Potassium Carbonate → 2-(3,4-Dimethoxy-phenyl)-5-(2-methylsulfanyl-pyrimidin-5-yl)-imidazo[2,1-b][1,3,4]thiadiazole

HRID 2409561

반응식

HRID 2409561 반응식
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[S:15][C:14]3=[N:16][CH:17]=[C:18](I)[N:13]3[N:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[CH3:20][S:21][C:22]1[N:27]=[CH:26][C:25](B2OC(C)(C)C(C)(C)O2)=[CH:24][N:23]=1.C([O-])([O-])=O.[K+].[K+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[S:15][C:14]3=[N:16][CH:17]=[C:18]([C:25]4[CH:24]=[N:23][C:22]([S:21][CH3:20])=[N:27][CH:26]=4)[N:13]3[N:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]

참가 물질

5

반응물 3

HCID 11430Potassium CarbonateHCID 164142192-(Methylthio)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidineHCID 667169462-(3,4-Dimethoxy-phenyl)-5-iodo-imidazo[2,1-b][1,3,4]thiadiazole

생성물 1

HCID 667169862-(3,4-Dimethoxy-phenyl)-5-(2-methylsulfanyl-pyrimidin-5-yl)-imidazo[2,1-b][1,3,4]thiadiazole수율 73%

시약·촉매·용매 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매

실험 절차

A mixture of 2-(3,4-dimethoxy-phenyl)-5-iodo-imidazo[2,1-b][1,3,4]thiadiazole (0.25 g, 0.646 mmol, 1 eq), 2-(methylthio)pyrimidine-5-boronic acid pinacol ester (0.244 g, 0.968 mmol, 1.5 eq) and K2CO3 (0.357 g, 2.584 mmol, 4 eq) in 1,2-DME/H2O (9/1, 5 mL) was stirred at RT for 10 min. Then, PdCl2(dppf) (0.053 g, 0.0646 mmol, 0.1 eq) was added and the reaction mixture was heated at 85° C. for 4 h. Solvents were evaporated and water was added to the residue. The suspension was extracted with EtOAc (×3) and the combined organics were dried, filtered and evaporated. The residue was purified in an Isolute Si II cartridge using MeOH in DCM (0% to 1%) to give the desired product (47 mg). The aqueous phase was evaporated to dryness and the residue was redissolved in DCM and filtered. The filtrate was evaporated and purified as described before to give additional desired product (136 mg). Total amount obtained: 183 mg. Overall yield: 73%. HPLC-MS: (5-100% B in 8 min, 0.8 mL/min, 50° C.): tR=5.46 min, [M+H]+ m/z 386.2; 1H NMR (300 MHz, CDCl3) δ 9.15 (d, J=5.8 Hz, 2H), 7.64 (s, 1H), 7.45 (m, 2H), 6.97 (m, 1H), 3.99 (s, 3H), 3.98 (s, 3H), 2.64 (s, 3H).

후처리

  1. temperaturethe reaction mixture was heated at 85° C. for 4 h
  2. customSolvents were evaporated
  3. additionwater was added to the residue
  4. extractionThe suspension was extracted with EtOAc (×3)
  5. customthe combined organics were dried
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified in an Isolute Si II cartridge

출처 및 근거

ORD 기록
ord-a5cccfe820fd4a7baf69cf33a0e96471
출처 데이터셋
uspto-grants-2014_08
특허 번호
US08815918B2

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