4-Methylmorpholine → 2-[3-Cyclopropyl-2-(2-nitro-benzenesulfonylamino)-propionylamino]-3-naphthalen-2-yl-propionic acid methyl ester

HRID 720165Notes

Reaction equation

HRID 720165 reaction equation
[CH:1]1([C:4]([NH:9][S:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[N+:19]([O-:21])=[O:20])(=[O:12])=[O:11])(C)[C:5]([OH:7])=O)[CH2:3][CH2:2]1.[CH3:22][O:23][C:24](=[O:38])[C@@H:25]([NH2:37])[CH2:26][C:27]1[CH:36]=[CH:35][C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH:28]=1.[CH3:39]N1CCOCC1.ON1C2C=CC=CC=2N=N1.CN(C)CCCN=C=NCC>CN(C=O)C>[CH3:22][O:23][C:24](=[O:38])[CH:25]([NH:37][C:5](=[O:7])[CH:4]([NH:9][S:10]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[N+:19]([O-:21])=[O:20])(=[O:11])=[O:12])[CH2:1][CH:3]1[CH2:2][CH2:39]1)[CH2:26][C:27]1[CH:36]=[CH:35][C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH:28]=1

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 9291934(S)-methyl 2-amino-3-(naphthalen-2-yl)propanoateHCID 21901755Cyclopropyl-2-(2-nitro-benzenesulfonylamino)-propionic acid

Product 1

HCID 695877582-[3-Cyclopropyl-2-(2-nitro-benzenesulfonylamino)-propionylamino]-3-naphthalen-2-yl-propionic acid methyl esterYield 85.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of cyclopropyl-2-(2-nitro-benzenesulfonylamino)-propionic acid (7.74 mmol) in DMF (10 mL) are added 2-(S)-amino-3-naphthalen-2-yl-propionic acid methyl ester (3.1 g, 11.7 mmol), N-methylmorpholine (4.67 g, 46.27 mmol), 1-hydroxybenzotriazole (17.76 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (1.93 g, 10.07 mmol) consecutively. The resulting mixture is stirred for 4 hours, quenched with aqueous NH4Cl and extracted with ethyl acetate. The combined extracts are dried over Na2SO4, filtered and concentrated in vacuo. The residue is purified over silica gel (hexanes/ethyl acetate, 1:1) to afford 3.46 g (85% yield) of the desired product. 1H NMR (300 MHz, CDCl3) δ 8.04 (dd, J=7.7, 1.4 Hz, 1H), 7.42–7.68 (m, 9H), 7.24 (dd, J=8.4, 1.5 Hz, 1H), 6.94 (d, J=8.1 Hz, 1H), 6.20 (d, J=6.9 Hz, 1H), 4.84–4.96 (m, 1H), 3.98–4.07 (m, 1H), 3.71 (s, 3H), 3.29 (dd, J=14.0, 5.6 Hz, 1H), 3.14 (dd, J=14.0, 7.4 Hz, 1H), 1.62–1.72 (m, 1H), 1.23–1.42 (m, 1H), 0.02–0.40 (m, 3H), −0.14–0.02(, 2H); 13C NMR (75 MHz, CDCl3) δ 171.74, 170.45, 147.91, 134.02, 133.73, 133.61, 133.18, 132.70, 131.07, 128.55, 128.32, 127.89, 127.41, 126.54, 126.12, 125.76, 58.59, 53.56, 52.74, 38.34, 37.55, 6.86, 4.38; MS (ESMS) m/z 526.1 (M+H)+.

Workup

  1. customquenched with aqueous NH4Cl
  2. extractionextracted with ethyl acetate
  3. dry with materialThe combined extracts are dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue is purified over silica gel (hexanes/ethyl acetate, 1:1)

Sources & evidence

ORD record
ord-d47a333daf1c44329949312cf7d62c16
Source dataset
uspto-grants-2006_11
Patent number
US07132539B2

Reaction notes

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