Sodium Iodide → benzhydryl 1-[(Z)-[2-[[(2R,3S)-2-[[4-[[4-[(2-methylpropan-2-yl)oxycarbonylamino]piperidin-1-yl]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 708512Notes

Reaction equation

HRID 708512 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[S:10][CH:11]=[C:12](/[C:14](=[N:35]/[O:36][C:37]2([C:40]([O:42][CH:43]([C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=3)[C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)=[O:41])[CH2:39][CH2:38]2)/[C:15]([NH:17][C@@H:18]2[C:21](=[O:22])[NH:20][C@@H:19]2[CH2:23][N:24]2[N:28]=[C:27]([CH2:29]OS(C)(=O)=O)[CH:26]=[N:25]2)=[O:16])[N:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[I-].[Na+].C(=O)([O-])[O-].[Cs+].[Cs+].[NH:64]1[CH2:69][CH2:68][CH:67]([NH:70][C:71](=[O:77])[O:72][C:73]([CH3:76])([CH3:75])[CH3:74])[CH2:66][CH2:65]1>CN(C=O)C.CCOC(C)=O.[Li+].[Cl-]>[C:73]([O:72][C:71]([NH:70][CH:67]1[CH2:66][CH2:65][N:64]([CH2:29][C:27]2[CH:26]=[N:25][N:24]([CH2:23][C@@H:19]3[C@H:18]([NH:17][C:15](=[O:16])/[C:14](=[N:35]\[O:36][C:37]4([C:40]([O:42][CH:43]([C:50]5[CH:51]=[CH:52][CH:53]=[CH:54][CH:55]=5)[C:44]5[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=5)=[O:41])[CH2:38][CH2:39]4)/[C:12]4[N:13]=[C:9]([NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[S:10][CH:11]=4)[C:21](=[O:22])[NH:20]3)[N:28]=2)[CH2:69][CH2:68]1)=[O:77])([CH3:74])([CH3:76])[CH3:75]

Participants

8

Reactant 4

HCID 5238Sodium IodideHCID 10796Cesium carbonateHCID 7238334-(N-Boc-amino)piperidineHCID 118379964benzhydryl 1-[(Z)-[1-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-[[(2R,3S)-2-[[4-(methylsulfonyloxymethyl)triazol-2-yl]methyl]-4-oxoazetidin-3-yl]amino]-2-oxoethylidene]amino]oxycyclopropane-1-carboxylate

Product 1

HCID 118380119benzhydryl 1-[(Z)-[2-[[(2R,3S)-2-[[4-[[4-[(2-methylpropan-2-yl)oxycarbonylamino]piperidin-1-yl]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 73%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 433294Lithium ChlorideSolvent

Procedure

Benzhydryl 1-(((Z)-(1-(2-((tert-butoxycarbonyl)amino)thiazol-4-yl)-2-(((2R,3S)-2-((4-(((methylsulfonyl)oxy)methyl)-2H-1,2,3-triazol-2-yl)methyl)-4-oxoazetidin-3-yl)amino)-2-oxoethylidene)amino)oxy)cyclopropanecarboxylate (64 mg, 0.081 mmol) and sodium iodide (18.1 mg, 0.121 mmol) were stirred in DMF (700 μL) for 14 h, whereupon cesium carbonate (33.4 mg, 0.103 mmol) and tert-butyl piperidin-4-ylcarbamate (17.7 mg, 0.089 mmol) were added. After 3 h of additional stirring the mixture was diluted with EtOAc and LiCl (5% aq) solution. The aqueous layer was extracted with EtOAc (2×) and the combined organic layers were washed with LiCl (5% aq) solution, brine, dried over Na2SO4 and concentrated in vacuo. The crude residue was purified via silica gel chromatography (1-8% MeOH-DCM), affording the title compound (52.6 mg, 73%) as an off-white solid. LCMS: Rt=0.98 min, m/z=899.7 (M+1) Method 2m_acidic.

Workup

  1. additionwere added
  2. extractionThe aqueous layer was extracted with EtOAc (2×)
  3. washthe combined organic layers were washed with LiCl (5% aq) solution, brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe crude residue was purified via silica gel chromatography (1-8% MeOH-DCM)

Sources & evidence

ORD record
ord-0e020de629da4dd1a28845858dde625e
Source dataset
uspto-grants-2015_11
Patent number
US09174978B2

Reaction notes

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