2-((tert-butoxycarbonyl)amino)ethyl 1H-imidazole-1-carboxylate → benzhydryl 1-[(Z)-[2-[[(2R,3S)-2-[[4-[[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethoxycarbonylamino]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 708508Notes

Reaction equation

HRID 708508 reaction equation
[NH2:1][CH2:2][C:3]1[CH:7]=[N:6][N:5]([CH2:8][C@@H:9]2[C@H:12]([NH:13][C:14](=[O:50])/[C:15](=[N:29]\[O:30][C:31]3([C:34]([O:36][CH:37]([C:44]4[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=4)[C:38]4[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=4)=[O:35])[CH2:33][CH2:32]3)/[C:16]3[N:17]=[C:18]([NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[S:19][CH:20]=3)[C:11](=[O:51])[NH:10]2)[N:4]=1.N1([C:57]([O:59][CH2:60][CH2:61][NH:62][C:63]([O:65][C:66]([CH3:69])([CH3:68])[CH3:67])=[O:64])=[O:58])C=CN=C1>C(Cl)Cl>[C:25]([O:24][C:22]([NH:21][C:18]1[S:19][CH:20]=[C:16](/[C:15](=[N:29]/[O:30][C:31]2([C:34]([O:36][CH:37]([C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)[C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)=[O:35])[CH2:33][CH2:32]2)/[C:14]([NH:13][C@@H:12]2[C:11](=[O:51])[NH:10][C@@H:9]2[CH2:8][N:5]2[N:4]=[C:3]([CH2:2][NH:1][C:57](=[O:58])[O:59][CH2:60][CH2:61][NH:62][C:63](=[O:64])[O:65][C:66]([CH3:67])([CH3:68])[CH3:69])[CH:7]=[N:6]2)=[O:50])[N:17]=1)=[O:23])([CH3:27])([CH3:26])[CH3:28]

Participants

4

Reactant 2

HCID 1183796332-((tert-butoxycarbonyl)amino)ethyl 1H-imidazole-1-carboxylate2×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 118379906benzhydryl 1-[(Z)-[2-[[(2R,3S)-2-[[4-[[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethoxycarbonylamino]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 56%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 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, 0.13 mmol) in DCM (2 mL) at 0° C. was added a solution of 2-((tert-butoxycarbonyl)amino)ethyl 1H-imidazole-1-carboxylate (0.59 ml, 0.19 mmol) in DCM (0.6 mL). After stirring at rt for 12 h, another 3 equiv 2-((tert-butoxycarbonyl)amino)ethyl 1H-imidazole-1-carboxylate (1.18 ml, 0.38 mmol) was added. After stirring at rt for additional 60 h, the reaction mixture was partitioned between DCM (40 mL) and water (20 mL). The organic layer was dried with Na2SO4, filtered and concentrated in vacuo. The crude residue was purified via silica gel chromatography (MeOH-DCM, 0-5%) to afford the title compound (64 mg, 56%). LCMS: Rt=1.09 min, m/z=903.5 (M+1) Method 2m_acidic.

Workup

  1. stirringAfter stirring at rt for additional 60 h
  2. customthe reaction mixture was partitioned between DCM (40 mL) and water (20 mL)
  3. dry with materialThe organic layer was dried with Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude residue was purified via silica gel chromatography (MeOH-DCM, 0-5%)

Sources & evidence

ORD record
ord-b005234494654d888d92b573163bfb21
Source dataset
uspto-grants-2015_11
Patent number
US09174978B2

Reaction notes

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