Diisopropylethylamine → tert-butyl 2-methyl-2-[(Z)-[1-[5-[(2-methylpropan-2-yl)oxycarbonylamino]-1,2,4-thiadiazol-3-yl]-2-oxo-2-[[(3S,4R)-2-oxo-4-(1,2,4-triazol-1-ylmethyl)azetidin-3-yl]amino]ethylidene]amino]oxypropanoate

HRID 708378Notes

Reaction equation

HRID 708378 reaction equation
[C:1]([O:5][C:6](=[O:29])[C:7]([O:10]/[N:11]=[C:12](/[C:16]1[N:20]=[C:19]([NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[S:18][N:17]=1)\[C:13](O)=[O:14])([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.C(Cl)Cl>[N:63]1([CH2:68][C@@H:69]2[C@H:70]([NH:74][C:13](=[O:14])/[C:12](=[N:11]\[O:10][C:7]([CH3:8])([CH3:9])[C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:29])/[C:16]3[N:20]=[C:19]([NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:26])[CH3:27])=[O:23])[S:18][N:17]=3)[C:71](=[O:73])[NH:72]2)[CH:67]=[N:66][CH:65]=[N:64]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 21904557(2Z)-2-[2-methyl-1-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]oxyimino-2-[5-[(2-methylpropan-2-yl)oxycarbonylamino]-1,2,4-thiadiazol-3-yl]acetic acidHCID 118390218(3S,4R)-4-((1H-1,2,4-triazol-1-yl)methyl)-3-aminoazetidin-2-one

Product 1

HCID 118379457tert-butyl 2-methyl-2-[(Z)-[1-[5-[(2-methylpropan-2-yl)oxycarbonylamino]-1,2,4-thiadiazol-3-yl]-2-oxo-2-[[(3S,4R)-2-oxo-4-(1,2,4-triazol-1-ylmethyl)azetidin-3-yl]amino]ethylidene]amino]oxypropanoateYield 58%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

To a slurry of (Z)-2-(((1-(tert-butoxy)-2-methyl-1-oxopropan-2-yl)oxy)imino)-2-(5-((tert-butoxycarbonyl)amino)-1,2,4-thiadiazol-3-yl)acetic acid (129 mg, 0.299 mmol) in DCM:DMF (1:1, 3 mL) at 0° C. was added DIPEA (157 μL, 0.897 mmol) followed by HATU (136 mg, 0.359 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 2 h of stirring it was concentrated in vacuo and taken up in 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 (100 mg, 58%). LCMS: Rt=0.82 min, m/z=580.2 (M+1) Method 2m_acidic.

Workup

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

Sources & evidence

ORD record
ord-b72e4662d0ed4f8b9c8d45088d35edd9
Source dataset
uspto-grants-2015_11
Patent number
US09174978B2

Reaction notes

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