Cyclopentanone → ethyl (2Z)-3-(5-chloro-6-([(3R)-1-cyclopentyl-3-pyrrolidinyl]amino)-3-pyridinyl)-2-fluoroacrylate

HRID 226439Notes

Reaction equation

HRID 226439 reaction equation
Cl.Cl.[Cl:3][C:4]1[CH:5]=[C:6](/[CH:16]=[C:17](\[F:23])/[C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH:7]=[N:8][C:9]=1[NH:10][C@@H:11]1[CH2:15][CH2:14][NH:13][CH2:12]1.[C:24]1(=O)[CH2:28][CH2:27][CH2:26][CH2:25]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])([O-])=O.[K+].[K+]>C(Cl)(Cl)Cl.CCN(CC)CC>[Cl:3][C:4]1[CH:5]=[C:6](/[CH:16]=[C:17](\[F:23])/[C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH:7]=[N:8][C:9]=1[NH:10][C@@H:11]1[CH2:15][CH2:14][N:13]([CH:24]2[CH2:28][CH2:27][CH2:26][CH2:25]2)[CH2:12]1

Participants

7

Reactant 4

HCID 8452CyclopentanoneHCID 11430Potassium CarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 86603743ethyl (2Z)-3-{5-chloro-6-[(3R)-3-pyrrolidinylamino]-3-pyridinyl}-2-fluoroacrylate dihydrochloride

Product 1

HCID 86603745ethyl (2Z)-3-(5-chloro-6-([(3R)-1-cyclopentyl-3-pyrrolidinyl]amino)-3-pyridinyl)-2-fluoroacrylateYield 99.9%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
27.5 °C

Procedure

A mixture of ethyl (2Z)-3-{5-chloro-6-[(3R)-3-pyrrolidinylamino]-3-pyridinyl}-2-fluoroacrylate dihydrochloride (720 mg), cyclopentanone (188 mg), sodium triacetoxyborohydride (1.18 g) and Et3N (0.52 ml) in CHCl3 (20 ml) was stirred at 25-30° C. for 15 hours. The 10% K2CO3 solution (2 ml) was added to a reaction mixture and stirred at ambient temperature for 30 minutes and extracted with CH2Cl2 and washed with brine and dried over MgSO4. The solvent was evaporated in vacuo and the residue was chromatographed on silicagel eluting with CHCl3-MeOH (96:4). The eluted fractions containing the desired product were collected and evaporated in vacuo to give ethyl (2Z)-3-(5-chloro-6-([(3R)-1-cyclopentyl-3-pyrrolidinyl]amino)-3-pyridinyl)-2-fluoroacrylate (710 mg).

Workup

  1. stirringstirred at ambient temperature for 30 minutes
  2. extractionextracted with CH2Cl2
  3. washwashed with brine
  4. dry with materialdried over MgSO4
  5. customThe solvent was evaporated in vacuo
  6. customthe residue was chromatographed on silicagel
  7. washeluting with CHCl3-MeOH (96:4)
  8. additionThe eluted fractions containing the desired product
  9. customwere collected
  10. customevaporated in vacuo

Sources & evidence

ORD record
ord-20966383d321434b86b5035f2eb83624
Source dataset
uspto-grants-2009_07
Patent number
US07557127B2

Reaction notes

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