N-(tert-butoxycarbonyl)glycine → ((2S,4R)-4-(2-aminoacetamido)-1-(2-chlorobenzylcarbamoyl)pyrrolidin-2-yl)methyl 4-ethylphenylcarbamate

HRID 655981

Reaction equation

HRID 655981 reaction equation
[CH2:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:30])[O:11][CH2:12][C@@H:13]2[CH2:17][C@@H:16]([NH2:18])[CH2:15][N:14]2[C:19](=[O:29])[NH:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[Cl:28])=[CH:5][CH:4]=1)[CH3:2].[NH:31](C(OC(C)(C)C)=O)[CH2:32][C:33](O)=[O:34].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH2:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:30])[O:11][CH2:12][C@@H:13]2[CH2:17][C@@H:16]([NH:18][C:33](=[O:34])[CH2:32][NH2:31])[CH2:15][N:14]2[C:19](=[O:29])[NH:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[Cl:28])=[CH:5][CH:4]=1)[CH3:2]

Participants

5

Reactant 3

HCID 78288N-(tert-butoxycarbonyl)glycineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59778486((2S,4R)-4-amino-1-(2-chlorobenzylcarbamoyl)pyrrolidin-2-yl)methyl 4-ethylphenylcarbamate

Product 1

HCID 25026415((2S,4R)-4-(2-aminoacetamido)-1-(2-chlorobenzylcarbamoyl)pyrrolidin-2-yl)methyl 4-ethylphenylcarbamateYield 54.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of ((2S,4R)-4-amino-1-(2-chlorobenzylcarbamoyl)pyrrolidin-2-yl)methyl 4-ethylphenylcarbamate (60 mg, 0.14 mmol) in DMF were added Boc-Gly-OH (37 mg, 0.21 mmol) and HBTU (80 mg, 0.21 mmol). The reaction mixture was stirred at rt overnight and purified on RP-HPLC using a mixture of acetonitrile and H2O. The fraction containing the product was combined and concentrated. The residue was dissolved in MeOH and 4N HCl in dioxane. The reaction mixture was stirred at rt for 1 h and concentrated to give ((2S,4R)-4-(2-aminoacetamido)-1-(2-chlorobenzylcarbamoyl)pyrrolidin-2-yl)methyl 4-ethylphenylcarbamate (37 mg, 51%). LRMS (M+H+) m/z 488.1.

Workup

  1. custompurified on RP-HPLC
  2. additiona mixture of acetonitrile and H2O
  3. additionThe fraction containing the product
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in MeOH
  6. stirringThe reaction mixture was stirred at rt for 1 h
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-d201994f44bb495cb3f625e6f9650642
Source dataset
uspto-grants-2011_12
Patent number
US08071625B2

Linked notes

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