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

HRID 2409561

反応式

HRID 2409561 の反応式
[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]

参加物

5

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

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

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-a5cccfe820fd4a7baf69cf33a0e96471
出典データセット
uspto-grants-2014_08
特許番号
US08815918B2

関連ノート

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