Diisopropylethylamine → tert-butyl 2-methyl-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]oxypropanoate

HRID 708364Notes

Reaction equation

HRID 708364 reaction equation
[C:1]([O:5][C:6](=[O:29])[C:7]([O:10]/[N:11]=[C:12](/[C:16]1[N:17]=[C:18]([NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[S:19][CH:20]=1)\[C:13]([OH:15])=O)([CH3:9])[CH3:8])([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:63]1([CH2:68][C@H:69]2[NH:72][C:71](=[O:73])[C@H:70]2[NH2:74])[CH:67]=[N:66][CH:65]=[N:64]1>C(Cl)Cl.CN(C=O)C.O.C(Cl)Cl>[N:63]1([CH2:68][C@@H:69]2[C@H:70]([NH:74][C:13](=[O:15])/[C:12](=[N:11]\[O:10][C:7]([CH3:8])([CH3:9])[C:6]([O:5][C:1]([CH3:3])([CH3:4])[CH3:2])=[O:29])/[C:16]3[N:17]=[C:18]([NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[S:19][CH:20]=3)[C:71](=[O:73])[NH:72]2)[CH:67]=[N:66][CH:65]=[N:64]1

Participants

8

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 189632922-(((1-(tert-Butoxy)-2-methyl-1-oxopropan-2-yl)oxy)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 118379995tert-butyl 2-methyl-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]oxypropanoateYield 65%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×HCID 21908982Water methylene chlorideSolvent

Procedure

To a slurry of (Z)-2-(((1-(tert-butoxy)-2-methyl-1-oxopropan-2-yl)oxy)imino)-2-(2-((tert-butoxycarbonyl)amino)thiazol-4-yl)acetic acid (81 mg, 0.19 mmol) in DCM (800 μL) at 0° C. was added DIPEA (88 μL, 0.504 mmol) followed by HATU (72 mg, 0.190 mmol). A few drops of DMF were added to homogenize the mixture. To the resulting solution was added a solution of (3S,4R)-4-((1H-1,2,4-triazol-1-yl)methyl)-3-aminoazetidin-2-one (21 mg, 0.126 mmol) in DCM (1 mL). After 1.5 h of stirring it was diluted with water/DCM and the layers separated. The aqueous layer was extracted with DCM and the combined organic layers were dried over Na2SO4 and concentrated in vacuo. The crude residue was purified via silica gel chromatography (Acetone-DCM) to afford the title compound (47 mg, 65%). LCMS: Rt=0.88 min, m/z=579.3 (M+1) Method 2m_acidic.

Workup

  1. stirringAfter 1.5 h of stirring it
  2. customthe layers separated
  3. extractionThe aqueous layer was extracted with DCM
  4. dry with materialthe combined organic layers were dried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe crude residue was purified via silica gel chromatography (Acetone-DCM)

Sources & evidence

ORD record
ord-1af08a0323a441eaa62c41a94620eaaa
Source dataset
uspto-grants-2015_11
Patent number
US09174978B2

Reaction notes

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