Dimethyl Sulfoxide → Biphenyl-2-ylcarbamic Acid 1-[2-(4-Formylphenylcarbamoyl)ethyl]piperidin-4-yl Ester

HRID 1948182

Reaction equation

HRID 1948182 reaction equation
N[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]([CH2:12][CH2:13][N:14]2[CH2:19][CH2:18][CH:17]([O:20][C:21](=[O:35])[NH:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH2:16][CH2:15]2)=[O:11])=[CH:5][CH:4]=1.NC1C=CC(C[OH:42])=CC=1.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.CS(C)=O>C(Cl)Cl>[CH:2]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]([CH2:12][CH2:13][N:14]2[CH2:19][CH2:18][CH:17]([O:20][C:21](=[O:35])[NH:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)[CH2:16][CH2:15]2)=[O:11])=[CH:5][CH:4]=1)=[O:42]

Participants

7

Reactant 5

HCID 679Dimethyl SulfoxideHCID 693314-Aminobenzyl alcoholHCID 81531Diisopropylethylamine2×HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59340340Biphenyl-2-ylcarbamic Acid 1-[2-(4-Aminomethylphenylcarbamoyl)ethyl]piperidin-4-yl Ester

Product 1

HCID 59340337Biphenyl-2-ylcarbamic Acid 1-[2-(4-Formylphenylcarbamoyl)ethyl]piperidin-4-yl EsterYield 66%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A mixture of biphenyl-2-ylcarbamic acid 1-[2-(4-aminomethylphenylcarbamoyl)ethyl]piperidin-4-yl ester (1 g, 2.7 mmol; prepared as described in Preparation 14), 4-aminobenzyl alcohol (498 mg, 4.05 mmol), HATU (1.54 g, 4.05 mmol) and DIPEA (1.41 mL, 8.1 mmol) in DCM (14 mL) was stirred at room temperature for 2 hours. The reaction mixture was diluted with 100 mL of DCM and washed first with a 1:3 mixture of 1N HCl/water (100 mL), then brine (100 mL). The organic layer was dried over MgSO4, filtered and concentrated. The residue was dissolved in DCM (100 mL) and the solution was cooled to −5° C. DIPEA (1.1 mL, 6.33 mmol) and DMSO (1.5 mL, 21.1 mmol) were added to the solution, followed by sulfur trioxide pyridine complex (1 g, 6.33 mmol). The reaction mixture was stirred at 0° C. for 1 hour then washed with a saturated solution of sodium bicarbonate (100 mL) and brine (100 mL). The organic layer was dried over MgSO4, filtered and concentrated to give 0.84 g of the title intermediate (66% yield) as an oil.

Workup

  1. washwashed first with a 1:3 mixture of 1N HCl/water (100 mL)
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in DCM (100 mL)
  6. temperaturethe solution was cooled to −5° C
  7. stirringThe reaction mixture was stirred at 0° C. for 1 hour
  8. washthen washed with a saturated solution of sodium bicarbonate (100 mL) and brine (100 mL)
  9. dry with materialThe organic layer was dried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-be1de1d157a04b24b303c54d01373f88
Source dataset
uspto-grants-2013_03
Patent number
US08399488B2

Linked notes

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