Potassium Phosphate, Tribasic → Methyl 2-(dimethylphosphoryl)-6-methylisonicotinate

HRID 60074

Reaction equation

HRID 60074 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([CH3:12])[N:11]=1)[C:5]([O:7][CH3:8])=[O:6].[CH3:13][PH:14](=[O:16])[CH3:15].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:13][P:14]([C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([CH3:12])[N:11]=1)[C:5]([O:7][CH3:8])=[O:6])([CH3:15])=[O:16]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 40425123Methyl 2-bromo-6-methylpyridine-4-carboxylateHCID 178503022methylphosphonoylmethane

Product 1

HCID 118228912Methyl 2-(dimethylphosphoryl)-6-methylisonicotinate

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Procedure

Intermediate I-50b was prepared from Intermediate I-50a following a similar procedure as described in WO2009/143389. A solution of methyl 2-bromo-6-methylisonicotinate (I-50a, 690 mg, 3 mmol) in DMF (12 mL) was treated with dimethylphosphine oxide (515 mg, 6.6 mmol), palladium acetate (39 mg, 0.05 mmol), 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene (104 mg, 0.18 mmol) and potassium phosphate (700.5 mg, 3.3 mmol). The mixture was purged with nitrogen and subjected to microwave irradiation (20 min, 150° C.). The reaction mixture was concentrated and purified by column chromatography (9:1:0.175N CH2Cl2/MeOH/NH3 in CH2Cl2, 0% to 100%) to afford methyl 2-(dimethylphosphoryl)-6-methylisonicotinate (I-50b) as an off-white solid. 1H NMR (400 MHz, DMSO) ∂ 8.14 (s, 1H), 7.87 (s, 1H), 3.93 (s, 3H), 2.64 (s, 3H), 1.67 (d, J=13.6 Hz, 6H); MS calculated for C10H15NO3P (M+H+) 228.07. found 228.1.

Workup

  1. customIntermediate I-50b was prepared from Intermediate I-50a
  2. customThe mixture was purged with nitrogen
  3. customsubjected to microwave irradiation (20 min, 150° C.)
  4. concentrationThe reaction mixture was concentrated
  5. custompurified by column chromatography (9:1:0.175N CH2Cl2/MeOH/NH3 in CH2Cl2, 0% to 100%)

Sources & evidence

ORD record
ord-be88b7127d6943b9941508a46ba445f0
Source dataset
uspto-grants-2016_09
Patent number
US09440957B2

Linked notes

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