Dimethylformamide → 2-methyl-6-(thiazol-2-yl)-N-(1-(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)ethyl)isonicotinamide

HRID 623656Notes

Reaction equation

HRID 623656 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:22]=[C:23]([CH3:25])[N:24]=1)[C:5]([NH:7][CH:8]([C:10]1[CH:11]=[N:12][C:13]([O:16][CH2:17][C:18]([F:21])([F:20])[F:19])=[CH:14][CH:15]=1)[CH3:9])=[O:6].C([Sn](CCCC)(CCCC)[C:31]1[S:32][CH:33]=[CH:34][N:35]=1)CCC.CN(C)C=O>C(OCC)(=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:25][C:23]1[CH:22]=[C:4]([CH:3]=[C:2]([C:31]2[S:32][CH:33]=[CH:34][N:35]=2)[N:24]=1)[C:5]([NH:7][CH:8]([C:10]1[CH:11]=[N:12][C:13]([O:16][CH2:17][C:18]([F:21])([F:19])[F:20])=[CH:14][CH:15]=1)[CH3:9])=[O:6]

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 27632592-(Tributylstannyl)-1,3-thiazoleHCID 874269462-bromo-6-methyl-N-(1-(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)ethyl)isonicotinamide

Product 1

HCID 675098912-methyl-6-(thiazol-2-yl)-N-(1-(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)ethyl)isonicotinamideYield 11%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 2-bromo-6-methyl-N-(1-(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)ethyl)isonicotinamide (25 mg, 0.060 mmol, Step-1, single enantiomer), 2-tributylstannylthiazole (27 mg, 0.072 mmol), bis(triphenylphosphine)palladium(II) dichloride (8.4 mg, 0.012 mmol) and N,N-dimethylformamide (1 mL) is stirred at 120° C. under nitrogen atmosphere for 6 hours. After cooling to room temperature, the mixture is diluted with ethyl acetate (20 mL) and washed with water (20 mL). The organic layer is dried over sodium sulfate and concentrated under reduced pressure. The residue is purified by a strong cation exchange cartridge (BondElute(registered trademark) SCX, 1 g/6 mL, Varian Inc.) and then by preparative LC-MS to give 2.7 mg (11% yield) of the title compound.

Workup

  1. temperatureAfter cooling to room temperature
  2. washwashed with water (20 mL)
  3. dry with materialThe organic layer is dried over sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue is purified by a strong cation exchange cartridge (BondElute(registered trademark) SCX, 1 g/6 mL, Varian Inc

Sources & evidence

ORD record
ord-2fe9d8450c8b4022baba59cf3a50b4ef
Source dataset
uspto-grants-2016_04
Patent number
US09302991B2

Reaction notes

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