m-Chloroperbenzoic acid → (1-{2-[5-(7-{2-[1-(2-Methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-5-oxo-5H-5lambda4-dibenzothiophen-3-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester

HRID 1185779Notes

Reaction equation

HRID 1185779 reaction equation
[CH3:1][O:2][C:3](=[O:55])[NH:4][CH:5]([C:9]([N:11]1[CH2:15][CH2:14][CH2:13][CH:12]1[C:16]1[NH:17][C:18]([C:21]2[CH:22]=[CH:23][C:24]3[C:28]4[CH:29]=[CH:30][C:31]([C:33]5[NH:34][C:35]([CH:38]6[CH2:42][CH2:41][CH2:40][N:39]6[C:43](=[O:53])[CH:44]([NH:48][C:49]([O:51][CH3:52])=[O:50])[CH:45]([CH3:47])[CH3:46])=[N:36][CH:37]=5)=[CH:32][C:27]=4[S:26][C:25]=3[CH:54]=2)=[CH:19][N:20]=1)=[O:10])[CH:6]([CH3:8])[CH3:7].C1C=C(Cl)C=C(C(OO)=[O:64])C=1>C(Cl)Cl.C(OCC)(=O)C>[CH3:1][O:2][C:3](=[O:55])[NH:4][CH:5]([C:9]([N:11]1[CH2:15][CH2:14][CH2:13][CH:12]1[C:16]1[NH:17][C:18]([C:21]2[CH:22]=[CH:23][C:24]3[C:28]4[CH:29]=[CH:30][C:31]([C:33]5[NH:34][C:35]([CH:38]6[CH2:42][CH2:41][CH2:40][N:39]6[C:43](=[O:53])[CH:44]([NH:48][C:49]([O:51][CH3:52])=[O:50])[CH:45]([CH3:47])[CH3:46])=[N:36][CH:37]=5)=[CH:32][C:27]=4[S:26](=[O:64])[C:25]=3[CH:54]=2)=[CH:19][N:20]=1)=[O:10])[CH:6]([CH3:7])[CH3:8]

Participants

5

Reactant 2

HCID 70297m-Chloroperbenzoic acidHCID 66621070(1-{2-[5-(7-{2-[1-(2-Methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-dibenzothiophen-3-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester

Product 1

HCID 66620340(1-{2-[5-(7-{2-[1-(2-Methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-5-oxo-5H-5lambda4-dibenzothiophen-3-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl esterYield 33%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-40 °C

Procedure

(1-{2-[5-(7-{2-[1-(2-Methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-dibenzothiophen-3-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (0.0041 mmol., 4 mg) was dissolved in 1 mL DCM and cooled to −40° C. mCPBA (0.4 mg, 0.9 eq.) was added. The reaction mixture was stirred at −40° C. for 2 hours and warmed up to 0° C. over 2 hours, then warmed up to room temperature overnight. The reaction mixture was diluted with ethyl acetate and washed with saturated sodium bicarbonate solution. The organic layer was dried (MgSO4), concentrated and purified by preparative reverse phase HPLC (GEMINI, 5 to 100% ACN/H2O+0.1% TFA). Product was lyophilized to give a yellow powder (1-{2-[5-(7-{2-[1-(2-Methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-5-oxo-5H-5λ4-dibenzothiophen-3-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (Example DD) (0.6 mg).

Workup

  1. additionwas added
  2. temperaturewarmed up to 0° C. over 2 hours
  3. temperaturewarmed up to room temperature overnight
  4. washwashed with saturated sodium bicarbonate solution
  5. dry with materialThe organic layer was dried (MgSO4)
  6. concentrationconcentrated
  7. custompurified by preparative reverse phase HPLC (GEMINI, 5 to 100% ACN/H2O+0.1% TFA)

Sources & evidence

ORD record
ord-52778bdcb6bf49f4bfd873bb6542170d
Source dataset
uspto-grants-2014_03
Patent number
US08669234B2

Reaction notes

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