Sodium Carbonate → 5-(4-(Ethylsulfonyl)phenyl)-3-(5-(4-((methylamino)methyl)phenyl)-1,3,4-oxadiazol-2-yl)pyrazin-2-amine

HRID 78672Notes

Reaction equation

HRID 78672 reaction equation
Br[C:2]1[N:3]=[C:4]([C:9]2[O:10][C:11]([C:14]3[CH:19]=[CH:18][C:17]([CH2:20][NH:21][CH3:22])=[CH:16][CH:15]=3)=[N:12][N:13]=2)[C:5]([NH2:8])=[N:6][CH:7]=1.[CH2:23]([S:25]([C:28]1[CH:33]=[CH:32][C:31](B(O)O)=[CH:30][CH:29]=1)(=[O:27])=[O:26])[CH3:24].C([O-])([O-])=O.[Na+].[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CS(C)=O.[Pd].O1CCOCC1>[CH2:23]([S:25]([C:28]1[CH:33]=[CH:32][C:31]([C:2]2[N:3]=[C:4]([C:9]3[O:10][C:11]([C:14]4[CH:19]=[CH:18][C:17]([CH2:20][NH:21][CH3:22])=[CH:16][CH:15]=4)=[N:12][N:13]=3)[C:5]([NH2:8])=[N:6][CH:7]=2)=[CH:30][CH:29]=1)(=[O:26])=[O:27])[CH3:24]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 27734204-(Ethylsulphonyl)benzeneboronic acidHCID 594716885-Bromo-3-(5-(4-((methylamino)methyl)phenyl)-1,3,4-oxadiazol-2-yl)pyrazin-2-amine

Product 1

HCID 594716895-(4-(Ethylsulfonyl)phenyl)-3-(5-(4-((methylamino)methyl)phenyl)-1,3,4-oxadiazol-2-yl)pyrazin-2-amineYield 65%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 679Dimethyl SulfoxideSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

To a 0.5-2.0 mL microwave vial 5-bromo-3-[5-[4-(methylaminomethyl)phenyl]-1,3,4-oxadiazol-2-yl]pyrazin-2-amine (100 mg, 0.24 mmol), 4-(ethylsulfonyl)phenylboronic acid (56.72 mg, 0.265 mmol), dioxane (1 mL) and aqueous solution of Na2CO3 (361.3 μL of 2M solution, 0.72 mmol) were added. Palladium; triphenylphosphane (13.91 mg, 0.012 mmol) was then added and the vial sealed. The reaction mixture was heated in the microwave at 150° C. for 30 min. After this time the reaction mixture was diluted with DMSO (2 mL) and filtered before purification by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3 CN) over 16 minutes at 25 mL/min]. The product fractions were collected and evaporated to dryness to give the product as a yellow solid (64.35 mg, 65% yield); 1H NMR (400.0 MHz, DMSO) d 1.14 (t, 3H), 2.64 (s, 3H), 3.33-3.39 (m, 2H), 4.29 (s, 2H), 7.77 (d, 2H), 8.02 (d, 2H), 8.26 (d, 2H), 8.41 (d, 2H), 8.93 (s, 2H) and 9.09 (s, 1H) ppm; MS (ES+) 451.0

Workup

  1. filtrationfiltered before purification by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3 CN) over 16 minutes at 25 mL/min]
  2. customThe product fractions were collected
  3. customevaporated to dryness

Sources & evidence

ORD record
ord-dec5901e1aaa4644a37cba611ee985f6
Source dataset
uspto-grants-2014_09
Patent number
US08841308B2

Reaction notes

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