Ammonium Hydroxide → benzhydryl 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

HRID 708494Notes

Reaction equation

HRID 708494 reaction equation
[NH4+:1].[OH-].[C:3]([O:7][C:8]([NH:10][C:11]1[S:12][CH:13]=[C:14](/[C:16](=[N:37]/[O:38][C:39]2([C:42]([O:44][CH:45]([C:52]3[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=3)[C:46]3[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=3)=[O:43])[CH2:41][CH2:40]2)/[C:17]([NH:19][C@@H:20]2[C:23](=[O:24])[NH:22][C@@H:21]2[CH2:25][N:26]2[N:30]=[C:29]([CH2:31]OS(C)(=O)=O)[CH:28]=[N:27]2)=[O:18])[N:15]=1)=[O:9])([CH3:6])([CH3:5])[CH3:4]>CCO.C1COCC1.C(Cl)Cl>[NH2:1][CH2:31][C:29]1[CH:28]=[N:27][N:26]([CH2:25][C@@H:21]2[C@H:20]([NH:19][C:17](=[O:18])/[C:16](=[N:37]\[O:38][C:39]3([C:42]([O:44][CH:45]([C:52]4[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=4)[C:46]4[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=4)=[O:43])[CH2:41][CH2:40]3)/[C:14]3[N:15]=[C:11]([NH:10][C:8]([O:7][C:3]([CH3:5])([CH3:4])[CH3:6])=[O:9])[S:12][CH:13]=3)[C:23](=[O:24])[NH:22]2)[N:30]=1

Participants

6

Reactant 2

HCID 14923Ammonium HydroxideHCID 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 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-carboxylateYield 49%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-5 °C

Procedure

To a solution of aq. NH4OH (2 mL, 28-30% wt) in EtOH (2 mL, ratio:1) and THF (2 mL, ratio:1) was added a solution of 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 (190 mg, 0.24 mmol) in THF (1 mL) at −5° C. dropwise. After stirring at −5° C. for 1 h and rt for 12 h, the reaction mixture was diluted with 40 mL of DCM and washed with 10 mL of aq. saturated NaHCO3 (aq), 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 (120 mg, 49%). LCMS: Rt=0.87 min, m/z=716.4 (M+1) Method 2m_acidic.

Workup

  1. washwashed with 10 mL of aq. saturated NaHCO3 (aq)
  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-7c5d7f5ae29d444d84e38e97f1cbc2fd
Source dataset
uspto-grants-2015_11
Patent number
US09174978B2

Reaction notes

Loading…