Phosgene → (4-difluoromethylene-3,4-dihydro-2H-quinolin-1-yl)(3-(pyridin-3-yl)pyrrolidin-1-yl)methanone

HRID 551823Notes

Reaction equation

HRID 551823 reaction equation
[F:1][C:2]([F:13])=[C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][CH2:5][CH2:4]1.C(N(CC)CC)C.[C:21](Cl)(Cl)=[O:22].[NH:25]1[CH2:29][CH2:28][CH:27]([C:30]2[CH:31]=[N:32][CH:33]=[CH:34][CH:35]=2)[CH2:26]1>C1(C)C=CC=CC=1.ClCCl>[F:13][C:2]([F:1])=[C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[N:6]([C:21]([N:25]2[CH2:29][CH2:28][CH:27]([C:30]3[CH:31]=[N:32][CH:33]=[CH:34][CH:35]=3)[CH2:26]2)=[O:22])[CH2:5][CH2:4]1

Participants

7

Reactant 4

HCID 6371PhosgeneHCID 8471TriethylamineHCID 36136513-(Pyrrolidin-3-yl)pyridineHCID 671881714-Difluoromethylene-1,2,3,4-tetrahydroquinoline

Product 1

HCID 67188494(4-difluoromethylene-3,4-dihydro-2H-quinolin-1-yl)(3-(pyridin-3-yl)pyrrolidin-1-yl)methanone

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent2×

Procedure

0.07 g of 4-difluoromethylene-1,2,3,4-tetrahydroquinoline and 5 ml of dichloromethane are introduced into a three-necked flask equipped with a magnetic stirrer and placed under an inert atmosphere. After cooling to +4° C., 0.11 ml of triethylamine and 0.39 ml of a 20% solution of phosgene in toluene are successively added. The reaction medium is stirred at ambient temperature for 2 h. The reaction medium is cooled in an ice bath and 0.08 g of 3-(pyrrolidin-3-yl)pyridine in 2 ml of dichloromethane is then introduced. The mixture is stirred at ambient temperature for 18 h. The reaction medium is washed with a 1N sodium hydroxide solution; the organic phase is dried over sodium sulfate and concentrated under reduced pressure. The residue is chromatographed on silica gel eluted with a dichloromethane/methanol 98/2 mixture. 0.05 g of (4-difluoromethylene-3,4-dihydro-2H-quinolin-1-yl)(3-(pyridin-3-yl)pyrrolidin-1-yl)methanone is obtained and is treated with fumaric acid in an ethanol/diisopropyl ether mixture to give the fumarate.

Workup

  1. customequipped with a magnetic stirrer
  2. temperatureAfter cooling to +4° C.
  3. temperatureThe reaction medium is cooled in an ice bath
  4. stirringThe mixture is stirred at ambient temperature for 18 h
  5. washThe reaction medium is washed with a 1N sodium hydroxide solution
  6. dry with materialthe organic phase is dried over sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue is chromatographed on silica gel
  9. washeluted with a dichloromethane/methanol 98/2 mixture

Sources & evidence

ORD record
ord-e5e933a151a148988b45592c7aeddfbe
Source dataset
uspto-grants-2011_05
Patent number
US07947834B2

Reaction notes

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