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

HRID 2409561Notes

Reaction equation

HRID 2409561 reaction equation
[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]

Participants

5

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

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

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-a5cccfe820fd4a7baf69cf33a0e96471
Source dataset
uspto-grants-2014_08
Patent number
US08815918B2

Reaction notes

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