D-Pyroglutamic acid → (R)-N-((1-(5-oxopyrrolidine-2-carbonyl)piperidin-4-yl)methyl)-3,5-bis(trifluoromethyl)benzamide

HRID 388776

Reaction equation

HRID 388776 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([CH2:7][NH:8][C:9](=[O:24])[C:10]2[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[C:12]([C:20]([F:23])([F:22])[F:21])[CH:11]=2)[CH2:3][CH2:2]1.[O:25]=[C:26]1[NH:30][C@@H:29]([C:31](O)=[O:32])[CH2:28][CH2:27]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C([O-])(O)=O.[Na+]>CN(C=O)C.CCOC(C)=O>[O:25]=[C:26]1[NH:30][C@@H:29]([C:31]([N:1]2[CH2:6][CH2:5][CH:4]([CH2:7][NH:8][C:9](=[O:24])[C:10]3[CH:11]=[C:12]([C:20]([F:21])([F:22])[F:23])[CH:13]=[C:14]([C:16]([F:18])([F:19])[F:17])[CH:15]=3)[CH2:3][CH2:2]2)=[O:32])[CH2:28][CH2:27]1

Participants

7

Reactant 4

HCID 439685D-Pyroglutamic acidHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57993323N-(piperidin-4-ylmethyl)-3,5-bis(trifluoromethyl)benzamide

Product 1

HCID 57993336(R)-N-((1-(5-oxopyrrolidine-2-carbonyl)piperidin-4-yl)methyl)-3,5-bis(trifluoromethyl)benzamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-20 °C

Procedure

A solution of N-(piperidin-4-ylmethyl)-3,5-bis(trifluoromethyl)benzamide (48 mg, 0.14 mmol), TEA (95 μL, 0.68 mmol), and (R)-5-oxopyrrolidine-2-carboxylic acid (20.66 mg, 0.16 mmol) in DMF (1.5 mL) was treated with a solution of HATU (77 mg, 0.20 mmol) in DMF (1 mL). The reaction mixture was stirred overnight then transferred to a test tube containing saturated aqueous NaHCO3 (4 mL) and EtOAc (4 mL). The biphasic mixture was mixed vigorously and allowed to separate for 15 min. After separation, the mixture was cooled to −20° C. until the aqueous layer was frozen. The organic layer was then poured off and the solvent was removed in vacuo at 50° C. The resulting residue was dissolved in CH2Cl2 (1 mL) and treated with 2M HCl in Et2O (3 mL) and allowed to stir overnight at room temperature. The solvent was removed under reduced pressure and the crude solid was purified by HiTOPs.

Workup

  1. customthen transferred to a test tube
  2. additionThe biphasic mixture was mixed vigorously
  3. customto separate for 15 min
  4. customAfter separation
  5. temperaturewas frozen
  6. additionThe organic layer was then poured off
  7. customthe solvent was removed in vacuo at 50° C
  8. dissolutionThe resulting residue was dissolved in CH2Cl2 (1 mL)
  9. additiontreated with 2M HCl in Et2O (3 mL)
  10. stirringto stir overnight at room temperature
  11. customThe solvent was removed under reduced pressure
  12. customthe crude solid was purified by HiTOPs

Sources & evidence

ORD record
ord-6142d6679ef243fdaf6c56ccb601f45f
Source dataset
uspto-grants-2013_02
Patent number
US08377968B2

Linked notes

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