Hydrochloric Acid → N-[(R)-1-(3'-chloro-biphenyl-4-ylmethyl)-3-methanesulfonylamino-3-oxo-propyl]-succinamic acid

HRID 1945033Notes

Reaction equation

HRID 1945033 reaction equation
C(OC(=O)[NH:7][C@H:8]([CH2:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([Cl:30])[CH:25]=2)=[CH:20][CH:19]=1)[CH2:9][C:10]([NH:12][S:13]([CH3:16])(=[O:15])=[O:14])=[O:11])(C)(C)C.Cl.[C:33]1(=[O:39])[O:38][C:36](=[O:37])[CH2:35][CH2:34]1.C(N(CC)CC)C>O1CCOCC1.C(Cl)Cl.CCOC(C)=O>[Cl:30][C:26]1[CH:25]=[C:24]([C:21]2[CH:20]=[CH:19][C:18]([CH2:17][C@@H:8]([NH:7][C:33](=[O:39])[CH2:34][CH2:35][C:36]([OH:38])=[O:37])[CH2:9][C:10]([NH:12][S:13]([CH3:16])(=[O:15])=[O:14])=[O:11])=[CH:23][CH:22]=2)[CH:29]=[CH:28][CH:27]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 7922Succinic anhydrideHCID 8471TriethylamineHCID 59607782[(R)-1-(3'-Chloro-biphenyl-4-ylmethyl)-3-methanesulfonylamino-3-oxo-propyl]-carbamic acid tert-butyl ester

Product 1

HCID 59607549N-[(R)-1-(3'-chloro-biphenyl-4-ylmethyl)-3-methanesulfonylamino-3-oxo-propyl]-succinamic acidYield 42%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

[(R)-1-(3′-Chloro-biphenyl-4-ylmethyl)-3-methanesulfonylamino-3-oxo-propyl]-carbamic acid tert-butyl ester (150 mg, 0.321 mmol) is treated with 4M HCl in dioxane. After being stirred at room temperature for 1 h, the reaction mixture is concentrated in vacuo. To this residue in DCM (2 mL) are added succinic anhydride (48.2 mg, 0.482 mmol) and triethylamine (0.112 mL, 0.803 mmol). After being stirred at room temperature for 2 h, the reaction mixture is diluted with EtOAc and washed with 1M HCl and brine. The organic layer is dried over Na2SO4 and concentrated. The residue is 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 (63 mg). HPLC retentions time=1.32 minutes (condition A); MS (m+1)=467; 1H NMR (400 Mz, DMSO-d6) δ ppm 2.22-2.29 (m, 2H), 2.32-2.54 (m, 4H), 2.77 (d, 2H, J=6.82 Hz), 3.17 (s, 3H), 4.31 (dt, 1H, J=7.33, 13.9 Hz), 7.28 (d, 2H, J=8.08 Hz), 7.38-7.43 (m, 1H), 7.48 (t, 1H, J=7.83 Hz), 7.62 (d, 3H, J=8.34 Hz), 7.70 (t, 1H, J=2.02 Hz), 7.89 (d, 1H, J=8.34 Hz), 11.70 (s, 1H), 12.04 (s, 1H).

Workup

  1. concentrationthe reaction mixture is concentrated in vacuo
  2. stirringAfter being stirred at room temperature for 2 h
  3. washwashed with 1M HCl and brine
  4. dry with materialThe organic layer is dried over Na2SO4
  5. concentrationconcentrated
  6. customThe residue is purified by reverse phase HPLC (SunFire C18, 0.1% TFA in H2O/CH3CN)

Sources & evidence

ORD record
ord-55ad6f5f54214f5f8da5a42789e80cc5
Source dataset
uspto-grants-2013_03
Patent number
US08394853B2

Reaction notes

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