Sodium Carbonate → HCID 46941213, compound

HRID 2409593Notes

Reaction equation

HRID 2409593 reaction equation
C([O-])([O-])=O.[Na+].[Na+].[F:7][C:8]1[CH:13]=[C:12]([F:14])[CH:11]=[CH:10][C:9]=1[S:15]([NH:18][C:19]1[C:20]([O:34][CH3:35])=[N:21][CH:22]=[C:23]([C:25]2[S:29][C:28]3=[N:30][CH:31]=[C:32](I)[N:27]3[N:26]=2)[CH:24]=1)(=[O:17])=[O:16].[N:36]1[CH:41]=[CH:40][C:39](B2OC(C)(C)C(C)(C)O2)=[CH:38][N:37]=1>O1CCOCC1>[F:7][C:8]1[CH:13]=[C:12]([F:14])[CH:11]=[CH:10][C:9]=1[S:15]([NH:18][C:19]1[C:20]([O:34][CH3:35])=[N:21][CH:22]=[C:23]([C:25]2[S:29][C:28]3=[N:30][CH:31]=[C:32]([C:40]4[CH:39]=[CH:38][N:37]=[N:36][CH:41]=4)[N:27]3[N:26]=2)[CH:24]=1)(=[O:17])=[O:16]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 457872814-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridazineHCID 53476078HCID 53476078, compound

Product 1

HCID 46941213HCID 46941213, compoundYield 5.5%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

Dioxane (2 mL) and 2M aq Na2CO3 (0.5 mL) were added to 2,4-difluoro-N-[2-methoxy-5-(5-iodoimidazo[2,1-b][1,3,4]thiadiazol-2-yl)-pyridin-3-yl]-benzenesulfon-amide (100 mg) and pyridazin-4-boronic acid pinacol ester (80 mg), and the suspension was degassed under vacuum and filled with argon (2×). The catalyst (30 mg) was quickly added, and the reaction mixture was stirred at reflux for 2 h. Further boronate (50 mg) was added, and the mixture was degassed again, then more catalyst was added (25 mg) and stirring was continued at reflux for 4 h. The solvents were evaporated, and the residue was stirred in water for 36 h. The precipitate that had formed was removed by filtration, and the filtrate was concentrated and taken up in aq. NH4Cl. A precipitate formed overnight and was filtered off, washed with water followed by ether and dried. The solid was purified by flash chromatography (DCM/MeOH 98:2 to 9:1, affording 24 mg of crude product) and subsequently by preparative HPLC to give the desired product (5 mg). HPLC-MS (5-100% B in 8 min at 0.8 mL): tR=4.57 min, [M+H]+ m/z 502.1; 1H NMR (300 MHz, DMSO) δ=10.56 (s, 1H), 9.82 (s, 1H), 9.25 (d, J=5.5 Hz, 1H), 8.57 (s, 1H), 8.35-8.16 (m, 2H), 8.06 (s, 1H), 7.79 (dd, J=15.0, 8.6 Hz, 1H), 7.50 (s, 1H), 7.20 (t, J=8.3 Hz, 1H), 3.70 (s, 3H) ppm.

Workup

  1. customthe suspension was degassed under vacuum
  2. additionfilled with argon (2×)
  3. additionThe catalyst (30 mg) was quickly added
  4. temperatureat reflux for 2 h
  5. additionFurther boronate (50 mg) was added
  6. customthe mixture was degassed again
  7. additionmore catalyst was added (25 mg)
  8. stirringstirring
  9. temperatureat reflux for 4 h
  10. customThe solvents were evaporated
  11. stirringthe residue was stirred in water for 36 h
  12. customThe precipitate that had formed
  13. customwas removed by filtration
  14. concentrationthe filtrate was concentrated
  15. customA precipitate formed overnight
  16. filtrationwas filtered off
  17. washwashed with water
  18. customdried
  19. customThe solid was purified by flash chromatography (DCM/MeOH 98:2 to 9:1, affording 24 mg of crude product) and subsequently by preparative HPLC

Sources & evidence

ORD record
ord-2419b720d14e4d2caef38401d63fb2f1
Source dataset
uspto-grants-2014_08
Patent number
US08815918B2

Reaction notes

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