Sodium Carbonate → N-Methyl-4-phenyl-3-pyridinamine

HRID 878382Notes

Reaction equation

HRID 878382 reaction equation
F[C:2]1[C:7](F)=[CH:6][C:5]([C:9]2[CH:14]=[CH:13][N:12]=[CH:11][C:10]=2[N:15](CCS(C)(=O)=O)[C:16](=O)C2C=C(C(F)(F)F)N=C(C(F)(F)F)C=2)=[C:4](OC)[CH:3]=1.C1(B(O)O)C=CC=CC=1.C([O-])([O-])=O.[Na+].[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C([O-])(O)=O.[Na+]>COCCOC.CC([O-])=O.CC([O-])=O.[Pd+2].CCOC(C)=O>[CH3:16][NH:15][C:10]1[CH:11]=[N:12][CH:13]=[CH:14][C:9]=1[C:5]1[CH:4]=[CH:3][CH:2]=[CH:7][CH:6]=1

Participants

9

Reactant 5

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 66827Phenylboronic AcidHCID 516892Sodium BicarbonateHCID 86670771N-[4-(4,5-Difluoro-2-methoxy-phenyl)-pyridin-3-yl]-N-(2-methanesulfonyl-ethyl)-2,6-bis-trifluoromethyl-isonicotinamide2×

Product 1

HCID 70663229N-Methyl-4-phenyl-3-pyridinamineYield 90.5%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of (4-iodo-pyridin-3-yl)-methyl-amine (225 mg, 0.96 mmol, example 36, intermediate b) in DME (5 mL) were added phenyl boronic acid (234 mg, 1.92 mmol) and 2M aqueous Na2CO3 solution (2 mL) and the reaction mixture was purged with nitrogen for 15 min. Then Pd(OAc)2 (22 mg, 0.1 mmol) and triphenylphosphine (50 mg, 0.19 mmol) were added and the reaction mixture was stirred at 100° C. for 5 hours. The reaction mixture was poured on 30 mL 10% aqueous NaHCO3 solution and 30 mL EtOAc and the layers were separated. The aqueous layer was extracted with 30 mL EtOAc. The combined organic layer was washed with brine (30 mL), dried over Na2SO4 and evaporated. The residue was purified by column chromatography eluting with a gradient of n-hexane:EtOAc (80:20 to 70:30) to yield the desired compound as a yellow solid (160 mg, 90%) MS (ESI): m/z=185.0 [M+H]+.

Workup

  1. customthe reaction mixture was purged with nitrogen for 15 min
  2. customthe layers were separated
  3. extractionThe aqueous layer was extracted with 30 mL EtOAc
  4. washThe combined organic layer was washed with brine (30 mL)
  5. dry with materialdried over Na2SO4
  6. customevaporated
  7. customThe residue was purified by column chromatography
  8. washeluting with a gradient of n-hexane:EtOAc (80:20 to 70:30)

Sources & evidence

ORD record
ord-8373ba4d06194144aef44348cf1dad54
Source dataset
uspto-grants-2015_03
Patent number
US08987307B2

Reaction notes

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