Thionyl Chloride → HCID 59607864, compound

HRID 70857Notes

Reaction equation

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

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of N-[(R)-1-(3′-chloro-biphenyl-4-ylmethyl)-3-methanesulfonylamino-3-oxo-propyl]-succinamic acid (50 mg, 0.107 mmol) in n-butanol (2 mL) is added thionyl chloride (9.38 μL, 0.128 mmol). The reaction mixture is warmed to 50° C. and stirred for 1 h. After cooling to room temperature, the reaction mixture is concentrated and purified by reverse phase HPLC (SunFire C18, 0.1% TFA in H2O/CH3CN) to give N-[(R)-1-(3′-chloro-biphenyl-4-ylmethyl)-3-methanesulfonylamino-3-oxo-propyl]-succinamic acid butyl ester (32 mg). HPLC retentions time=1.56 minutes (condition A); MS (m+1)=523; 1H NMR (400 Mz, DMSO-d6) δ ppm 0.86 (t, 3H, J=7.33 Hz), 1.22-1.34 (m, 2H), 1.45-1.55 (m, 2H), 2.23-2.33 (m, 2H), 2.35-2.44 (m, 3H), 2.45-2.55 (m, 3H), 2.71-2.83 (m, 1H), 3.18 (s, 3H), 3.96 (t, 2H, J=6.57 Hz), 4.27-4.38 (m, 1H), 7.28 (d, 2H, J=8.08 Hz), 7.37-7.43 (m, 1H), 7.48 (t, 1H J=7.83 Hz), 7.62 (d, 3H, J=8.34 Hz), 7.70 (s, 1H), 7.91 (d, 1H, J=8.34 Hz), 11.71 (s, 1H).

Workup

temperatureAfter cooling to room temperature
concentrationthe reaction mixture is concentrated
custompurified by reverse phase HPLC (SunFire C18, 0.1% TFA in H2O/CH3CN)

Sources & evidence

ORD record: ord-9fe38278948146029f7d5d267b271dba
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08822534B2

Reaction notes

Loading…