Dichloromethane → 5-[2-(3,4-Dimethoxy-phenyl)-6-methyl-imidazo[2,1-b][1,3,4]thiadiazol-5-yl]-pyridine-2-carbonitrile

HRID 2409531Notes

Reaction equation

HRID 2409531 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].[C:21]([C:23]1[CH:28]=[CH:27][C:26](B2OC(C)(C)C(C)(C)O2)=[CH:25][N:24]=1)#[N:22].C(Cl)Cl.C(=O)([O-])[O-].[Cs+].[Cs+]>COCCOC.O.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:26]4[CH:27]=[CH:28][C:23]([C:21]#[N:22])=[N:24][CH:25]=4)[N:13]3[N:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 164141882-Cyanopyridine-5-boronic acid pinacol esterHCID 667169392-(3,4-Dimethoxy-phenyl)-5-iodo-6-methyl-imidazo[2,1-b][1,3,4]thiadiazole

Product 1

HCID 469136315-[2-(3,4-Dimethoxy-phenyl)-6-methyl-imidazo[2,1-b][1,3,4]thiadiazol-5-yl]-pyridine-2-carbonitrileYield 2%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent2×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 (0.125 g, 0.312 mmol, 1 eq), 2-cyanopyridine-5-boronic acid pinacol ester (0.095 g, 0.414 mmol, 1.33 eq), Pd(dppf)Cl2.DCM (0.008 g, 0.009 mmol, 0.03 eq) and cesium carbonate (0.305 g, 0.935 mmol, 3 eq) in DME (4 mL) and water (0.1 mL) was heated in the microwave oven (45 min, 130° C.), cooled to RT, diluted with water, extracted with EtOAc and washed with brine. The organic layers were dried (MgSO4), filtered and concentrated, and the residue was purified by silica gel chromatography (0-100% DCM in hexane, then 0-3% MeOH in DCM). Product fractions were concentrated to give a solid that was further purified by preparative HPLC affording the pure product (0.002 g, 2% yield). HPLC-MS: (5-100% B in 8 min, 0.8 mL/min): tR=5.52 min, [M+H]+ m/z 378.1. 1H NMR (300 MHz, CDCl3) δ/ppm 9.16 (d, J=1.5, 1H), 8.18 (dd, J=8.4, 2.2, 1H), 7.82-7.67 (m, 1H), 7.41-7.28 (m, 2H), 6.89 (d, J=8.4, 0H), 3.91 (s, 3 H), 3.89 (s, 3 H), 2.54 (s, 1H).

Workup

  1. extractionextracted with EtOAc
  2. washwashed with brine
  3. dry with materialThe organic layers were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customthe residue was purified by silica gel chromatography (0-100% DCM in hexane
  7. concentrationProduct fractions were concentrated
  8. customto give a solid
  9. customthat was further purified by preparative HPLC

Sources & evidence

ORD record
ord-1a4a030bc7c14432b57df06e5f2a5c54
Source dataset
uspto-grants-2014_08
Patent number
US08815918B2

Reaction notes

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