1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → N-(cyclopropylmethyl)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-(1-phenylprop-2-en-1-yl)pent-4-enamide

HRID 1392083Notes

Reaction equation

HRID 1392083 reaction equation
[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[C@@H:12]([CH2:16][CH:17]=[CH2:18])[C:13]([OH:15])=O.CCN=C=NCCCN(C)C.Cl.[CH:31]1([CH2:34][NH:35][CH:36]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[CH:37]=[CH2:38])[CH2:33][CH2:32]1>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH:31]1([CH2:34][N:35]([CH:36]([C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=2)[CH:37]=[CH2:38])[C:13](=[O:15])[CH:12]([N:3]2[C:4](=[O:11])[C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[C:2]2=[O:1])[CH2:16][CH:17]=[CH2:18])[CH2:33][CH2:32]1

Participants

6

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 11139382HCID 11139382, compoundHCID 58691176N-(cyclopropylmethyl)-1-phenylprop-2-en-1-amine

Product 1

HCID 58691201N-(cyclopropylmethyl)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-(1-phenylprop-2-en-1-yl)pent-4-enamideYield 76.3%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent4×

Conditions

Temperature
-20 °C

Procedure

To a solution of (2S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)pent-4-enoic acid (4b) (166 mg) in DCM (1 mL) at −20° C. under N2 was added a mixture of EDAC.HCl (156 mg) and DMAP (3 mg) in DCM (1 mL) portionwise. This mixture stirred for ten min. before N-(cyclopropylmethyl)-1-phenylprop-2-en-1-amine (4a) (127 mg) in DCM (0.5 mL) was added dropwise. The reaction mixture was stirred for 1 h at −20° C. and 3 h at RT, then diluted with DCM (50 mL) and washed with 0.2 N HCl, saturated NaHCO3, brine, dried (Na2SO4), filtered, and evaporated. The crude product was purified via flash chromatography (5% then 10% EtOAc/hexanes) to give the desired product (214 mg, 76%). 1H NMR (300 MHz) The NMR of this compound in both CDCl3 and DMSO-d6 (with elavated temperatures) was complex, thus limiting interpretation. MS APCI, m/z=415 (M+1). LC/MS 2.86 min., Method A.

Workup

  1. additionwas added dropwise
  2. washwashed with 0.2 N HCl, saturated NaHCO3, brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. customevaporated
  6. customThe crude product was purified via flash chromatography (5%

Sources & evidence

ORD record
ord-45dab1a8c19a477da54721865eaf3785
Source dataset
uspto-grants-2008_03
Patent number
US07342007B2

Reaction notes

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