Diisopropylethylamine → tert-butyl 2-methyl-2-[(Z)-[2-[[(2R,3S)-2-[[5-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]tetrazol-2-yl]methyl]-4-oxoazetidin-3-yl]amino]-1-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-oxoethylidene]amino]oxypropanoate

HRID 708349Notes

Reaction equation

HRID 708349 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.[NH2:63][C@@H:64]1[C:67](=[O:68])[NH:66][C@@H:65]1[CH2:69][N:70]1[N:74]=[N:73][C:72]([CH2:75][NH:76][C:77](=[O:83])[O:78][C:79]([CH3:82])([CH3:81])[CH3:80])=[N:71]1>C(Cl)Cl.CN(C=O)C>[C:79]([O:78][C:77]([NH:76][CH2:75][C:72]1[N:73]=[N:74][N:70]([CH2:69][C@@H:65]2[C@H:64]([NH:63][C:13](=[O:15])/[C:12](=[N:11]\[O:10][C:7]([CH3:8])([CH3:9])[C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:29])/[C:16]3[N:17]=[C:18]([NH:21][C:22]([O:24][C:25]([CH3:26])([CH3:27])[CH3:28])=[O:23])[S:19][CH:20]=3)[C:67](=[O:68])[NH:66]2)[N:71]=1)=[O:83])([CH3:82])([CH3:80])[CH3:81]

Participants

6

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 131733721tert-butyl ((2-(((2R,3S)-3-amino-4-oxoazetidin-2-yl)methyl)-2H-tetrazol-5-yl)methyl)carbamate

Product 1

HCID 140689322tert-butyl 2-methyl-2-[(Z)-[2-[[(2R,3S)-2-[[5-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]tetrazol-2-yl]methyl]-4-oxoazetidin-3-yl]amino]-1-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-oxoethylidene]amino]oxypropanoateYield 70%

Reagents, catalysts & solvents 1

HCID 22350042dichloromethane N,N-dimethylformamideSolvent2×

Procedure

To a solution of (Z)-2-(((1-(tert-butoxy)-2-methyl-1-oxopropan-2-yl)oxy)imino)-2-(2-((tert-butoxycarbonyl)amino)thiazol-4-yl)acetic acid (938 mg, 2.18 mmol) in DCM:DMF (5:1, 8.5 mL) at 0° C. was added DIPEA (953 μL, 5.46 mmol) followed by HATU (830 mg, 2.18 mmol). To the resulting solution was added a solution of tert-butyl ((2-(((2R,3S)-3-amino-4-oxoazetidin-2-yl)methyl)-2H-tetrazol-5-yl)methyl)carbamate (541 mg, 1.82 mmol) in DCM:DMF (5:1, 8.5 mL). The solution was stirred at rt for 1 h then concentrated in vacuo, dissolved in EtOAc and washed with brine. The aqueous layer was extracted with EtOAc and the combined organic layers were washed with brine (3×), dried over Na2SO4 and concentrated in vacuo. The crude residue was purified via silica gel chromatography (Acetone-DCM, 30-50%), affording the title compound (897 mg, 70%) as a purple solid. LCMS: Rt=1.01 min, m/z=709.3 (M+1) Method 2m_acidic.

Workup

  1. concentrationthen concentrated in vacuo
  2. dissolutiondissolved in EtOAc
  3. washwashed with brine
  4. extractionThe aqueous layer was extracted with EtOAc
  5. washthe combined organic layers were washed with brine (3×)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe crude residue was purified via silica gel chromatography (Acetone-DCM, 30-50%)

Sources & evidence

ORD record
ord-dbcc5a9f81574663bb157946d130f5c4
Source dataset
uspto-grants-2015_11
Patent number
US09174978B2

Reaction notes

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