Diisopropylethylamine → benzhydryl 1-[(Z)-[2-[[(2R,3S)-2-[[4-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]triazol-2-yl]methyl]-4-oxoazetidin-3-yl]amino]-1-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-oxoethylidene]amino]oxycyclopropane-1-carboxylate

HRID 708384Notes

Reaction equation

HRID 708384 reaction equation
[CH:1]([O:14][C:15]([C:17]1([O:20]/[N:21]=[C:22](/[C:26]2[N:27]=[C:28]([NH:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[S:29][CH:30]=2)\[C:23](O)=[O:24])[CH2:19][CH2:18]1)=[O:16])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.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.[NH2:72][C@@H:73]1[C:76](=[O:77])[NH:75][C@@H:74]1[CH2:78][N:79]1[N:83]=[C:82]([CH2:84][NH:85][C:86](=[O:92])[O:87][C:88]([CH3:91])([CH3:90])[CH3:89])[CH:81]=[N:80]1>C(Cl)Cl.C(Cl)Cl.CN(C=O)C>[C:88]([O:87][C:86]([NH:85][CH2:84][C:82]1[CH:81]=[N:80][N:79]([CH2:78][C@@H:74]2[C@H:73]([NH:72][C:23](=[O:24])/[C:22](=[N:21]\[O:20][C:17]3([C:15]([O:14][CH:1]([C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=4)[C:8]4[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=4)=[O:16])[CH2:19][CH2:18]3)/[C:26]3[N:27]=[C:28]([NH:31][C:32]([O:34][C:35]([CH3:38])([CH3:36])[CH3:37])=[O:33])[S:29][CH:30]=3)[C:76](=[O:77])[NH:75]2)[N:83]=1)=[O:92])([CH3:91])([CH3:89])[CH3:90]

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 118380020(Z)-2-((1-((benzhydryloxy)carbonyl)cyclopropoxy)imino)-2-(2-((tert-butoxycarbonyl)amino)thiazol-4-yl)acetic acidHCID 131733744tert-butyl((2-(((2R,3S)-3-amino-4-oxoazetidin-2-yl)methyl)-2H-1,2,3-triazol-4-yl)methyl)carbamate

Product 1

HCID 140689335benzhydryl 1-[(Z)-[2-[[(2R,3S)-2-[[4-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]triazol-2-yl]methyl]-4-oxoazetidin-3-yl]amino]-1-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-oxoethylidene]amino]oxycyclopropane-1-carboxylateYield 84.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

To a solution of (Z)-2-((1-((benzhydryloxy)carbonyl)cyclopropoxy)imino)-2-(2-((tert-butoxycarbonyl)amino)thiazol-4-yl)acetic acid (prepared according to Yamawaki et al. Bioorg. Med. Chem. Lett. 2007, 15, 6716-6732) (1.50 g, 2.79 mmol) in DCM (15 mL) at 0° C. was added DIPEA (1.22 mL, 6.98 mmol) and HATU (1.11 g, 2.93 mmol). After warming to rt, a solution of tert-butyl ((2-(((2R,3S)-3-amino-4-oxoazetidin-2-yl)methyl)-2H-1,2,3-triazol-4-yl)methyl)carbamate (827 mg, 2.79 mmol) in DCM:DMF (1.7:1, 12.7 mL). After 1 h of stirring it was diluted with DCM and washed with water, brine, dried over Na2SO4 and concentrated in vacuo. The crude residue was purified via silica gel chromatography (EtOAc-Heptane, 0-90%), to afford the title compound (1.92 g, 84%) as a purple oil. LCMS: Rt=1.08 min, m/z=816.5 (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 (EtOAc-Heptane, 0-90%)

Sources & evidence

ORD record
ord-586c6044d6fe4607a2776eead51c5c07
Source dataset
uspto-grants-2015_11
Patent number
US09174978B2

Reaction notes

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