Diisopropylethylamine → Ethyl (2E)-3-{5-chloro-6-[(3R)-3-pyrrolidinylamino]-3-pyridyl}acrylate dihydrochloride

HRID 2376007Notes

Reaction equation

HRID 2376007 reaction equation
C([N:8]1[CH2:12][CH2:11][C@@H:10]([NH:13][C:14]2[N:19]=[CH:18][C:17](/[CH:20]=[CH:21]/[C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:16][C:15]=2[Cl:27])[CH2:9]1)C1C=CC=CC=1.[Cl:28]C(OC(Cl)C)=O.C(N(CC)C(C)C)(C)C>C1(C)C=CC=CC=1>[ClH:27].[ClH:28].[Cl:27][C:15]1[CH:16]=[C:17](/[CH:20]=[CH:21]/[C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH:18]=[N:19][C:14]=1[NH:13][C@@H:10]1[CH2:11][CH2:12][NH:8][CH2:9]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 5213051-Chloroethyl chloroformateHCID 86603634ethyl (2E)-3-(6-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}-5-chloro-3-pyridyl)acrylate

Product 1

HCID 86603632Ethyl (2E)-3-{5-chloro-6-[(3R)-3-pyrrolidinylamino]-3-pyridyl}acrylate dihydrochlorideYield 299%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of ethyl (2E)-3-(6-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}-5-chloro-3-pyridyl)acrylate (770 mg) in toluene (14 ml) was added 1-chloroethyl chloroformate (713 mg) at 23° C. and stirred at the same temperature for 1 hour. N,N-Diisopropylethylamine (0.348 ml) was added to the mixture, and the solution was stirred at 23° C. for 15 minutes. After it was concentrated under reduced pressure, the resulting residue was dissolved in EtOH (15 ml). The mixture was stirred at 65° C. for 30 minutes, and concentrated under reduced pressure. The residue was dissolved into EtOH (15 ml), and mixed with 2N-hydrogen chloride in EtOH solution (2 ml). The mixture was stirred at 86° C. for 5 hours. After it was concentrated under reduced pressure, the resulting residue was triturated with IPE (15 ml). Ethyl (2E)-3-{5-chloro-6-[(3R)-3-pyrrolidinylamino]-3-pyridyl}acrylate dihydrochloride (1.1 g) was obtained as brown syrup.

Workup

  1. stirringthe solution was stirred at 23° C. for 15 minutes
  2. concentrationAfter it was concentrated under reduced pressure
  3. dissolutionthe resulting residue was dissolved in EtOH (15 ml)
  4. stirringThe mixture was stirred at 65° C. for 30 minutes
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe residue was dissolved into EtOH (15 ml)
  7. additionmixed with 2N-hydrogen chloride in EtOH solution (2 ml)
  8. stirringThe mixture was stirred at 86° C. for 5 hours
  9. concentrationAfter it was concentrated under reduced pressure
  10. customthe resulting residue was triturated with IPE (15 ml)

Sources & evidence

ORD record
ord-fa0d88237ea547b8b3ad88792a2cb1ab
Source dataset
uspto-grants-2008_12
Patent number
US07465731B2

Reaction notes

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