Ammonia → HCID 22470419, compound

HRID 394992Notes

Reaction equation

HRID 394992 reaction equation
N.O.O[N:4]1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[Cl:25][C:26]1[CH:27]=[N:28][C:29]2[C:34]([C:35]=1[CH2:36][CH2:37][CH2:38][C:39]1([C:56]([OH:58])=O)[CH2:44][CH2:43][N:42]([CH2:45][CH2:46][O:47][C:48]3[CH:53]=[C:52]([F:54])[CH:51]=[C:50]([F:55])[CH:49]=3)[CH2:41][CH2:40]1)=[CH:33][C:32]([O:59][CH3:60])=[CH:31][CH:30]=2>O1CCOCC1.ClCCl.O.C(N(CC)CC)C>[Cl:25][C:26]1[CH:27]=[N:28][C:29]2[C:34]([C:35]=1[CH2:36][CH2:37][CH2:38][C:39]1([C:56]([NH2:4])=[O:58])[CH2:44][CH2:43][N:42]([CH2:45][CH2:46][O:47][C:48]3[CH:53]=[C:52]([F:54])[CH:51]=[C:50]([F:55])[CH:49]=3)[CH2:41][CH2:40]1)=[CH:33][C:32]([O:59][CH3:60])=[CH:31][CH:30]=2

Participants

9

Reactant 4

HCID 222AmmoniaHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 22468509HCID 22468509, compound

Product 1

HCID 22470419HCID 22470419, compoundYield 75.5%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
20 °C

Procedure

13.4 cm3 of a 0.5N solution of aqueous ammonia in dioxane, 0.229 g of 1-hydroxybenzotriazole hydrate, 0.64 g of 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride and 0.46 cm3 of triethylamine were added, with stirring and under an inert atmosphere, to a mixture of 0.69 g of 4-[3-(3-chloro-6-methoxyquinolin-4-yl)propyl]-1-[2-(3,5-difluorophenoxy)ethyl]piperidine-4-carboxylic acid in 30 cm3 of dichloromethane. The suspension obtained was stirred for 17 hours at a temperature in the region of 20° C. The reaction mixture was diluted with 50 cm3 of water, stirred and the phases were separated by settling. The aqueous phase was extracted with twice 25 cm3 of dichloromethane and the organic extracts were combined, washed with 25 cm3 of saturated aqueous sodium chloride solution, dried over magnesium sulfate and then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The solid was taken up in 20 cm3 of diisopropyl ether, stirred and then filtered. 0.52 g of 4-[3-(3-chloro-6-methoxyquinolin-4-yl)propyl]-1-[2-(3,5-difluorophenoxy)ethyl]piperidine-4-carboxamide was obtained.

Workup

  1. customThe suspension obtained
  2. stirringstirred
  3. customthe phases were separated
  4. extractionThe aqueous phase was extracted with twice 25 cm3 of dichloromethane
  5. washwashed with 25 cm3 of saturated aqueous sodium chloride solution
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C
  8. stirringstirred
  9. filtrationfiltered

Sources & evidence

ORD record
ord-adfbc90825d14d0488ddc1caded04f85
Source dataset
uspto-grants-2003_08
Patent number
US06603005B2

Reaction notes

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