Dimethylformamide → HCID 90118111, compound

HRID 523167Notes

Reaction equation

HRID 523167 reaction equation
Cl[C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[C:4]([C:9]2[CH:14]=[CH:13][C:12]([O:15][CH:16]([CH3:18])[CH3:17])=[CH:11][CH:10]=2)[N:3]=1.C([Sn](CCCC)(CCCC)[C:24]1[N:25]=[CH:26][S:27][CH:28]=1)CCC.[F-].[Cs+].CN(C=O)C>[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC#N.O>[Cl:8][C:6]1[CH:5]=[C:4]([C:9]2[CH:14]=[CH:13][C:12]([O:15][CH:16]([CH3:18])[CH3:17])=[CH:11][CH:10]=2)[N:3]=[C:2]([C:24]2[N:25]=[CH:26][S:27][CH:28]=2)[CH:7]=1

Participants

9

Reactant 4

HCID 6228DimethylformamideHCID 25953Cesium fluorideHCID 27632584-(Tri-n-butylstannyl)thiazole2×HCID 901180792,4-Dichloro-6-(4-isopropoxyphenyl)pyridine

Product 1

HCID 90118111HCID 90118111, compoundYield 26.2%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalyst2×HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

To a 2 dram vial equipped with a stir bar was added 2,4-dichloro-6-(4-isopropoxyphenyl)pyridine (189 mg, 0.668 mmol), 4-(tributylstannyl)thiazole (250 mg, 0.668 mmol), CuI (32 mg, 0.17 mmol), CsF (304 mg, 2.00 mmol), and Pd(PPh3)4 (39 mg, 0.033 mmol). The vial was capped and then placed under N2 atmosphere. To the vial was added DMF (4 mL). The vial was placed in a 80° C. heating block with stirring for 1 h. The mixture was allowed to cool to room temperature. To the reaction was added 4-(tributylstannyl)thiazole (250 mg, 0.668 mmol) and Pd(PPh3)4 (10 mg, 8.9 μmol). The vial was placed under N2 atmosphere and then returned to the 80° C. with stirring for 1 h. The mixture was cooled to room temperature and the mixture was then adsorbed onto diatomaceous earth (Celite®). The resulting powder was subjected to C18 chromatography (water:MeCN, 100:0 to 0:100) to afford 4-(4-chloro-6-(4-isopropoxyphenyl)pyridin-2-yl)thiazole as a dark amber solid (58 mg, 26%). 1H-NMR (500 MHz, CDCl3) δ 8.90 (d, J=2.2 Hz, 1H), 8.36 (d, J=2.2 Hz, 1H), 8.09 (d, J=1.7 Hz, 1H), 8.06-8.02 (m, 2H), 7.63 (d, J=1.7 Hz, 1H), 7.03-6.98 (m, 2H), 4.66 (spt, J=6.1 Hz, 1H), 1.41-1.38 (m, 6H).

Workup

  1. customTo a 2 dram vial equipped with a stir bar
  2. customThe vial was capped
  3. customwas placed in a 80° C.
  4. temperatureheating block
  5. customreturned to the 80° C.
  6. stirringwith stirring for 1 h
  7. temperatureThe mixture was cooled to room temperature

Sources & evidence

ORD record
ord-3ba44f22e7374553a585dc8b756abac4
Source dataset
uspto-grants-2016_05
Patent number
US09334279B2

Reaction notes

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