Sodium Carbonate → HCID 46941215, compound

HRID 2409597Notes

Reaction equation

HRID 2409597 reaction equation
[F:1][C:2]([F:20])([F:19])[C:3]1[C:4]([NH2:18])=[N:5][CH:6]=[C:7]([C:9]2[S:13][C:12]3=[N:14][CH:15]=[C:16](I)[N:11]3[N:10]=2)[CH:8]=1.[F:21][C:22]1[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][N:23]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.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>[F:21][C:22]1[N:23]=[CH:24][C:25]([C:16]2[N:11]3[C:12]([S:13][C:9]([C:7]4[CH:8]=[C:3]([C:2]([F:20])([F:19])[F:1])[C:4]([NH2:18])=[N:5][CH:6]=4)=[N:10]3)=[N:14][CH:15]=2)=[CH:26][CH:27]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2783397(6-Fluoropyridin-3-yl)boronic acidHCID 66716934HCID 66716934, compound

Product 1

HCID 46941215HCID 46941215, compoundYield 53%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

3-(trifluoromethyl)-5-(5-iodoimidazo[2,1-b][1,3,4]thiadiazol-2-yl)pyridin-2-amine (0.100 g, 0.243 mmol, 1 eq) was dissolved in dioxane (1.5 mL), then 2-fluoropyridine-5-boronic acid (0.055 g, 0.389 mmol, 1.6 eq) was added followed by 2M aq. Na2CO3 (0.5 mL, 4 eq). The suspension was degassed (N2, 15 min) and equipped with an argon balloon. Pd(Ph3P)2Cl2 (0.043 g, 0.061 mmol, 0.25 eq) was quickly added, and the reaction flask was placed in a pre-heated bath (115° C.). After stirring at reflux temperature for 3 h the mixture was cooled to RT and concentrated. The residue was suspended in EtOAc and water, and the clear water phase was removed. The remainder was concentrated to dryness and triturated with Et2O, filtered off, washed with Et2O and dried in vacuo to afford the desired product (0.049 g, 53%). HPLC-MS (5-100% B in 8 min at 0.8 mL): tR=5.14 min, [M+H]+ m/z 381.0; 1H-NMR (DMSO-d6): δ=8.93 (1H ,bs), 8.84 (1H, bs), 8.67-8.58 (1H, m), 8.24 (1H, bs), 7.92 (1H, s), 7.42-7.34 (3H, m) ppm

Workup

  1. customThe suspension was degassed (N2, 15 min)
  2. customequipped with an argon balloon
  3. customthe reaction flask was placed in a pre-heated bath
  4. custom(115° C.)
  5. temperatureat reflux temperature for 3 h the mixture
  6. concentrationconcentrated
  7. customwater, and the clear water phase was removed
  8. concentrationThe remainder was concentrated to dryness
  9. customtriturated with Et2O
  10. filtrationfiltered off
  11. washwashed with Et2O
  12. customdried in vacuo

Sources & evidence

ORD record
ord-c365b2fcbbdb4bc3b25f5695230ca5e2
Source dataset
uspto-grants-2014_08
Patent number
US08815918B2

Reaction notes

Loading…