Acetic Acid → HCID 89544943, compound

HRID 2283447Notes

Reaction equation

HRID 2283447 reaction equation
[NH2:1][C@@H:2]([C:5]1[C:6]([F:21])=[C:7]([C:12]([C:14]2[CH:15]=[N:16][C:17]([NH2:20])=[CH:18][CH:19]=2)=[O:13])[C:8]([Cl:11])=[CH:9][CH:10]=1)[CH2:3][CH3:4].C=O.[C:24](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>C(Cl)Cl.[OH-].[Na+].O>[NH2:20][C:17]1[N:16]=[CH:15][C:14]([C:12]([C:7]2[C:8]([Cl:11])=[CH:9][CH:10]=[C:5]([C@H:2]([NH:1][CH3:24])[CH2:3][CH3:4])[C:6]=2[F:21])=[O:13])=[CH:19][CH:18]=1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 89544538HCID 89544538, compound

Product 1

HCID 89544943HCID 89544943, compoundYield 3.2%

Reagents, catalysts & solvents 3

HCID 14798Sodium HydroxideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

A mixture of [3-((R)-1-Amino-propyl)-6-chloro-2-fluoro-phenyl]-(6-amino-pyridin-3-yl)-methanone (100 mg, 0.29 mmol), paraformaldehyde (26 mg, 0.87 mmol), sodium triacetoxyborohydride (92 mg, 0.44 mmol) and acetic acid (67 μL, 1.16 mmol) in DCM (0.5 mL) was stirred for 18 h. Chromatographic analysis showed mainly bis-addition peaks, but a small peak for product. Further DCM (5 mL) and water (5 mL) were added and the mixture was made basic with a few drops of 5M NaOH. Separated and aqueous extracted with further DCM (5 mL). The combined organic phase was washed with brine (4 mL), dried (MgSO4), filtered and concentrated. Purified by prep LCMS (basic 3) and concentrated to give (6-Amino-pyridin-3-yl)-[6-chloro-2-fluoro-3-((R)-1-methylamino-propyl)-phenyl]-methanone (3 mg). Dissolved in d6-DMSO (160 uL) and concentration determined by NMR—53 mM. Used as solution for assays. [MH]+ 322.

Workup

  1. customSeparated
  2. extractionaqueous extracted with further DCM (5 mL)
  3. washThe combined organic phase was washed with brine (4 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurified by prep LCMS (basic 3)
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-813652d55ed640268c2148cfb682f11f
Source dataset
uspto-grants-2015_09
Patent number
US09145354B2

Reaction notes

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