Triethylamine → (7-benzyloxy-3-nitroquinolin-4-yl)(tetrahydro-2H-pyran-4-ylmethyl)amine

HRID 540924Notes

Reaction equation

HRID 540924 reaction equation
[CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13](O)=[C:14]([N+:19]([O-:21])=[O:20])[CH:15]=[N:16]2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.P(Cl)(Cl)(Cl)=O.C(N(CC)CC)C.[O:35]1[CH2:40][CH2:39][CH:38]([CH2:41][NH2:42])[CH2:37][CH2:36]1>CN(C=O)C.ClCCl>[CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([NH:42][CH2:41][CH:38]3[CH2:39][CH2:40][O:35][CH2:36][CH2:37]3)=[C:14]([N+:19]([O-:21])=[O:20])[CH:15]=[N:16]2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 24813Phosphorus oxychlorideHCID 27732104-AminomethyltetrahydropyranHCID 178526778HCID 178526778, compound

Product 1

HCID 67051153(7-benzyloxy-3-nitroquinolin-4-yl)(tetrahydro-2H-pyran-4-ylmethyl)amineYield 86.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

7-(Benzyloxy)-3-nitroquinolin-4-ol (12.3 g, 41.6 mmol) was slurried in DMF (83 mL). Phosphorous oxychloride (4.2 mL, 45 mmol) was added in one portion and the mixture was heated at 100° C. for 5 minutes. The solution was allowed to cool to 40° C. and was then poured into ice water (total volume 400 mL) resulting in a tan precipitate. The precipitate was filtered and washed with water. After drying, the solid was dissolved in dichloromethane and the residual water was separated. The organic fraction was dried over anhydrous sodium sulfate and anhydrous magnesium sulfate (about a 50/50 mixture). The organic fraction was filtered into a reaction flask (total volume of organic with 7-(benzyloxy)-3-chloro-4-nitroquinoline is about 425 mL). The flask was cooled to 8° C. and triethylamine (11.6 mL, 83.0 mmol) was added. (Tetrahydro-2H-pyran-4-yl)methylamine (6.0 g, 52 mmol) in dichloromethane (50 mL) was added dropwise to the mixture. The cooling bath was removed and the reaction was stirred for 16 hours. Water (200 mL) was added followed by stirring for 30 minutes. The layers were separated and the organic fraction was sequentially washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. Recrystallization from 2-propanol afforded 14.1 g of 7-(benzyloxy)-3-nitro-N-(tetrahydro-2H-pyran-4-ylmethyl)quinolin-4-amine as a yellow powder.

Workup

  1. temperatureto cool to 40° C.
  2. customresulting in a tan precipitate
  3. filtrationThe precipitate was filtered
  4. washwashed with water
  5. customAfter drying
  6. dissolutionthe solid was dissolved in dichloromethane
  7. customthe residual water was separated
  8. dry with materialThe organic fraction was dried over anhydrous sodium sulfate and anhydrous magnesium sulfate (about a 50/50 mixture)
  9. filtrationThe organic fraction was filtered into a reaction flask (total volume of organic with 7-(benzyloxy)-3-chloro-4-nitroquinoline is about 425 mL)
  10. temperatureThe flask was cooled to 8° C.
  11. customThe cooling bath was removed
  12. additionWater (200 mL) was added
  13. stirringby stirring for 30 minutes
  14. customThe layers were separated
  15. washthe organic fraction was sequentially washed with saturated aqueous sodium chloride
  16. dry with materialdried over anhydrous sodium sulfate
  17. filtrationfiltered
  18. concentrationconcentrated under reduced pressure
  19. customRecrystallization from 2-propanol

Sources & evidence

ORD record
ord-a76438e79d4a4cd6b222d3a25d5fcf65
Source dataset
uspto-grants-2014_10
Patent number
US08871782B2

Reaction notes

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