1,2-Dichloroethane → {1-Cyclohexyl-2-[4-methanesulfonyl-6-(1-phenyl-ethylcarbamoyl)-hexahydro-pyrrolo[3,2-b]pyrrol-1-yl]-2-oxo-ethyl}-carbamic acid tert-butyl ester

HRID 446970Notes

Reaction equation

HRID 446970 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]([CH:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1)[C:10]([N:12]1[CH:19]2[CH:15]([N:16]([S:23]([CH3:26])(=[O:25])=[O:24])[CH2:17][CH:18]2[C:20]([OH:22])=O)[CH2:14][CH2:13]1)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:33][C@@H:34]([NH2:41])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>C(Cl)Cl>[C:1]([O:5][C:6](=[O:7])[NH:8][CH:9]([CH:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1)[C:10]([N:12]1[CH2:13][CH2:14][CH:15]2[N:16]([S:23]([CH3:26])(=[O:24])=[O:25])[CH2:17][CH:18]([C:20](=[O:22])[NH:41][CH:34]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[CH3:33])[CH:19]12)=[O:11])([CH3:2])([CH3:4])[CH3:3]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 6431891-Phenethylamine, (+)-HCID 672816954-(2-tert-Butoxycarbonylamino-2-cyclohexyl-acetyl)-1-methanesulfonyl-octahydro-pyrrolo[3,2-b]pyrrole-3-carboxylic acid

Product 1

HCID 67282347{1-Cyclohexyl-2-[4-methanesulfonyl-6-(1-phenyl-ethylcarbamoyl)-hexahydro-pyrrolo[3,2-b]pyrrol-1-yl]-2-oxo-ethyl}-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 29 (115 mg, 0.24 mmol) in DCM (6 mL) was cooled to 0° C. and treated with (R)-(+)-α-methylbenzylamine (36 μL, 0.28 mmol), EDC (71 mg, 0.37 mmol), and HOBT (51 mg, 0.37 mmol). To this solution was then added DIPEA (0.2 mL, 1.2 mmol). The reaction mixture was allowed to warm to ambient temperature. After 16 h, the solution was diluted with DCM, washed with 1M HCl, dried over anhydrous Na2SO4, filtered and concentrated to give crude 30 as an off-white foam. The crude residue was diluted with ACN/H2O containing 0.1% HOAc and purified by reverse-phase HPLC (2″ Dynamax® C18, 10% ACN/H2O to 100% ACN over 30 min). The product-containing fractions were combined and concentrated, diluted with EtOAc and washed successively with saturated NaHCO3 and brine. The combined aqueous layers were back-extracted with DCM and the combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated to afford 30 as an off-white foam. Mass spectrum, m/z [577.6] (M+H)+.

Workup

  1. washwashed with 1M HCl
  2. dry with materialdried over anhydrous Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-de9dad1bdd36497fbd506a1ee40f37aa
Source dataset
uspto-grants-2013_07
Patent number
US08481495B2

Reaction notes

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