Dimethylformamide → tert-butyl 3-[[[2-[[(2R,3S)-3-[[(2Z)-2-(1-benzhydryloxycarbonylcyclopropyl)oxyimino-2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]acetyl]amino]-4-oxoazetidin-2-yl]methyl]triazol-4-yl]methylamino]methyl]azetidine-1-carboxylate

HRID 708458Notes

Reaction equation

HRID 708458 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[S:10][CH:11]=[C:12](/[C:14](=[N:31]/[O:32][C:33]2([C:36]([O:38][CH:39]([C:46]3[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=3)[C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)=[O:37])[CH2:35][CH2:34]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]([CH:29]=O)[CH:26]=[N:25]2)=[O:16])[N:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:52][CH2:53][CH:54]1[CH2:57][N:56]([C:58]([O:60][C:61]([CH3:64])([CH3:63])[CH3:62])=[O:59])[CH2:55]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].CN(C=O)C>ClCCCl>[CH:39]([O:38][C:36]([C:33]1([O:32]/[N:31]=[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][NH:52][CH2:53][CH:54]3[CH2:57][N:56]([C:58]([O:60][C:61]([CH3:64])([CH3:63])[CH3:62])=[O:59])[CH2:55]3)[CH:26]=[N:25]2)=[O:16])[CH2:35][CH2:34]1)=[O:37])([C:46]1[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=1)[C:40]1[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 5049666Sodium triacetoxyborohydrideHCID 10679125Tert-butyl 3-(aminomethyl)azetidine-1-carboxylateHCID 118379394benzhydryl 1-[(Z)-[2-[[(2R,3S)-2-[(4-formyltriazol-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 118379848tert-butyl 3-[[[2-[[(2R,3S)-3-[[(2Z)-2-(1-benzhydryloxycarbonylcyclopropyl)oxyimino-2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]acetyl]amino]-4-oxoazetidin-2-yl]methyl]triazol-4-yl]methylamino]methyl]azetidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of benzhydryl 1-(((Z)-(1-(2-((tert-butoxycarbonyl)amino)thiazol-4-yl)-2-(((2R,3S)-2-((4-formyl-2H-1,2,3-triazol-2-yl)methyl)-4-oxoazetidin-3-yl)amino)-2-oxoethylidene)amino)oxy)cyclopropanecarboxylate (150 mg, 0.21 mmol) in DCE (4 ml) at 0° C. was added tert-butyl 3-(aminomethyl)azetidine-1-carboxylate (78 mg, 0.420 mmol), sodium triacetoxyborohydride (66.7 mg, 0.315 mmol), and DMF (0.4 mL). After stirring at rt for 3 h, the reaction mixture was quenched with saturated NaHCO3 (aq) and diluted with 10% EtOH/DCM (40 mL). The organic layer was separated, dried with Na2SO4, filtered and concentrated in vacuo. The crude residue was used as such in the following step. LCMS: Rt=0.55 min, m/z=885.5 (M+1). Method 2m_acidic.

Workup

  1. customthe reaction mixture was quenched with saturated NaHCO3 (aq)
  2. additiondiluted with 10% EtOH/DCM (40 mL)
  3. customThe organic layer was separated
  4. dry with materialdried with Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b2b6bfe85fa54a47987d468bb06865e1
Source dataset
uspto-grants-2015_11
Patent number
US09174978B2

Reaction notes

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