Sodium Hydroxide → HCID 70133158, compound

HRID 1107989Notes

Reaction equation

HRID 1107989 reaction equation
CCN=C=NCCCN(C)C.C1C=N[C:15]2[N:18](O)[N:19]=NC=2C=1.CC1C=C(C)C2C(=C([O:34][CH2:35][C:36]3[C:37](Cl)=[C:38](S(N4CCC[C@H]4C(NCCCCN)=O)(=O)=O)[CH:39]=[CH:40][C:41]=3[Cl:42])C=CC=2)N=1.C1(N)C(F)=C(F)C(F)=C(N)C=1F.Cl.Cl.[OH-:74].[Na+]>CN(C)C=O.C(N(CC)CC)C.O>[ClH:42].[NH2:19][N:18]=[CH:15][C:39]1[CH:40]=[CH:41][C:36]([C:35]([OH:34])=[O:74])=[CH:37][CH:38]=1

Participants

9

Reactant 5

HCID 14798Sodium HydroxideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 149026Tetrafluoro-m-phenylenediamine dihydrochlorideHCID 181649HOAtHCID 21968596HCID 21968596, compound

Product 1

HCID 70133158HCID 70133158, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8471TriethylamineSolvent

Procedure

A solution of 0.34 g (1.69.10-3 mol) of 4-(aminoiminomethyl)benzoic acid hydrochloride in 5 ml of dimethylformamide (DMF) is prepared and 0.46 g (1.69.10-3 mol) of EDCI and 0.32 g (1.69.10-3 mol) of HOAT are added. The mixture is stirred for 30 minutes at room temperature. The solution obtained is then added dropwise to a solution of 1 g (1.53.10-3 mol) of 1-[[3-[(2,4-dimethylquinolin-8-yl)oxymethyl]-2,4-dichlorophenyl]sulfonyl]-N-[4-aminobutyl]-2(S)-pyrrolidinecarboxamide (in the form of the dihydrochloride) in 5 ml of DMF and 0.46 g (4.6.10-3 mol) of triethylamine. The reaction mixture is stirred for 4 hours at room temperature and then poured into iced water. 1 N NaOH solution is added slowly to bring the pH to 8 and the mixture is extracted several times with dichloromethane. The combined organic phases are washed with water, dried over sodium sulfate and then concentrated under reduced pressure. The crude product is purified by chromatography a first time on NH2 -grafted silica gel using a dichloromethane/methanol mixture (98/2; v/v) as the eluent, and a second time on C18-grafted silica gel (type RP18) using a mixture of dichloromethane and 0.2 N HCl gas in methanol (98/2; v/v) as the eluent. After removal of the solvents under reduced pressure, the product is dissolved in 5 ml of distilled water and the solution is lyophilized to give 150 mg of the expected product in the form of a pale yellow solid (yield=13%).

Workup

  1. customThe solution obtained
  2. stirringThe reaction mixture is stirred for 4 hours at room temperature
  3. extractionthe mixture is extracted several times with dichloromethane
  4. washThe combined organic phases are washed with water
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product is purified by chromatography a first time on NH2 -grafted silica gel using a dichloromethane/methanol mixture (98/2; v/v) as the eluent
  8. additiona mixture of dichloromethane and 0.2 N HCl gas in methanol (98/2; v/v) as the eluent
  9. customAfter removal of the solvents under reduced pressure
  10. dissolutionthe product is dissolved in 5 ml of distilled water

Sources & evidence

ORD record
ord-4713d319973649ae9e0122226445f4ec
Source dataset
uspto-grants-2000_05
Patent number
US06063791

Reaction notes

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