Trifluoroacetic acid → N-[4-({(2S,5R)-5-[(R)-hydroxy(phenyl)methyl]pyrrolidin-2-yl}methyl)phenyl]-N'-(3-methoxyphenyl)urea

HRID 1947764Notes

Reaction equation

HRID 1947764 reaction equation
[NH2:1][C:2]1[CH:28]=[CH:27][C:5]([CH2:6][C@@H:7]2[CH2:11][CH2:10][C@H:9]([C@H:12]([OH:19])[C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[N:8]2C(OC(C)(C)C)=O)=[CH:4][CH:3]=1.[N:29]([C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([O:38][CH3:39])[CH:33]=1)=[C:30]=[O:31].C(O)(C(F)(F)F)=O>C(Cl)Cl>[OH:19][C@H:12]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C@@H:9]1[NH:8][C@H:7]([CH2:6][C:5]2[CH:27]=[CH:28][C:2]([NH:1][C:30]([NH:29][C:32]3[CH:37]=[CH:36][CH:35]=[C:34]([O:38][CH3:39])[CH:33]=3)=[O:31])=[CH:3][CH:4]=2)[CH2:11][CH2:10]1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 878433-Methoxyphenyl isocyanateHCID 57907643tert-Butyl (2S,5R)-2-(4-aminobenzyl)-5-((R)-hydroxy(phenyl)methyl)pyrrolidine-1-carboxylate

Product 1

HCID 57907490N-[4-({(2S,5R)-5-[(R)-hydroxy(phenyl)methyl]pyrrolidin-2-yl}methyl)phenyl]-N'-(3-methoxyphenyl)urea

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 30 mg (0.078 mmol) of tert-butyl (2S,5R)-2-(4-aminobenzyl)-5-[(R)-hydroxy(phenyl)methyl]pyrrolidine-1-carboxylate (i-13a) in CH2Cl2 (0.5 mL) was added 14 mg (0.094 mmol) of 1-isocyanato-3-methoxybenzene. The reaction mixture was stirred at ambient temperature for 2.5 h. It was then added TFA (0.4 mL) and was stirred at ambient temperature for another 3 h. After removal of the volatiles, it was purified by reverse-phase HPLC (TMC Pro-Pac C18; 10-80% 0.1% trifluoroacetic acid in acetonitrile/0.1% trifluoroacetic acid in water gradient). The pure fractions were lyophilized overnight to give the title compound as a white solid. LC/MS 432.3 (M+1).

Workup

  1. customAfter removal of the volatiles, it
  2. customwas purified by reverse-phase HPLC (TMC Pro-Pac C18; 10-80% 0.1% trifluoroacetic acid in acetonitrile/0.1% trifluoroacetic acid in water gradient)
  3. waitThe pure fractions were lyophilized overnight

Sources & evidence

ORD record
ord-0bcd15e1f70e4219a792f892b9232ce7
Source dataset
uspto-grants-2013_03
Patent number
US08399480B2

Reaction notes

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