Diisopropylethylamine → benzhydryl 1-[(Z)-[2-[[(2R,3S)-2-[[4-(hydroxymethyl)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 708466Notes

Reaction equation

HRID 708466 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@@H:76]([CH2:77][N:78]2[N:82]=[C:81]([CH2:83][OH:84])[CH:80]=[N:79]2)[NH:75][C:74]1=[O:85]>C(Cl)Cl.CN(C=O)C>[C:35]([O:34][C:32]([NH:31][C:28]1[S:29][CH:30]=[C:26](/[C:22](=[N:21]/[O:20][C:17]2([C:15]([O:14][CH:1]([C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=3)=[O:16])[CH2:18][CH2:19]2)/[C:23]([NH:72][C@@H:73]2[C:74](=[O:85])[NH:75][C@@H:76]2[CH2:77][N:78]2[N:82]=[C:81]([CH2:83][OH:84])[CH:80]=[N:79]2)=[O:24])[N:27]=1)=[O:33])([CH3:37])([CH3:36])[CH3:38]

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 118380161(3S,4R)-3-amino-4-((4-(hydroxymethyl)-2H-1,2,3-triazol-2-yl)methyl)azetidin-2-one

Product 1

HCID 118379587benzhydryl 1-[(Z)-[2-[[(2R,3S)-2-[[4-(hydroxymethyl)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 78.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of (Z)-2-((1-((benzhydryloxy)carbonyl)cyclopropoxy)imino)-2-(2-((tert-butoxycarbonyl)amino)thiazol-4-yl)acetic acid (2.5 g, 4.43 mmol) in DCM (78 mL) and DMF (15 ml) at 0° C. was added DIPEA (1.2 ml, 7.00 mmol), HATU (1.9 g, 5.13 mmol), and (3S,4R)-3-amino-4-((4-(hydroxymethyl)-2H-1,2,3-triazol-2-yl)methyl)azetidin-2-one (0.92 g, 4.67 mmol). After stirring at 0° C. for 1 h, the reaction mixture was diluted with DCM, washed with water, brine, dried over Na2SO4 and concentrated in vacuo. The crude residue was purified via silica gel chromatography (MeOH-DCM, 0-5%), affording the title compound (2.5 g, 75%). LCMS: R=0.98 min, m/z=717.3 (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 (MeOH-DCM, 0-5%)

Sources & evidence

ORD record
ord-af52ec9e34e14df5b3321e10f6e7dc3c
Source dataset
uspto-grants-2015_11
Patent number
US09174978B2

Reaction notes

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