Ammonium Chloride → HCID 89544668, compound

HRID 2283432Notes

Reaction equation

HRID 2283432 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([NH:11][CH2:12][C:13]([CH3:18])([CH3:17])[C:14](O)=[O:15])[CH2:9][CH3:10])=[C:4]([F:19])[C:3]=1[C:20]([C:22]1[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=1)=[O:21].[Cl-].[NH4+].CC[N:32](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>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([NH:11][CH2:12][C:13]([CH3:17])([CH3:18])[C:14]([NH2:32])=[O:15])[CH2:9][CH3:10])=[C:4]([F:19])[C:3]=1[C:20]([C:22]1[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=1)=[O:21]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 89544960HCID 89544960, compound

Product 1

HCID 89544668HCID 89544668, compoundYield 5.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Step 5 To a solution of crude 3-{(R)-1-[4-Chloro-2-fluoro-3-(pyridine-3-carbonyl)-phenyl]-propylamino}-2,2-dimethyl-propionic acid (1.15 mmol) in DMF (7 mL) was added ammonium chloride (315 mg, 5.8 mmol, 5 eq), DIPEA (1.41 mL, 8.1 mmol, 7 eq.) and then HATU (661 mg, 1.74 mmol, 1.5 eq.) and the reaction stirred for 18 h. The mixture was partitioned between EtOAc (20 mL) and water (20 mL). The aqueous was extracted with further EtOAc (20 mL) and then the combined organic phase washed with water (3×20 mL) and brine (20 mL) before it was dried (MgSO4), filtered and concentrated. Purified by prepHPLC, basic conditions, and then concentrated. Dissolved in DCM and 1.1 eq. 2 M HCl in Et2O was added. Concentrated and dried in a vacuum oven to give 3-{(R)-1-[4-Chloro-2-fluoro-3-(pyridine-3-carbonyl)-phenyl]-propylamino}-2,2-dimethyl-propionamide (26 mg, 0.06 mmol).

Workup

  1. customThe mixture was partitioned between EtOAc (20 mL) and water (20 mL)
  2. extractionThe aqueous was extracted with further EtOAc (20 mL)
  3. washthe combined organic phase washed with water (3×20 mL) and brine (20 mL) before it
  4. dry with materialwas dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurified by prepHPLC, basic conditions
  8. concentrationconcentrated
  9. dissolutionDissolved in DCM
  10. addition2 M HCl in Et2O was added
  11. concentrationConcentrated
  12. customdried in a vacuum oven

Sources & evidence

ORD record
ord-f3fa67835beb49858f5e038fa3568ea7
Source dataset
uspto-grants-2015_09
Patent number
US09145354B2

Reaction notes

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