Diisopropylethylamine → benzhydryl 1-[(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]oxycyclopropane-1-carboxylate

HRID 708382Notes

Reaction equation

HRID 708382 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]([OH:25])=O)[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.[N:72]1([CH2:77][C@H:78]2[NH:81][C:80](=[O:82])[C@H:79]2[NH2:83])[CH:76]=[N:75][CH:74]=[N:73]1>C(Cl)Cl.CN(C=O)C.C(Cl)Cl.CCOC(C)=O>[N:72]1([CH2:77][C@@H:78]2[C@H:79]([NH:83][C:23](=[O:25])/[C:22](=[N:21]\[O:20][C:17]3([C:15]([O:14][CH:1]([C:8]4[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=4)[C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=4)=[O:16])[CH2:18][CH2:19]3)/[C:26]3[N:27]=[C:28]([NH:31][C:32]([O:34][C:35]([CH3:36])([CH3:37])[CH3:38])=[O:33])[S:29][CH:30]=3)[C:80](=[O:82])[NH:81]2)[CH:76]=[N:75][CH:74]=[N:73]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 118380020(Z)-2-((1-((benzhydryloxy)carbonyl)cyclopropoxy)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 140689344benzhydryl 1-[(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]oxycyclopropane-1-carboxylateYield 77%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 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) (150 mg, 0.279 mmol) in DCM:DMF (1:1, 2.8 mL) at 0° C. was added DIPEA (146 μL, 0.837 mmol) followed by HATU (127 mg, 0.335 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 (51 mg, 0.31 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 (147 mg, 77%). LCMS: Rt=0.98 min, m/z=687.1 (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-be0199a6e22741869d63e511a0567ed9
Source dataset
uspto-grants-2015_11
Patent number
US09174978B2

Reaction notes

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