Benzene → tert-butyl 2-[({(2R,3S)-2-hydroxy-3-[((2S)-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxoimidazolidin-1-yl}butanoyl)amino]-4-phenylbutyl}amino)methyl]pyrrolidine-1-carboxylate

HRID 216291Notes

Reaction equation

HRID 216291 reaction equation
[NH2:1][CH2:2][C@@H:3]([OH:32])[C@@H:4]([NH:12][C:13](=[O:31])[C@@H:14]([N:18]1[CH2:22][CH2:21][N:20]([CH2:23][C:24]2[N:25]=[C:26]([CH3:29])[S:27][CH:28]=2)[C:19]1=[O:30])[CH:15]([CH3:17])[CH3:16])[CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.C1C=CC=CC=1.[O:39]([C:44]([N:46]1[CH2:52][CH2:51][CH2:50][C@H:47]1[CH:48]=O)=[O:45])[C:40]([CH3:43])([CH3:42])[CH3:41].[BH4-].[Na+]>C(O)C>[OH:32][C@@H:3]([C@@H:4]([NH:12][C:13](=[O:31])[C@@H:14]([N:18]1[CH2:22][CH2:21][N:20]([CH2:23][C:24]2[N:25]=[C:26]([CH3:29])[S:27][CH:28]=2)[C:19]1=[O:30])[CH:15]([CH3:17])[CH3:16])[CH2:5][C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1)[CH2:2][NH:1][CH2:48][CH:47]1[CH2:50][CH2:51][CH2:52][N:46]1[C:44]([O:39][C:40]([CH3:41])([CH3:43])[CH3:42])=[O:45]

Participants

6

Reactant 4

HCID 241BenzeneHCID 2734674tert-butyl (2S)-2-formylpyrrolidine-1-carboxylateHCID 4311764Sodium borohydrideHCID 66891621(2S)-N-[(1S,2R)-3-amino-1-benzyl-2-hydroxypropyl]-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxoimidazolidin-1-yl}butanamide

Product 1

HCID 66891972tert-butyl 2-[({(2R,3S)-2-hydroxy-3-[((2S)-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxoimidazolidin-1-yl}butanoyl)amino]-4-phenylbutyl}amino)methyl]pyrrolidine-1-carboxylateYield 103%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
70 °C

Procedure

A solution of the product of Example 274C (59 mg) in ethanol:benzene (1 mL, 1:1) was treated with N-t-butoxylcarbonyl-(L)-prolinal (26 mg, 1 equivalent), stirred at 70° C. for 1 hour, cooled at 25° C., treated with NaBH4 (14 mg, 3 equivalents) at 25° C. and stirred for 16 hours. The mixture was quenched with saturated NH4Cl and partitioned between water and ethyl acetate. The organic layer was separated, dried over MgSO4, filtered and concentrated to give 85 mg of the crude title compound.

Workup

  1. temperaturecooled at 25° C.
  2. stirringstirred for 16 hours
  3. customThe mixture was quenched with saturated NH4Cl
  4. custompartitioned between water and ethyl acetate
  5. customThe organic layer was separated
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-1f8324259554487484ee94bb8f406dc8
Source dataset
uspto-grants-2012_06
Patent number
US08193227B2

Reaction notes

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