Hydrochloric Acid → [2-Bromo-5-(4-chlorophenyl)pyridin-3-yl]methylamine

HRID 734870Notes

Reaction equation

HRID 734870 reaction equation
C=O.[C:3]([BH3-])#[N:4].[Na+].[Br:7][C:8]1[C:13](N)=[CH:12][C:11]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=2)=[CH:10][N:9]=1.Cl.C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C.CC(O)=O>[Br:7][C:8]1[C:13]([CH2:3][NH2:4])=[CH:12][C:11]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=2)=[CH:10][N:9]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 10340Sodium CarbonateHCID 5003444Sodium cyanoborohydrideHCID 859697042-Bromo-5-(4-chloro-phenyl)-pyridin-3-ylamine

Product 1

HCID 86601137[2-Bromo-5-(4-chlorophenyl)pyridin-3-yl]methylamine

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6342AcetonitrileSolvent

Procedure

1.32 mL (17.63 mmol) of formalin solution (37% in water) and 443 mg (7.05 mmol) of sodium cyanoborohydride were added to a solution of 0.50 g (1.76 mmol) of 2-bromo-5-(4-chlorophenyl)pyridin-3-ylamine (Example 16.1c) in 20 mL of acetonitrile, the mixture was acidified to pH 4 with HOAc, and stirred for 16 hours at RT. The reaction mixture was acidified with 4M aqueous HCl and stirred for 1 hour at RT. It was made alkaline with sat. aqueous sodium carbonate solution and the aqueous phase was exhaustively extracted with DCM. The combined organic phases were dried over magnesium sulfate and evaporated down in vacuo. The residue was purified by chromatography (silica gel, gradient PE/DCM 50:50→100:0). Yield: 0.24 g (46% of theoretical); C12H10BrClN2 (M=297.578); calc.: molpeak (M+H)+: 297/299/301 (BrCl); found: molpeak (M+H)+:297/299/301 (BrCl); HPLC-MS: 6.09 minutes (method B).

Workup

  1. stirringstirred for 1 hour at RT
  2. extractionthe aqueous phase was exhaustively extracted with DCM
  3. dry with materialThe combined organic phases were dried over magnesium sulfate
  4. customevaporated down in vacuo
  5. customThe residue was purified by chromatography (silica gel, gradient PE/DCM 50:50→100:0)
  6. custom6.09 minutes (method B)

Sources & evidence

ORD record
ord-9c9580a458284edb993b0882e5151c77
Source dataset
uspto-grants-2009_09
Patent number
US07592358B2

Reaction notes

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