Sodium Carbonate → 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

HRID 2080320Notes

Reaction equation

HRID 2080320 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]([CH:21]=[CH:22][CH:23]=2)C(O)=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])[CH3:3].[NH2:24][CH2:25][C:26]1[CH:27]=[CH:28][C:29]([F:56])=[C:30]([C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([CH2:38][N:39]3[CH2:44][CH2:43][N:42]([C:45]([O:47][CH2:48][C:49]4[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=4)=[O:46])[C@@H:41]([CH3:55])[CH2:40]3)[CH:33]=2)[CH:31]=1.CCN(C(C)C)C(C)C.CN([C:69]([O:73]N1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.CCOC(C)=O>[CH3:4][C:2]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([CH2:14][C:15]2[CH:16]=[C:17]([C:69]([NH:24][CH2:25][C:26]3[CH:27]=[CH:28][C:29]([F:56])=[C:30]([C:32]4[CH:37]=[CH:36][CH:35]=[C:34]([CH2:38][N:39]5[CH2:44][CH2:43][N:42]([C:45]([O:47][CH2:48][C:49]6[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=6)=[O:46])[C@@H:41]([CH3:55])[CH2:40]5)[CH:33]=4)[CH:31]=3)=[O:73])[CH:21]=[CH:22][CH:23]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:1])[CH3:3]

Participants

9

Reactant 6

HCID 10340Sodium CarbonateHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 450739593-((1-(tert-Butoxycarbonyl)piperidin-4-yl)methyl)benzoic acidHCID 57730446Phenylmethyl (2S)-4-{[5'-(aminomethyl)-2'-fluoro-3-biphenylyl]methyl}-2-methyl-1-piperazinecarboxylate

Product 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

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-[(1-{[(1,1-dimethylethyl)oxy]carbonyl}-4-piperidinyl)methyl]benzoic acid (108 mg, 0.34 mmol) in dry DMF (2 mL) was added phenylmethyl (2S)-4-{[5′-(aminomethyl)-2′-fluoro-3-biphenylyl]methyl}-2-methyl-1-piperazinecarboxylate (150 mg, 0.334 mmol), DIPEA (0.1 mL, 0.7 mmol), HATU (142 mg, 0.37 mmol) and HOBt (150 mg, 1.1 mmol). The reaction mixture was stirred at room temperature for 2 h, followed by addition of saturated aq. Na2CO3 (1 mL) and EtOAc (5 mL). The organic layer was separated, dried over Na2SO4, and filtered. The filtrate was concentrated and the residue was purified on a 5 g amminopropyl SPE cartridge, eluting with DCM (3×5 mL), EtOAc (3×5 mL), and MeOH (3×5 mL). The product was recovered after evaporation of the DCM fractions (130 mg, 80%). LC/MS: m/z, 749 (M+H), 2.32 min.

Workup

  1. customThe organic layer was separated
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated
  5. customthe residue was purified on a 5 g amminopropyl SPE cartridge
  6. washeluting with DCM (3×5 mL), EtOAc (3×5 mL), and MeOH (3×5 mL)
  7. customThe product was recovered
  8. customafter evaporation of the DCM fractions (130 mg, 80%)
  9. customm/z, 749 (M+H), 2.32 min.

Sources & evidence

ORD record
ord-7a5429ec95944e8ba1c5bf91301869ee
Source dataset
uspto-grants-2011_04
Patent number
US07932247B2

Reaction notes

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