Diisopropylethylamine → HCID 76284154, compound

HRID 1480427Notes

Reaction equation

HRID 1480427 reaction equation
[O:1]=[C:2]1[NH:6][CH:5]=[C:4]([C:7]([OH:9])=O)[O:3]1.[CH3:10][NH:11][CH2:12][CH2:13][CH:14]1[CH2:19][CH2:18][N:17]([C:20]([O:22][CH2:23][C:24]2[CH:29]=[C:28]([Cl:30])[CH:27]=[C:26]([Cl:31])[CH:25]=2)=[O:21])[CH2:16][CH2:15]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CCOC(C)=O>[CH3:10][N:11]([CH2:12][CH2:13][CH:14]1[CH2:15][CH2:16][N:17]([C:20]([O:22][CH2:23][C:24]2[CH:25]=[C:26]([Cl:31])[CH:27]=[C:28]([Cl:30])[CH:29]=2)=[O:21])[CH2:18][CH2:19]1)[C:7]([C:4]1[O:3][C:2](=[O:1])[NH:6][CH:5]=1)=[O:9]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 539814232-Hydroxy-1,3-oxazole-5-carboxylic acidHCID 86722625HCID 86722625, compound

Product 1

HCID 76284154HCID 76284154, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To 2-oxo-2,3-dihydrooxazole-5-carboxylic acid (Example 21, step 1) (317 mg, 1.471 mmol) and 3,5-dichlorobenzyl 4-(2-(methylamino)ethyl)piperidine-1-carboxylate (Example 1, step 3)(508 mg, 1.471 mmol) in DMF (10 ml) was added DIPEA (0.257 ml, 1.471 mmol) and HATU (559 mg, 1.471 mmol). The orange suspension formed was stirred at RT for 16 hrs. The mixture was concentrated under reduced pressure and the residue was dissolved in EtOAc (100 ml). The mixture was filtered and the filtrate was dry loaded in MeOH onto silica (˜5 g). Purification was carried out by chromatography on silica (12 g silica cartridge) eluting with 0-100% EtOAc/iso-hexane. The product fractions were combined and concentrated to give a gum. This was dissolved in minimum volume of EtOAc and applied to a combined 10 g Isolute® PEAX/SCX-2 cartridge. The column was washed with MeOH and the fractions combined and concentrated under reduced pressure. The resultant solid was dissolved in DMSO (500 μl), MeCN (2 ml) and water and applied to a 13 g C18 cartridge which was eluted with 0-100% MeCN/water. The product fractions were combined and concentrated to give an aqueous suspension which was extracted with EtOAc (50 ml). The extracts were dried (MgSO4) and concentrated to give 3,5-dichlorobenzyl 4-(2-(N-methyl-2-oxo-2,3-dihydrooxazole-5-carboxamido)ethyl)piperidine-1-carboxylate as a white solid.

Workup

  1. customThe orange suspension formed
  2. concentrationThe mixture was concentrated under reduced pressure
  3. dissolutionthe residue was dissolved in EtOAc (100 ml)
  4. filtrationThe mixture was filtered
  5. customthe filtrate was dry
  6. customPurification
  7. washeluting with 0-100% EtOAc/iso-hexane
  8. concentrationconcentrated
  9. customto give a gum
  10. washThe column was washed with MeOH
  11. concentrationconcentrated under reduced pressure
  12. dissolutionThe resultant solid was dissolved in DMSO (500 μl)
  13. washwas eluted with 0-100% MeCN/water
  14. concentrationconcentrated
  15. customto give an aqueous suspension which
  16. extractionwas extracted with EtOAc (50 ml)
  17. dry with materialThe extracts were dried (MgSO4)
  18. concentrationconcentrated

Sources & evidence

ORD record
ord-744db75d2e59430884410b6ed82c24ba
Source dataset
uspto-grants-2016_08
Patent number
US09409895B2

Reaction notes

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