Diisopropylethylamine → tert-butyl 2-[(Z)-[1-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-oxo-2-[[(3S,4R)-2-oxo-4-(1,2,4-triazol-1-ylmethyl)azetidin-3-yl]amino]ethylidene]amino]oxyacetate

HRID 708380Notes

Reaction equation

HRID 708380 reaction equation
[C:1]([O:5][C:6](=[O:27])[CH2:7][O:8]/[N:9]=[C:10](/[C:14]1[N:15]=[C:16]([NH:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[S:17][CH:18]=1)\[C:11]([OH:13])=O)([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[N:61]1([CH2:66][C@H:67]2[NH:70][C:69](=[O:71])[C@H:68]2[NH2:72])[CH:65]=[N:64][CH:63]=[N:62]1>C(Cl)Cl.CCOC(C)=O>[N:61]1([CH2:66][C@@H:67]2[C@H:68]([NH:72][C:11](=[O:13])/[C:10](=[N:9]\[O:8][CH2:7][C:6]([O:5][C:1]([CH3:3])([CH3:4])[CH3:2])=[O:27])/[C:14]3[N:15]=[C:16]([NH:19][C:20]([O:22][C:23]([CH3:26])([CH3:24])[CH3:25])=[O:21])[S:17][CH:18]=3)[C:69](=[O:71])[NH:70]2)[CH:65]=[N:64][CH:63]=[N:62]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 14510362(Z)-2-((2-(tert-butoxy)-2-oxoethoxy)imino)-2-(2-((tert-butoxycarbonyl)amino)thiazol-4-yl)acetic acidHCID 118390218(3S,4R)-4-((1H-1,2,4-triazol-1-yl)methyl)-3-aminoazetidin-2-one

Product 1

HCID 139298648tert-butyl 2-[(Z)-[1-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-oxo-2-[[(3S,4R)-2-oxo-4-(1,2,4-triazol-1-ylmethyl)azetidin-3-yl]amino]ethylidene]amino]oxyacetateYield 72%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (Z)-2-((2-(tert-butoxy)-2-oxoethoxy)imino)-2-(2-((tert-butoxycarbonyl)amino)thiazol-4-yl)acetic acid (108 mg, 0.269 mmol) in DCM (2.7 mL) at 0° C. was added DIPEA (141 μL, 0.808 mmol) followed by HATU (113 mg, 0.296 mmol). To the resulting solution, after 20 min, was added a solution of (3S,4R)-4-((1H-1,2,4-triazol-1-yl)methyl)-3-aminoazetidin-2-one (50 mg, 0.299 mmol) in DCM. After 1 h of stirring it was diluted with EtOAc, washed with water, brine, dried over Na2SO4 and concentrated in vacuo. The crude residue was purified via silica gel chromatography (Acetone-DCM) to afford the title compound (106 mg, 72%). LCMS: R=0.78 min, m/z=551.2 (M+1) Method 2m_acidic.

Workup

  1. washwashed with water, brine
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. customThe crude residue was purified via silica gel chromatography (Acetone-DCM)

Sources & evidence

ORD record
ord-7d59b6f98a3d445db384d60ff8212f6a
Source dataset
uspto-grants-2015_11
Patent number
US09174978B2

Reaction notes

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