Hydrochloric Acid → (R,E)-methyl 4-(2-(5-(1,2-dithiolan-3-yl)pentanamido)ethylamino)-4-oxobut-2-enoate

HRID 869794

Reaction equation

HRID 869794 reaction equation
Cl.[NH2:2][CH2:3][CH2:4][NH:5][C:6](=[O:13])/[CH:7]=[CH:8]/[C:9]([O:11][CH3:12])=[O:10].[CH2:14]1[C@@H:18]([CH2:19][CH2:20][CH2:21][CH2:22][C:23](O)=[O:24])[S:17][S:16][CH2:15]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CC#N.CCOC(C)=O>[S:16]1[CH2:15][CH2:14][C@@H:18]([CH2:19][CH2:20][CH2:21][CH2:22][C:23]([NH:2][CH2:3][CH2:4][NH:5][C:6](=[O:13])/[CH:7]=[CH:8]/[C:9]([O:11][CH3:12])=[O:10])=[O:24])[S:17]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 6112Lipoic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86655426(E)-methyl 4-(2-aminoethylamino)-4-oxobut-2-enoate

Product 1

HCID 87351952(R,E)-methyl 4-(2-(5-(1,2-dithiolan-3-yl)pentanamido)ethylamino)-4-oxobut-2-enoateYield 64.6%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

The HCl salt of (E)-methyl 4-(2-aminoethylamino)-4-oxobut-2-enoate (0.515 mmol) was taken up in 10 mL of CH3CN along with R-lipoic acid (TCI, 106 mg, 0.515 mmol), HATU (215 mg, 0.567 mmol) and DIEA (270 μL, 1.55 mmol). The resulting reaction mixture was stirred at room temperature for 18 h and diluted with EtOAc. The organic layer was washed with brine, dried (Na2SO4) and concentrated under reduced pressure. Purification by silica gel chromatography (95% CH2Cl2, 5% MeOH) afforded 120 mg of (R,E)-methyl 4-(2-(5-(1,2-dithiolan-3-yl)pentanamido)ethylamino)-4-oxobut-2-enoate. MS (EI) calcd for C15H24N2O4S: 360.12. found 361 (M+1).

Workup

  1. customThe resulting reaction mixture
  2. washThe organic layer was washed with brine
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated under reduced pressure
  5. customPurification by silica gel chromatography (95% CH2Cl2, 5% MeOH)

Sources & evidence

ORD record
ord-d53a65a2298c46f9be9146130daec9c1
Source dataset
uspto-grants-2015_03
Patent number
US08969354B2

Linked notes

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