Potassium Phosphate, Tribasic → (2'-Fluoro-3-methyl-2,4'-bipyridin-5-yl)methanamine

HRID 711239Notes

Reaction equation

HRID 711239 reaction equation
Cl.Cl[C:3]1[N:8]=[CH:7][C:6]([CH2:9][NH2:10])=[CH:5][C:4]=1[CH3:11].[F:12][C:13]1[CH:18]=[C:17](B(O)O)[CH:16]=[CH:15][N:14]=1.COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CC([O-])=O.CC([O-])=O.[Pd+2]>[F:12][C:13]1[CH:18]=[C:17]([C:3]2[C:4]([CH3:11])=[CH:5][C:6]([CH2:9][NH2:10])=[CH:7][N:8]=2)[CH:16]=[CH:15][N:14]=1

Participants

6

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27833962-Fluoropyridine-4-boronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 53395592(6-Chloro-5-methylpyridin-3-yl)methanamine hydrochloride

Product 1

HCID 67208684(2'-Fluoro-3-methyl-2,4'-bipyridin-5-yl)methanamine

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Procedure

To a reaction vial was added (6-chloro-5-methylpyridin-3-yl)methanamine HCl salt 30-4 (738 mg, 3.8 mmol), 2-fluoropyridin-4-ylboronic acid 30-5 (800 mg, 5.7 mmol), Pd(OAc)2 (106 mg, 0.47 mmol), S-Phos (194 mg, 0.47 mmol) and K3PO4 (2.0 g, 9.5 mmol). The vial was evacuated and backfilled with nitrogen, and 2-butanol (5 mL) was added via syringe. The reaction was stirred at room temperature for 10 mins and then 100° C. for 3 hours. After cooling to room temperature, the reaction mixture was partitioned between DCM and H2O, and extracted with DCM three times. The organic phase was combined and dried. The crude product was purified by silica gel flash chromatography, eluted with 10% methanol in DCM to give (2′-fluoro-3-methyl-2,4′-bipyridin-5-yl)methanamine 30-5. MS m/z 218.2 (M+1).

Workup

  1. customThe vial was evacuated
  2. additionwas added via syringe
  3. wait100° C. for 3 hours
  4. temperatureAfter cooling to room temperature
  5. customthe reaction mixture was partitioned between DCM and H2O
  6. extractionextracted with DCM three times
  7. customdried
  8. customThe crude product was purified by silica gel flash chromatography
  9. washeluted with 10% methanol in DCM

Sources & evidence

ORD record
ord-3518541786da4c3b9ec46e1b2a1d89fd
Source dataset
uspto-grants-2015_11
Patent number
US09181235B2

Reaction notes

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