HCID 86604765, compound → HCID 67278012, compound

HRID 1714567Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([C:12]([NH:14][C@@H:15]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]3[N:29]=[C:30]([C:34](N(C)OC)=[O:35])[N:31]([CH3:33])[CH:32]=3)=[CH:24][CH:23]=2)[CH2:16][CH2:17][C:18]([OH:20])=[O:19])=[O:13])[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].[CH3:40][Mg]Br>C1COCC1>[C:34]([C:30]1[N:31]([CH3:33])[CH:32]=[C:28]([C:25]2[CH:24]=[CH:23][C:22]([CH2:21][C@H:15]([NH:14][C:12]([C:4]3[CH:5]=[CH:6][C:7]([O:8][CH:9]([CH3:11])[CH3:10])=[C:2]([Cl:1])[CH:3]=3)=[O:13])[CH2:16][CH2:17][C:18]([OH:20])=[O:19])=[CH:27][CH:26]=2)[N:29]=1)(=[O:35])[CH3:40]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of crude (4R)-4-[({3-chloro-4-[(1-methylethyl)oxy]phenyl}carbonyl)amino]-5-[4-(1-methyl-2-{[methyl(methyloxy)amino]carbonyl}-1H-imidazol-4-yl)phenyl]pentanoic acid (3.18 mmol) in anhydrous THF (16 mL) under nitrogen at 0° C. was added methylmagnesium bromide (10.6 mL, 10 equiv, 3.0 M in ether) dropwise by syringe. The reaction was stirred for 30 minutes at 0° C. and then carefully quenched with sat. aq. NH4Cl solution (10 mL), followed by 1N HCl solution (60 mL) such that the pH of the aqueous layer 5.5. The product was extracted with EtOAc (4×40 mL) and the combined organic layers were dried over MgSO4 and concentrated in vacuo to give the title compound, which was used directly in the next reaction. ESMS [M+H]+=512.4.

Workup

customcarefully quenched with sat. aq. NH4Cl solution (10 mL)
extractionThe product was extracted with EtOAc (4×40 mL)
dry with materialthe combined organic layers were dried over MgSO4
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-0a7b978aaa4848fa935a6acb6871e442
Source dataset: uspto-grants-2010_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07795448B2

Reaction notes

Loading…