Potassium Carbonate → N-{3-[5-(6-Amino-5-trifluoromethyl-pyridin-3-yl)-imidazo[2,1-b][1,3,4]thiadiazol-2-yl]-benzyl}-methanesulfonamide

HRID 2409568Notes

Reaction equation

HRID 2409568 reaction equation
I[C:2]1[N:9]2[C:5]([S:6][C:7]([C:10]3[CH:11]=[C:12]([CH:19]=[CH:20][CH:21]=3)[CH2:13][NH:14][S:15]([CH3:18])(=[O:17])=[O:16])=[N:8]2)=[N:4][CH:3]=1.CC1(C)C(C)(C)OB([C:30]2[CH:31]=[C:32]([C:37]([F:40])([F:39])[F:38])[C:33]([NH2:36])=[N:34][CH:35]=2)O1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.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>[NH2:36][C:33]1[N:34]=[CH:35][C:30]([C:2]2[N:9]3[C:5]([S:6][C:7]([C:10]4[CH:11]=[C:12]([CH:19]=[CH:20][CH:21]=4)[CH2:13][NH:14][S:15]([CH3:18])(=[O:17])=[O:16])=[N:8]3)=[N:4][CH:3]=2)=[CH:31][C:32]=1[C:37]([F:40])([F:38])[F:39]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 468641035-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-3-(trifluoromethyl)pyridin-2-amineHCID 66717200N-[3-(5-Iodo-imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-benzyl]-methanesulfonamide

Product 1

HCID 66717139N-{3-[5-(6-Amino-5-trifluoromethyl-pyridin-3-yl)-imidazo[2,1-b][1,3,4]thiadiazol-2-yl]-benzyl}-methanesulfonamideYield 6%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
105 °C

Procedure

N-[3-(5-Iodo-imidazo[2,1-b][1,3,4]thiadiazol-2-yl) -benzyl]-methanesulfonamide (77 mg, 0.177 mmol, 1 eq) was dissolved in 1,4-dioxane (3 mL) and 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3-trifluoromethyl-pyridin-2-ylamine (76 mg, 0.265 mmol, 1.5 eq), K2CO3 (73 mg, 0.531 mmol, 3 eq), H2O (2 mL) and dichlorobis(triphenylphosphine)palladium(II)(12 mg, 0.0177 mmol, 0.1 eq) were added. The reaction mixture was heated in a pressure tube at 105° C. overnight. Solvents were removed and the residue obtained was suspended in water and extracted twice with EtOAc. The organic layers were dried, filtered end evaporated. The residue was triturated with CH3CN and filtered. The solid was purified in an Isolute Si II cartridge (DCM/MeOH, 0%-5%). The product obtained was precipitated in CH3CN and filtered to give the desired product (5 mg, 6%). HPLC-MS (5-100% B in 8 min at 0.8 mL): tR=4.70 min, [M+H]+ m/z 469.1; 1H NMR (300 MHz, DMSO) δ 8.88 (s, 1H), 8.35 (s, 1H), 7.95 (s, 1H), 7.90 (m, 1H), 7.80 (s, 1H), 7.73 (t, J=6.3 Hz, 1H), 7.62 (d, J=4.7 Hz, 2H), 6.74 (s, 2H), 4.29 (d, J=6.3 Hz, 2H), 2.93 (s, 3H).

Workup

  1. customSolvents were removed
  2. customthe residue obtained
  3. extractionextracted twice with EtOAc
  4. customThe organic layers were dried
  5. filtrationfiltered end
  6. customevaporated
  7. customThe residue was triturated with CH3CN
  8. filtrationfiltered
  9. customThe solid was purified in an Isolute Si II cartridge (DCM/MeOH, 0%-5%)
  10. customThe product obtained
  11. customwas precipitated in CH3CN
  12. filtrationfiltered

Sources & evidence

ORD record
ord-d31668d4a30642abb40b1dca1d7c9de1
Source dataset
uspto-grants-2014_08
Patent number
US08815918B2

Reaction notes

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