Ethyl 3-phenylprop-2-enoate → Ethyl (2E)-3-(4-{[(1-aminocyclopentyl)carbonyl]amino}phenyl)acrylate

HRID 1713926Notes

Reaction equation

HRID 1713926 reaction equation
C(OC([NH:11][C:12]1([C:17]([OH:19])=O)[CH2:16][CH2:15][CH2:14][CH2:13]1)=O)C1C=CC=CC=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C([N:46]([CH2:49][CH3:50])CC)C.[C:51]([O:61][CH2:62][CH3:63])(=[O:60])[CH:52]=[CH:53][C:54]1[CH:59]=CC=[CH:56][CH:55]=1.OS(C(F)(F)F)(=O)=O.C([O-])(O)=O.[Na+]>CN(C=O)C>[NH2:11][C:12]1([C:17]([NH:46][C:49]2[CH:50]=[CH:59][C:54](/[CH:53]=[CH:52]/[C:51]([O:61][CH2:62][CH3:63])=[O:60])=[CH:55][CH:56]=2)=[O:19])[CH2:13][CH2:14][CH2:15][CH2:16]1

Participants

8

Reactant 6

HCID 7649Ethyl 3-phenylprop-2-enoateHCID 8471TriethylamineHCID 62406Trifluoromethanesulfonic acidHCID 516892Sodium BicarbonateHCID 15126351-(((Phenylmethoxy)carbonyl)amino)cyclopentanecarboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 58745796Ethyl (2E)-3-(4-{[(1-aminocyclopentyl)carbonyl]amino}phenyl)acrylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

1-{[(benzyloxy)carbonyl]amino}cyclopentanecarboxylic acid was dissolved in DMF (0.2 M). HATU (1 eq.) and triethylamine (3 eq.) were added, followed by ethyl cinnamate (0.95 eq.). The resulting mixture was stirred for 48 h at 40° C. DMF was evaporated, the resulting oil taken up in EtOAc and the solution washed with HCl (3×, 1 M), water, a solution of saturated aqueous NaHCO3 (2×) and brine. Drying over Na2SO4 and evaporation gave an orange solid, which was purified by flash chromatography on silica gel using PE/EtOAc (2.5:1, containing 1% EtOH) as the eluent. The resulting solid was immediately dissolved in DCM (0.1M) and triflic acid (5 eq.) was added dropwise at RT. After 5 min at RT, the red mixture was poured into an aqueous solution of NaHCO3. The organic phase was separated, the aqueous phase was extracted with DCM (4×) and the combined organic phases dried over Na2SO4. Evaporation gave the title compound as an off-white solid, which was used without further purification. 1H NMR (400 MHz, DMSO-d6, 300 K) δ 1.26 (t, J 7.1, 3H), 1.48-1.61 (m, 2H), 1.63-1.87 (m, 4H), 1.96-2.10 (m, 2H), 4.18 (q, J 7.1, 2H), 6.53 (d, J 16.0, 1H), 6.60-7.30 (bs, 3H), 7.59 (d, J 16.0, 1H), 7.67 (d, J 8.5, 2H), 7.76 (d, J 8.5, 2H); MS (ES+) m/z 303 (M+H)+.

Workup

  1. customDMF was evaporated
  2. washthe solution washed with HCl (3×, 1 M), water
  3. dry with materialDrying over Na2SO4 and evaporation
  4. customgave an orange solid, which
  5. customwas purified by flash chromatography on silica gel using PE/EtOAc (2.5:1, containing 1% EtOH) as the eluent
  6. dissolutionThe resulting solid was immediately dissolved in DCM (0.1M)
  7. waitAfter 5 min at RT
  8. customThe organic phase was separated
  9. extractionthe aqueous phase was extracted with DCM (4×)
  10. dry with materialthe combined organic phases dried over Na2SO4
  11. customEvaporation

Sources & evidence

ORD record
ord-cc06da5ddd26472080f6b3d7b7d9a37c
Source dataset
uspto-grants-2010_09
Patent number
US07795250B2

Reaction notes

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