1,2-Dibromoethane → 2-[3-Cyclopropylmethyl-4-(2-nitro-benzene-sulfonyl)-2-oxo-piperazin-1-yl]-3-naphthalen-2-yl-propionic acid methyl ester

HRID 720166Notes

Reaction equation

HRID 720166 reaction equation
[CH3:1][O:2][C:3](=[O:37])[CH:4]([NH:16][C:17](=[O:36])[CH:18]([NH:23][S:24]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[N+:33]([O-:35])=[O:34])(=[O:26])=[O:25])[CH2:19][CH:20]1[CH2:22][CH2:21]1)[CH2:5][C:6]1[CH:15]=[CH:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]=1.Br[CH2:39][CH2:40]Br.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH3:1][O:2][C:3](=[O:37])[CH:4]([N:16]1[CH2:40][CH2:39][N:23]([S:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[N+:33]([O-:35])=[O:34])(=[O:25])=[O:26])[CH:18]([CH2:19][CH:20]2[CH2:21][CH2:22]2)[C:17]1=[O:36])[CH2:5][C:6]1[CH:15]=[CH:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]=1

Participants

5

Reactant 3

HCID 78391,2-DibromoethaneHCID 11430Potassium CarbonateHCID 695877582-[3-Cyclopropyl-2-(2-nitro-benzenesulfonylamino)-propionylamino]-3-naphthalen-2-yl-propionic acid methyl ester

Product 1

HCID 695880642-[3-Cyclopropylmethyl-4-(2-nitro-benzene-sulfonyl)-2-oxo-piperazin-1-yl]-3-naphthalen-2-yl-propionic acid methyl esterYield 98%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of 2-[3-cyclopropyl-2-(2-nitro-benzenesulfonylamino)-propionylamino]-3-naphthalen-2-yl-propionic acid methyl ester, 12, (3.46 g, 6.59 mmol) and 1,2-dibromoethane (12.38 g, 65.9 mmol) in DMF (40 mL) is added potassium carbonate (9.10 g, 65.8 mmol). The reaction mixture is stirred for 15 hours at 65° C., cooled and quenched with aqueous NH4Cl solution. The mixture is then extracted several times with EtOAc and the combined extracts dried over Na2SO4 and concentrated in vacuo. The resulting residue is purified over silica gel (hexanes/EtOAc, 1:2) to afford 3.57 g (98% yield) of the desired product. 1H NMR (300 MHz, CD3OD) δ 8.01–8.08 (m, 1H), 7.58–7.84 (m, 7H), 7.43–7.52 (m, 2H), 7.35 (dd, J=8.4 Hz, 1H), 5.38 (dd, J=11.7, 4.8 Hz, 1H), 4.33–4.44 (m, 1H), 3.76–3.88 (m, 1H), 3.69 (s, 3H), 3.21–3.66 (m, 4H), 2.99–3.14 (m, 1H), 1.40–1.53 (m, 1H), 1.02–1.16 (m, 1H), −0.14–−0.02 (m, 3H), −0.34–−0.20 (m, 2H); MS (ESMS) m/z 552.2 (M+H)+.

Workup

  1. temperaturecooled
  2. customquenched with aqueous NH4Cl solution
  3. extractionThe mixture is then extracted several times with EtOAc
  4. dry with materialthe combined extracts dried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue is purified over silica gel (hexanes/EtOAc, 1:2)

Sources & evidence

ORD record
ord-382ee30e434a403d8ab0419b23c3701e
Source dataset
uspto-grants-2006_11
Patent number
US07132539B2

Reaction notes

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