HCID 59249268, compound → HCID 59249357, compound

HRID 1806695Notes

Reaction equation

HRID 1806695 reaction equation
[C:1]([O:5][C:6](=[O:40])[C@@H:7]([NH:11][C:12]([C@H:14]1[C@H:18]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[CH:20]=2)[C@:17]([C:28]2[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=2)([C:26]#[N:27])[C@H:16]([CH2:35][C:36]([CH3:39])([CH3:38])[CH3:37])[NH:15]1)=[O:13])[CH:8]([CH3:10])[CH3:9])(C)(C)C.C(OC(=O)[C@@H](NC([C@@H]1[C@@H](C2C=CC=C(Cl)C=2)[C@@](C2C=CC(Cl)=CC=2)(C#N)[C@@H](CC(C)(C)C)N1)=O)C(C)C)(C)(C)C>CO>[CH3:1][O:5][C:6](=[O:40])[C@@H:7]([NH:11][C:12]([C@@H:14]1[C@@H:18]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[CH:20]=2)[C@@:17]([C:28]2[CH:29]=[CH:30][C:31]([Cl:34])=[CH:32][CH:33]=2)([C:26]#[N:27])[C@@H:16]([CH2:35][C:36]([CH3:37])([CH3:39])[CH3:38])[NH:15]1)=[O:13])[CH:8]([CH3:10])[CH3:9]

Participants

4

Reactant 2

HCID 59249268HCID 59249268, compoundHCID 59249631HCID 59249631, compound

Product 1

HCID 59249357HCID 59249357, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Column separation from the above example (Example 10a) gave a mixture of (S)-2-{[(2R,3R,4R,5S)-3-(3-chloro-phenyl)-4-(4-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methyl-butyric acid tert-butyl ester and (S)-2-{[(2S,3S,4S,5R)-3-(3-chloro-phenyl)-4-(4-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methyl-butyric acid tert-butyl ester (45.8 mg, 15.6%). The mixture was treated with 2NH2SO4 (catalytic) in MeOH (1 mL) at 120° C. for 10 min using CEM microwave reactor to give after purification by reverse phase chromatography (20-95% of MeCN/water): (S)-2-{[(2S,3S,4S,5R)-3-(3-chloro-phenyl)-4-(4-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methyl-butyric acid methyl ester (13.5 mg, 31.8%).

Workup

  1. customColumn separation from the above example (Example 10a)
  2. customgave
  3. customto give
  4. customafter purification by reverse phase chromatography (20-95% of MeCN/water)

Sources & evidence

ORD record
ord-4c586bb1210c4468bb2a5e43eff51bca
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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