Diisopropylethylamine → Biphenyl-2-ylcarbamic Acid 1-[2-(4-Aminomethylphenylcarbamoyl)ethyl]piperidin-4-yl Ester

HRID 2193570Notes

Reaction equation

HRID 2193570 reaction equation
C(OC([NH:8][CH2:9][C:10]1[CH:16]=[CH:15][C:13]([NH2:14])=[CH:12][CH:11]=1)=O)(C)(C)C.[C:17]1([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[NH:23][C:24]([O:26][CH:27]1[CH2:32][CH2:31][N:30]([CH2:33][CH2:34][C:35](O)=[O:36])[CH2:29][CH2:28]1)=[O:25].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.C(O)(C(F)(F)F)=O.C(Cl)Cl>[NH2:8][CH2:9][C:10]1[CH:11]=[CH:12][C:13]([NH:14][C:35]([CH2:34][CH2:33][N:30]2[CH2:29][CH2:28][CH:27]([O:26][C:24](=[O:25])[NH:23][C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=3[C:38]3[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=3)[CH2:32][CH2:31]2)=[O:36])=[CH:15][CH:16]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2756041tert-butyl N-[(4-aminophenyl)methyl]carbamateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 218806073-[4-(Biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]propionic Acid

Product 1

HCID 59340340Biphenyl-2-ylcarbamic Acid 1-[2-(4-Aminomethylphenylcarbamoyl)ethyl]piperidin-4-yl EsterYield 94%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 21863450Trifluoroacetic acid methylene chlorideSolvent

Conditions

Temperature
50 °C

Procedure

To a stirred solution of 4-(N-tert-butoxycarbonylaminomethyl)aniline (756 mg, 3.4 mmol), 3-[4-(biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]propionic acid (1.5 g, 4.08 mmol; prepared as described in Preparation 3) and HATU (1.55 g, 4.08 mmol) in DMF (6.8 mL), was added DIPEA (770 μL, 4.42 mmol). The reaction mixture was stirred at 50° C. overnight, and then the solvent was removed under reduced pressure. The resulting residue was dissolved in DCM (20 mL) and washed with saturated aqueous sodium bicarbonate solution (10 mL). The organic phase was then dried (magnesium sulfate) and the solvent was removed under reduced pressure. The crude product was purified by flash chromatography (5-10% MeOH/DCM) to give a solid, which was dissolved in TFA/DCM (25%, 30 mL) and stirred at room temperature for 2 hours. The solvent was then removed under reduced pressure and the crude residue was dissolved in DCM (30 mL) and washed with 1N NaOH (15 mL). The organic phase was separated, dried (magnesium sulfate), filtered and the solvent was removed under reduced pressure to give 1.5 g of the title intermediate (94% yield over 2 steps).

Workup

  1. customthe solvent was removed under reduced pressure
  2. dissolutionThe resulting residue was dissolved in DCM (20 mL)
  3. washwashed with saturated aqueous sodium bicarbonate solution (10 mL)
  4. dry with materialThe organic phase was then dried (magnesium sulfate)
  5. customthe solvent was removed under reduced pressure
  6. customThe crude product was purified by flash chromatography (5-10% MeOH/DCM)
  7. customto give a solid, which
  8. stirringstirred at room temperature for 2 hours
  9. customThe solvent was then removed under reduced pressure
  10. dissolutionthe crude residue was dissolved in DCM (30 mL)
  11. washwashed with 1N NaOH (15 mL)
  12. customThe organic phase was separated
  13. dry with materialdried (magnesium sulfate)
  14. filtrationfiltered
  15. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-a90466f5a1b144e9b2b7ad9924a852ee
Source dataset
uspto-grants-2012_12
Patent number
US08329911B2

Reaction notes

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