Diisopropylethylamine → benzhydryl 1-[(Z)-[2-[[(2R,3S)-2-[[4-[[4-[(2-methylpropan-2-yl)oxycarbonylamino]butanoylamino]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 708495Notes

Reaction equation

HRID 708495 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][CH2:11][C:12]([OH:14])=O)=[O:7])([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.[NH2:48][CH2:49][C:50]1[CH:54]=[N:53][N:52]([CH2:55][C@@H:56]2[C@H:59]([NH:60][C:61](=[O:97])/[C:62](=[N:76]\[O:77][C:78]3([C:81]([O:83][CH:84]([C:91]4[CH:96]=[CH:95][CH:94]=[CH:93][CH:92]=4)[C:85]4[CH:90]=[CH:89][CH:88]=[CH:87][CH:86]=4)=[O:82])[CH2:80][CH2:79]3)/[C:63]3[N:64]=[C:65]([NH:68][C:69]([O:71][C:72]([CH3:75])([CH3:74])[CH3:73])=[O:70])[S:66][CH:67]=3)[C:58](=[O:98])[NH:57]2)[N:51]=1>C(Cl)Cl>[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][CH2:11][C:12]([NH:48][CH2:49][C:50]1[CH:54]=[N:53][N:52]([CH2:55][C@@H:56]2[C@H:59]([NH:60][C:61](=[O:97])/[C:62](=[N:76]\[O:77][C:78]3([C:81]([O:83][CH:84]([C:91]4[CH:96]=[CH:95][CH:94]=[CH:93][CH:92]=4)[C:85]4[CH:90]=[CH:89][CH:88]=[CH:87][CH:86]=4)=[O:82])[CH2:80][CH2:79]3)/[C:63]3[N:64]=[C:65]([NH:68][C:69]([O:71][C:72]([CH3:73])([CH3:75])[CH3:74])=[O:70])[S:66][CH:67]=3)[C:58](=[O:98])[NH:57]2)[N:51]=1)=[O:14])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2948944-(((Tert-butoxy)carbonyl)amino)butanoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 118379984benzhydryl 1-[(Z)-[2-[[(2R,3S)-2-[[4-(aminomethyl)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

Product 1

HCID 118379448benzhydryl 1-[(Z)-[2-[[(2R,3S)-2-[[4-[[4-[(2-methylpropan-2-yl)oxycarbonylamino]butanoylamino]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 46.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 4-((tert-butoxycarbonyl)amino)butanoic acid (30.7 mg, 0.15 mmol) in DCM (2 mL) at 0° C. was added DIPEA (35 μL, 0.20 mmol) and HATU (65 mg, 0.17 mmol). After 10 min, benzhydryl 1-(((Z)-(2-(((2R,3S)-2-((4-(aminomethyl)-2H-1,2,3-triazol-2-yl)methyl)-4-oxoazetidin-3-yl)amino)-1-(2-((tert-butoxycarbonyl)amino)thiazol-4-yl)-2-oxoethylidene)amino)oxy)cyclopropanecarboxylate (90 mg, 0.10 mmol) was added. After stirring at 0° C. for 1 h, the reaction mixture was diluted with DCM (40 mL), washed with 2M aq. Na2CO3 (20 mL), brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified via silica gel chromatography (MeOH-DCM, 5-10%) to afford the title compound (42 mg, 46%). LCMS: Rt=1.07 min, m/z=901.5 (M+1) Method 2m_acidic.

Workup

  1. washwashed with 2M aq. Na2CO3 (20 mL), brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified via silica gel chromatography (MeOH-DCM, 5-10%)

Sources & evidence

ORD record
ord-769cf7b0db01461bbee64cd2fc6d0938
Source dataset
uspto-grants-2015_11
Patent number
US09174978B2

Reaction notes

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