HCID 86604765, compound → HCID 67278012, compound

HRID 1785050Notes

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 1 N 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-9b006af1c25e4eab9109a00f18f384e4
Source dataset: uspto-grants-2009_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07504413B2

Reaction notes

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