Hydrogen Peroxide → HCID 68768583, compound

HRID 2265272Notes

Reaction equation

HRID 2265272 reaction equation
[CH3:1][O:2][C:3](=[O:38])[CH:4]([NH:15][C:16](=[O:37])[C:17]1[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:18]=1[NH:24][S:25]([C:28]1[C:33]2=[N:34][S:35][N:36]=[C:32]2[CH:31]=[CH:30][CH:29]=1)(=[O:27])=[O:26])[C:5]([C:7]1[CH:12]=[CH:11][C:10]([Cl:13])=[C:9]([Cl:14])[CH:8]=1)=[O:6].C([BH-](C(CC)C)C(CC)C)(CC)C.[Li+].[OH-].[Na+].OO>C1COCC1.CCO.O>[CH3:1][O:2][C:3](=[O:38])[CH:4]([NH:15][C:16](=[O:37])[C:17]1[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:18]=1[NH:24][S:25]([C:28]1[C:33]2=[N:34][S:35][N:36]=[C:32]2[CH:31]=[CH:30][CH:29]=1)(=[O:27])=[O:26])[CH:5]([C:7]1[CH:12]=[CH:11][C:10]([Cl:13])=[C:9]([Cl:14])[CH:8]=1)[OH:6]

Participants

8

Reactant 4

HCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 3611392Lithium tri-s-butylborohydrideHCID 68768681HCID 68768681, compound

Product 1

HCID 68768583HCID 68768583, compound

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of 2-[2-(benzo[1,2,5]thiadiazole-4-sulfonylamino)-4-chloro-benzoylamino]-3-(3,4-dichloro-phenyl)-3-oxo-propionic acid methyl ester (35 mg, 0.057 mmol) in THF (2 mL) was cooled to −78° C. and lithium tri-sec-butylborohydride (L-Selectride; 1 M in THF, 86 μL, 0.086 mmol) was added. The mixture was stirred at −78° C. for 1 h and water (0.1 mL), EtOH (0.1 mL), 15% NaOH (0.1 mL), and 30% H2O2 (0.1 mL) were added and the solution was warmed to rt. The mixture was diluted with satd. aq. Na2S2O3 and water and extracted with EtOAc (3×). The combined organic layers were washed with brine, dried (MgSO4), and concentrated. The crude product was purified by reverse phase HPLC to provide 2-[2-(benzo[1,2,5]thiadiazole-4-sulfonylamino)-4-chloro-benzoylamino]-3-(3,4-dichloro-phenyl)-3-hydroxy-propionic acid methyl ester as a single diastereomer (20 mg, 57%). The methyl ester was hydrolyzed as in EXAMPLE 2, Part E, to provide the title compound (73%). HPLC: RT=9.51 min. MS (ESI−): mass calcd. for C22H15Cl3N4O5S2, 601.87; m/z found, 599/601 [M−H]−. 1H NMR (400 MHz, CDCl3): 11.31 (s, 1H), 8.34 (dd, J=7.0, 0.6, 1H), 8.19 (dd, J=8.8, 0.6, 1H), 7.71 (dd, J=8.8, 7.1, 1H), 7.64 (d, J=1.9, 1H), 7.43 (d, J=1.7, 1H), 7.36 (d, J=8.3, 1H), 7.23 (d, J=8.5, 1H), 7.18 (dd, J=8.3, 1.8, 1H), 7.01 (d, J=7.3, 1H), 6.86 (dd, J=8.4, 1.9, 1H), 5.37 (d, J=3.7, 1H), 5.10 (dd, J=7.3, 3.9, 1H).

Workup

  1. temperaturethe solution was warmed to rt
  2. additionThe mixture was diluted with satd
  3. extractionaq. Na2S2O3 and water and extracted with EtOAc (3×)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. customThe crude product was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-d1a6319260904832af0497c1a9e05239
Source dataset
uspto-grants-2010_12
Patent number
US07855292B2

Reaction notes

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