5-Aminopentan-1-ol → Biphenyl-2-ylcarbamic Acid 1-[2-(5-Oxopentylcarbamoyl)ethyl]piperidin-4-yl Ester

HRID 252885

Reaction equation

HRID 252885 reaction equation
[C:1]1([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8]([O:10][CH:11]1[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][C:19]([OH:21])=O)[CH2:13][CH2:12]1)=[O:9].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][OH:58].CCN(C(C)C)C(C)C>C(Cl)Cl.CS(C)=O>[O:58]=[CH:57][CH2:56][CH2:55][CH2:54][CH2:53][NH:52][C:19]([CH2:18][CH2:17][N:14]1[CH2:13][CH2:12][CH:11]([O:10][C:8](=[O:9])[NH:7][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=2[C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH2:16][CH2:15]1)=[O:21]

Participants

7

Reactant 4

HCID 756345-Aminopentan-1-olHCID 81531Diisopropylethylamine2×HCID 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 86607677Biphenyl-2-ylcarbamic Acid 1-[2-(5-Oxopentylcarbamoyl)ethyl]piperidin-4-yl EsterYield 80.1%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 3-[4-(biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]propionic acid (5 g, 13.5 mmol; prepared as described in Preparation 10), HATU (10.3 g, 27 mmol), 5-amino-1-pentanol (1.67 g, 16.2 mmol) and DIPEA (7.04 mL, 40.5 mmol) in 100 mL of DCM was stirred at room temperature for 1 hour. The reaction mixture was then washed with brine (100 mL), water (100 mL), dried over magnesium sulfate, filtered and concentrated. The residue was dissolved in DCM (100 mL) and cooled down to −5° C. in an ice/brine bath. DIPEA (7.04 mL, 40.5 mmol) and DMSO (10 mL) were added to the solution, followed by sulfur trioxide pyridine complex (6.45 g, 40.5 mmol). The reaction mixture was stirred at 0° C. for 2 hours and then washed with water (100 mL) and brine (2×100 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated to yield 4.88 g of the title intermediate (80% yield) as a semi-solid.

Workup

  1. washThe reaction mixture was then washed with brine (100 mL), water (100 mL)
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in DCM (100 mL)
  6. temperaturecooled down to −5° C. in an ice/brine bath
  7. stirringThe reaction mixture was stirred at 0° C. for 2 hours
  8. washwashed with water (100 mL) and brine (2×100 mL)
  9. dry with materialThe organic layer was dried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-6cb9ed3551134cc39c3a4d67d50d845e
Source dataset
uspto-grants-2011_01
Patent number
US07868175B2

Linked notes

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