1,2-Dichloroethane → (2S,2S)-nicotinic acid 2-[(4-amino-benzenesulfonyl)-isobutyl-amino]-6-(2-methoxycarbonylamino-3,3-diphenyl-propionylamino)-hexyl ester

HRID 1677226Notes

Reaction equation

HRID 1677226 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][C@H:6]([N:17]([S:22]([C:25]1[CH:30]=[CH:29][C:28]([NH2:31])=[CH:27][CH:26]=1)(=[O:24])=[O:23])[CH2:18][CH:19]([CH3:21])[CH3:20])[CH2:7][O:8][C:9](=[O:16])[C:10]1[CH:15]=[CH:14][CH:13]=[N:12][CH:11]=1.C(N(CC)CC)C.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[CH3:53][O:54][C:55]([NH:57][C@@H:58]([CH:62]([C:69]1[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=1)[C:63]1[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=1)[C:59](O)=[O:60])=[O:56]>CN(C=O)C>[NH2:31][C:28]1[CH:27]=[CH:26][C:25]([S:22]([N:17]([CH2:18][CH:19]([CH3:21])[CH3:20])[C@@H:6]([CH2:5][CH2:4][CH2:3][CH2:2][NH:1][C:59](=[O:60])[C@@H:58]([NH:57][C:55]([O:54][CH3:53])=[O:56])[CH:62]([C:69]2[CH:70]=[CH:71][CH:72]=[CH:73][CH:74]=2)[C:63]2[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=2)[CH2:7][O:8][C:9](=[O:16])[C:10]2[CH:15]=[CH:14][CH:13]=[N:12][CH:11]=2)(=[O:24])=[O:23])=[CH:30][CH:29]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 10017620(S)-2-methoxycarbonylamino-3,3-diphenyl-propionic acidHCID 131726927(2S)-nicotinic acid 6-amino-2-[(4-amino-benzenesulfonyl)-isobutyl-amino]-hexyl ester

Product 1

HCID 11721810(2S,2S)-nicotinic acid 2-[(4-amino-benzenesulfonyl)-isobutyl-amino]-6-(2-methoxycarbonylamino-3,3-diphenyl-propionylamino)-hexyl esterYield 20%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The product of step B, (2S)-nicotinic acid 6-amino-2-[(4-amino-benzenesulfonyl)-isobutyl-amino]-hexyl ester (100 mg, 0.22 mmol) was dissolved in anhydrous. DMF (2 mL) and treated with 0.062 mL (0.45 mmol) of triethylamine followed by EDC (100 mg, 0.56 mmol), HOBt (75 mg, 0.56 mmol) and (2S)-2-methoxycarbonylamino-3,3-diphenyl-propionic acid (56 mg, 0.19 mmol). The mixture was stirred overnight at room temperature. The product was extracted with ethyl acetate (40 mL) and water (40 mL). The organic layer was separated and dried with Na2SO4, then evaporated to give 160 mg of crude oil. The residue was purified by flash chromatography with a mixture of eluents hexane/ethyl acetate (2/8). The title compound was obtained as a clear oil in 20% yield (25 mg).

Workup

  1. extractionThe product was extracted with ethyl acetate (40 mL) and water (40 mL)
  2. customThe organic layer was separated
  3. dry with materialdried with Na2SO4
  4. customevaporated
  5. customto give 160 mg of crude oil
  6. customThe residue was purified by flash chromatography with a mixture of eluents hexane/ethyl acetate (2/8)

Sources & evidence

ORD record
ord-d9c929645fc747cdae24c8144beaad00
Source dataset
uspto-grants-2011_08
Patent number
US08008297B2

Reaction notes

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