Potassium Carbonate → 2-(3,4-Dimethoxy-phenyl)-6-methyl-5-pyridin-3-yl-imidazo[2,1-b][1,3,4]thiadiazole

HRID 2409533Notes

Reaction equation

HRID 2409533 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[S:15][C:14]3=[N:16][C:17]([CH3:20])=[C:18](I)[N:13]3[N:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23](B(O)O)[CH:22]=1.C(=O)([O-])[O-].[K+].[K+]>COCCOC.C(Cl)Cl.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][C:17]([CH3:20])=[C:18]([C:23]4[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=4)[N:13]3[N:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27343783-Pyridinylboronic acid2×HCID 667169392-(3,4-Dimethoxy-phenyl)-5-iodo-6-methyl-imidazo[2,1-b][1,3,4]thiadiazole

Product 1

HCID 469409482-(3,4-Dimethoxy-phenyl)-6-methyl-5-pyridin-3-yl-imidazo[2,1-b][1,3,4]thiadiazoleYield 89.7%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×HCID 6344DichloromethaneSolvent3×HCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of 2-(3,4-dimethoxy-phenyl)-5-iodo-6-methyl-imidazo[2,1-b][1,3,4]thiadiazole (0.070 g, 0.174 mmol), pyridine-3-boronic acid (0.026 g, 0.209 mmol), Pd(dppf)Cl2.DCM (0.014 g. 0.017 mmol) and potassium carbonate (0.5 mL, sat. aq) in DME (1.7 mL) was heated in the microwave oven at 150° C. for 2 h. Since the conversion was incomplete, another 1.2 eq of pyridine-3-boronic acid and 0.1 eq of Pd(dppf)Cl2.DCM were added, and the mixture was subjected to another 7 hours of microwave irradiation at 150° C. The reaction mixture was cooled, diluted with DCM, washed with water, dried (Na2SO4) and concentrated. A yellow solid (0.055 g) was obtained that was purified by silica gel chromatography (cyclohexane/0-60% EtOAc) to give the desired product (white solid, 0.042 g, 39%). HPLC-MS: (5-100% B in 8 min, 0.8 mL/min, 50° C.): tR=4.09 min, [M+H]+ m/z 353.1. 1H NMR (300 MHz, CDCl3) δ/ppm 9.00 (d, J=2.2, 1H), 8.53 (dd, J=4.8, 1.6, 1H), 8.00 (dd, J=8.0, 1.8, 1H), 7.48-7.29 (m, 3H), 6.88 (d, J=9.0, 1H), 3.90 (d, J=5.0, 7H), 2.50 (s, 3H).

Workup

  1. customthe mixture was subjected to another 7 hours of microwave irradiation at 150° C
  2. temperatureThe reaction mixture was cooled
  3. washwashed with water
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-0bc3fcea572f41a482b9b2645b000707
Source dataset
uspto-grants-2014_08
Patent number
US08815918B2

Reaction notes

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