThe combined organic fractions were washed with brine (25 ml)
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customto provide a red/brown oil
  13. customThe material was purified by flash column chromatography (silica gel, 2/1 to 95/5 ethyl acetate/hexane gradient)

Sources & evidence

ORD record
ord-cff556d33d214ea591fa7ab36568c619
Source dataset
uspto-grants-2003_12
Patent number
US06664260B2

Reaction notes

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