Sodium Iodide → benzhydryl 1-[(Z)-[2-[[(2R,3S)-2-[[4-(6,7-dihydro-5H-pyrazolo[1,2-a][1,2,4]triazol-4-ium-6-ylsulfanylmethyl)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 chloride

HRID 708514Notes

Reaction equation

HRID 708514 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+].[Cl-:64].[SH:65][CH:66]1[CH2:73][N:69]2[CH:70]=[N:71][CH:72]=[N+:68]2[CH2:67]1>CN(C=O)C>[Cl-:64].[CH:43]([O:42][C:40]([C:37]1([O:36]/[N:35]=[C:14](/[C:12]2[N:13]=[C:9]([NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[S:10][CH:11]=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][S:65][CH:66]3[CH2:73][N:69]4[CH:70]=[N:71][CH:72]=[N+:68]4[CH2:67]3)[CH:26]=[N:25]2)=[O:16])[CH2:39][CH2:38]1)=[O:41])([C:50]1[CH:51]=[CH:52][CH:53]=[CH:54][CH:55]=1)[C:44]1[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 10796Cesium carbonateHCID 104648696,7-Dihydro-6-mercapto-5H-pyrazolo[1,2-a][1,2,4]triazolium chlorideHCID 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 118380093benzhydryl 1-[(Z)-[2-[[(2R,3S)-2-[[4-(6,7-dihydro-5H-pyrazolo[1,2-a][1,2,4]triazol-4-ium-6-ylsulfanylmethyl)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 chlorideYield 34%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Prepared in an anlogous manner to example 138, step 1 using 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 (54 mg, 0.068 mmol), sodium iodide (17.2 mg, 0.115 mmol), cesium carbonate (24.5 mg, 0.075 mmol), 6-mercapto-6,7-dihydro-5H-pyrazolo[1,2-a][1,2,4]triazol-4-ium chloride (13.4 mg, 0.075 mmol) and DMF (600 μL). The slurry was concentrated in vacuo, and the crude residue was purified via reverse phase prep HPLC (Xselect CSH, 30×100 mm, 5 μm, C18 column; ACN-water with 0.1% formic acid modifier, 60 mL/min), affording the title compound (19.7 mg, 34%) as white solid. LCMS: Rt=0.91 min, m/z=840.4 (M+) Method 2m_acidic.

Workup

  1. concentrationThe slurry was concentrated in vacuo
  2. customthe crude residue was purified via reverse phase prep HPLC (Xselect CSH, 30×100 mm, 5 μm, C18 column; ACN-water with 0.1% formic acid modifier, 60 mL/min)

Sources & evidence

ORD record
ord-70cf57075b354994a0b3254898f06af2
Source dataset
uspto-grants-2015_11
Patent number
US09174978B2

Reaction notes

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