HCID 86701375, compound → HCID 178454245, compound

HRID 1424520Notes

Reaction equation

HRID 1424520 reaction equation
[C:1]([O:5][C:6]([N:8]=[C:9]([NH:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[NH:10][CH2:11][C:12]#[CH:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:22]([O:29][N:30]1[C:36](=[O:37])[N:35]2[CH2:38][C@H:31]1[CH2:32][CH2:33][C@H:34]2[C:39](Cl)=[N:40][OH:41])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>C(Cl)Cl>[CH2:22]([O:29][N:30]1[C:36](=[O:37])[N:35]2[CH2:38][C@H:31]1[CH2:32][CH2:33][C@H:34]2[C:39]1[CH:13]=[C:12]([CH2:11][NH:10][C:9]([NH:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=[N:8][C:6]([O:5][C:1]([CH3:3])([CH3:4])[CH3:2])=[O:7])[O:41][N:40]=1)[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1

Participants

4

Reactant 2

HCID 86701375HCID 86701375, compoundHCID 178457572HCID 178457572, compound

Product 1

HCID 178454245HCID 178454245, compoundYield 27.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1-(2,3-bis(tert-butoxycarbonyl)guanidino)prop-2-yne (362 mg, 1.22 mmol) was added to the solution of (2S,5R)-6-(benzyloxy)-N-hydroxy-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbimidoyl chloride (473 mg, 1.53 mmol) in dry DCM (20 mL) at rt, followed by dropwise addition of TEA (0.16 g, 1.53 mmol). The mixture was stirred at rt for 2 hrs and then concentrated. The residue was purified by silica gel column chromatography (gradient elution 1:15 to 1:5 EtOAc/Hexanes) to give (2S,5R)-6-(benzyloxy)-2-(5-((2,3-bis(tert-butoxycarbonyl)guanidino)methyl)isoxazol-3-yl)-1,6-diaza-bicyclo[3.2.1]octan-7-one (190 mg, 22% for two steps) as a white solid. ESI-MS (EI+, m/z): 571.2 [M+H]+. 1H NMR (500 MHz, CDCl3): δ 11.49 (s, 1H), 8.86 (bs, 1H), 7.47-7.34 (m, 5H), 6.32 (s, 1H), 5.09 (d, J=11.5 Hz, 1H), 4.93 (d, J=12.0 Hz, 1H), 4.87-4.76 (m, 2H), 4.59 (d, J=7.0 Hz, 1H), 3.36 (s, 1H), 2.87-2.85 (m, 1H), 2.70 (d, J=12 Hz, 1H), 2.35-2.30 (m, 1H), 2.24-2.18 (m, 1H), 2.10-2.05 (m, 1H), 1.81-1.78 (m, 1H), 1.50 (s, 18H).

Workup

  1. concentrationconcentrated
  2. customThe residue was purified by silica gel column chromatography (gradient elution 1:15 to 1:5 EtOAc/Hexanes)

Sources & evidence

ORD record
ord-e5120716dc2945b1a98fb71e06323f10
Source dataset
uspto-grants-2015_01
Patent number
US08927724B2

Reaction notes

Loading…