1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → benzyl ((1R)-1-{[methyl(1-phenylprop-2-en-1-yl)amino]carbonyl}but-3-en-1-yl)carbamate

HRID 1392077Notes

Reaction equation

HRID 1392077 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@H:12]([CH2:16][CH:17]=[CH2:18])[C:13]([OH:15])=O)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN=C=NCCCN(C)C.Cl.C(OC(=O)N[C@H]1C[CH:43]=[CH:42][C@@H:41]([C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)[N:40](C)[C:39]1=O)(C)(C)C>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH3:39][N:40]([CH:41]([C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)[CH:42]=[CH2:43])[C:13]([C@H:12]([NH:11][C:9](=[O:10])[O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[CH2:16][CH:17]=[CH2:18])=[O:15]

Participants

6

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10243780(R)-2-(((Benzyloxy)carbonyl)amino)pent-4-enoic acidHCID 58691177tert-butyl[(3S,7S)-1-methyl-2-oxo-7-phenyl-2,3,4,7-tetrahydro-1H-azepin-3-yl]carbamate

Product 1

HCID 58691199benzyl ((1R)-1-{[methyl(1-phenylprop-2-en-1-yl)amino]carbonyl}but-3-en-1-yl)carbamateYield 133.8%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent4×

Conditions

Temperature
-20 °C

Procedure

To a solution of (2R)-2-{[(benzyloxy)carbonyl]amino}pent-4-enoic acid (3a) (1.1 g) in DCM (5 mL) at −20° C. under N2 was added a mixture of EDAC.HCl (1.02 g) and DMAP (12 mg) in DCM (8 mL) portionwise. Methyl(1-phenylprop-2-en-1-yl)amine (1d) (650 mg) in DCM (3 mL) was then added dropwise to the reaction mixture. The reaction mixture was stirred for 1.5 h at −20° C. and 4 h at RT, then diluted with DCM (100 mL) and washed with 0.2 N HCl, saturated NaHCO3, brine, dried (Na2SO4), filtered, and evaporated. The crude product was purified via flash chromatography (20% EtOAc/hexanes) to give the desired product as a viscous oil (1.04 g, 63%). 1H NMR (300 MHz, CDCl3) δ 2.38-2.47 (m, 1H), 2.50-2.59 (m, 1H), 2.66-2.82 (m, 3H-diastereomer/rotamer mixture), 4.77-4.80 (m, 1H), 5.08-5.17 (m, 4H), 5.22-5.48 (m, 2H), 5.69-5.82 (m, 2H), 6.03-6.14 (m, 1H), 6.39-6.43 (m, 1H), 7.25-7.35 (m, 10H). MS APCI, m/z=379 (M+1). LC/MS 2.72 min., Method A.

Workup

  1. washwashed with 0.2 N HCl, saturated NaHCO3, brine
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. customevaporated
  5. customThe crude product was purified via flash chromatography (20% EtOAc/hexanes)

Sources & evidence

ORD record
ord-8ed93d1a6dc843298cc65d37cfe23d1d
Source dataset
uspto-grants-2008_03
Patent number
US07342007B2

Reaction notes

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