1,2-Dichloroethane → 2-{4-[4-(4-Amino-phenyl)-buta-1,3-diynyl]-benzoylamino}-3-tert-butoxycarbonylamino-propionic acid methyl ester

HRID 422972Notes

Reaction equation

HRID 422972 reaction equation
CCN([CH:7]([CH3:9])[CH3:8])C(C)C.O[C@@H]1CCN([C:16]([C:18]2[CH:23]=[CH:22]C(OC(F)(F)F)=[CH:20][CH:19]=2)=[O:17])[C@H]1C(NOCC1C=CC=CC=1)=O.[CH:40]1[CH:41]=[CH:42][C:43]2[N:48](O)N=N[C:44]=2[CH:45]=1.[CH2:50](Cl)[CH2:51]Cl.[CH3:54][C:55]([O:58][C:59]([NH:61][CH2:62][C@H:63]([NH2:68])[C:64]([O:66][CH3:67])=[O:65])=[O:60])([CH3:57])[CH3:56]>CN(C=O)C.CCOC(C)=O.CCCCCC>[CH3:67][O:66][C:64](=[O:65])[CH:63]([NH:68][C:16](=[O:17])[C:18]1[CH:23]=[CH:22][C:9]([C:7]#[C:8][C:50]#[C:51][C:40]2[CH:45]=[CH:44][C:43]([NH2:48])=[CH:42][CH:41]=2)=[CH:20][CH:19]=1)[CH2:62][NH:61][C:59]([O:58][C:55]([CH3:54])([CH3:56])[CH3:57])=[O:60]

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 7021143Methyl 3-((tert-butoxycarbonyl)amino)-L-alaninateHCID 59697601((2r,3r)-3-Hydroxy-1-{[4-(trifluoromethoxy)phenyl]carbonyl}pyrrolidin-2-yl)-n-(phenylmethoxy)carboxamide

Product 1

HCID 578970282-{4-[4-(4-Amino-phenyl)-buta-1,3-diynyl]-benzoylamino}-3-tert-butoxycarbonylamino-propionic acid methyl esterYield 91%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

DIEA (10.5 ml, 60.3 mmol) was added to a stirred solution of 4-[4-(4-Amino-phenyl)-buta-1,3-diynyl]-benzoic acid (1) (5.0 g, 19.1 mmol), HOBT (2.72 g, 20.1 mmol), EDC (3.85 g, 20.1 mmol) in DMF (80 ml). After 2 min., the H-DAP(Boc)-OMe was added in one portion. After 12 hours at rt, the reaction was found complete by LCMS. The reaction was diluted with EtOAc/hexane (4:1) (500 ml). The organic phase was washed with 1N NaOH (2×80 ml), water (2×80 ml), sat. brine (80 ml), dried with Na2SO4, filtered and concentrated under reduced pressure to give crude product. The residue was filtered through a filter plug of silica eluting with EtOAc/hexane (4:1). The fractions with product were evaporated to give 8.02 g of product in 91% yield.

Workup

  1. waitAfter 12 hours at rt
  2. washThe organic phase was washed with 1N NaOH (2×80 ml), water (2×80 ml), sat. brine (80 ml)
  3. dry with materialdried with Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customto give crude product
  7. filtrationThe residue was filtered through a filter plug of silica eluting with EtOAc/hexane (4:1)
  8. customThe fractions with product were evaporated

Sources & evidence

ORD record
ord-22260034b5214ecb9440e68deadcbc83
Source dataset
uspto-grants-2012_01
Patent number
US08101640B2

Reaction notes

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