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 2409568노트

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HRID 2409568 반응식
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]

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 178418476HCID 178418476, 화합물촉매HCID 962Water용매2회HCID 312751,4-Dioxane용매

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온도
105 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-d31668d4a30642abb40b1dca1d7c9de1
출처 데이터셋
uspto-grants-2014_08
특허 번호
US08815918B2

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