Phenylmethyl (2S)-4-[(5'-{[({3-[(1-{[(1,1-dimethylethyl)oxy]carbonyl}-4-Piperidinyl)methyl]phenyl}carbonyl)amino]methyl}-2'-fluoro-3-biphenylyl)methyl]-2-methyl-1-piperazinecarboxylate → 1,1-Dimethylethyl 4-{[3-({[(6-fluoro-3'-{[(3S)-3-methyl-1-piperazinyl]methyl}-3-biphenylyl)methyl]amino}carbonyl)phenyl]methyl}-1-piperidinecarboxylate

HRID 2080321Notes

Reaction equation

HRID 2080321 reaction equation
[CH3:1][C:2]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][C:15]2[CH:16]=[C:17]([C:21]([NH:23][CH2:24][C:25]3[CH:26]=[CH:27][C:28]([F:55])=[C:29]([C:31]4[CH:36]=[CH:35][CH:34]=[C:33]([CH2:37][N:38]5[CH2:43][CH2:42][N:41](C(OCC6C=CC=CC=6)=O)[C@@H:40]([CH3:54])[CH2:39]5)[CH:32]=4)[CH:30]=3)=[O:22])[CH:18]=[CH:19][CH:20]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])[CH3:3]>CO.[Pd]>[F:55][C:28]1[C:29]([C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([CH2:37][N:38]3[CH2:43][CH2:42][NH:41][C@@H:40]([CH3:54])[CH2:39]3)[CH:32]=2)=[CH:30][C:25]([CH2:24][NH:23][C:21]([C:17]2[CH:16]=[C:15]([CH2:14][CH:11]3[CH2:10][CH2:9][N:8]([C:6]([O:5][C:2]([CH3:1])([CH3:4])[CH3:3])=[O:7])[CH2:13][CH2:12]3)[CH:20]=[CH:19][CH:18]=2)=[O:22])=[CH:26][CH:27]=1

Participants

4

Reactant 1

HCID 57730435Phenylmethyl (2S)-4-[(5'-{[({3-[(1-{[(1,1-dimethylethyl)oxy]carbonyl}-4-Piperidinyl)methyl]phenyl}carbonyl)amino]methyl}-2'-fluoro-3-biphenylyl)methyl]-2-methyl-1-piperazinecarboxylate

Product 1

HCID 577304411,1-Dimethylethyl 4-{[3-({[(6-fluoro-3'-{[(3S)-3-methyl-1-piperazinyl]methyl}-3-biphenylyl)methyl]amino}carbonyl)phenyl]methyl}-1-piperidinecarboxylateYield 35%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A solution of phenylmethyl (2S)-4-[(5′-{[({3-[(1-{[(1,1-dimethylethyl)oxy]carbonyl}-4-piperidinyl)methyl]phenyl}carbonyl)amino]methyl}-2′-fluoro-3-biphenylyl)methyl]-2-methyl-1-piperazinecarboxylate (1.5 g, 2.0 mmol) and 10% Pd/C (450 mg) in methanol (50 mL) was allowed to react with H2 at rt under atmospheric pressure for 12 hours. The solvent was removed under vacuum. The resulting residue was purified by loading onto 20 g aminopropyl SPE cartridge and eluting sequentially with DCM (3×50 mL), EtOAc (3×50 mL), and MeOH (3×50 mL). The methanol fractions were combined and evaporated to give the title compound as a pale yellow solid (60 mg, 35%). LC/MS: m/z, 615 (M+H), 1.93 min.

Workup

  1. customto react with H2 at rt under atmospheric pressure for 12 hours
  2. customThe solvent was removed under vacuum
  3. customThe resulting residue was purified
  4. washeluting sequentially with DCM (3×50 mL), EtOAc (3×50 mL), and MeOH (3×50 mL)
  5. customevaporated

Sources & evidence

ORD record
ord-3b9eba35d0174fc1b1b85cb774e553d6
Source dataset
uspto-grants-2011_04
Patent number
US07932247B2

Reaction notes

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