Methanol → 4-Chloro-2-(2,6-dichloro-4-methoxyphenyl)thiazolo[5,4-c]pyridine

HRID 2366249Notes

Reaction equation

HRID 2366249 reaction equation
[Cl:1][C:2]1[C:7]2[S:8][C:9]([C:11]3[C:16]([Cl:17])=[CH:15][C:14](I)=[CH:13][C:12]=3[Cl:19])=[N:10][C:6]=2[CH:5]=[CH:4][N:3]=1.C(P(C(C)(C)C)C1C=CC2C(=CC=CC=2)C=1C1C2C(=CC=CC=2)C=CC=1)(C)(C)C.[C:49]([O-])([O-])=[O:50].[Cs+].[Cs+].CO>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:1][C:2]1[C:7]2[S:8][C:9]([C:11]3[C:16]([Cl:17])=[CH:15][C:14]([O:50][CH3:49])=[CH:13][C:12]=3[Cl:19])=[N:10][C:6]=2[CH:5]=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 10796Cesium carbonateHCID 2734941(1,1'-Binaphthalen)-2-yldi-tert-butylphosphineHCID 866689974-Chloro-2-(2,6-dichloro-4-iodophenyl)thiazolo[5,4-c]pyridine2×

Product 1

HCID 867233164-Chloro-2-(2,6-dichloro-4-methoxyphenyl)thiazolo[5,4-c]pyridineYield 49.4%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 4-chloro-2-(2,6-dichloro-4-iodophenyl)thiazolo[5,4-c]pyridine (0.300 g, 0.68 mmol), racemic-2-di-t-butylphosphino-1,1′-binaphthyl (0.035 g, 0.0884 mmol), Pd(OAc)2 (0.015 g, 0.068 mmol), Cs2CO3 (0.332 g, 1.02 mmol) and MeOH (0.275 mL, 6.8 mmol) in toluene (3 mL) was degassed with a stream of argon and the reaction mixture was heated at 70° C. for 18 hours. After cooling to room temperature, additional racemic-2-di-t-butylphosphino-1,1′-binaphthyl (0.035 g) and Pd(OAc)2 (0.015 g) were added. The resulting mixture was then degassed with a stream of argon and heated at 70° C. for 18 hours. The crude reaction mixture was filtered through Celite® and the filtrate was combined with two crude reaction mixtures obtained following the same method using 4-chloro-2-(2,6-dichloro-4-iodophenyl)thiazolo[5,4-c]pyridine (0.46 mmol). The volatiles were removed under reduced pressure and the resultant residue was purified by column chromatography on silica gel eluting with 0-10% diethyl ether in petroleum ether to afford the title compound as an off-white solid (116 mg, 30% yield). LCMS (Method D): RT=4.34 min, m/z: 345 [M+H+].

Workup

  1. customwas degassed with a stream of argon
  2. temperatureAfter cooling to room temperature
  3. additionadditional racemic-2-di-t-butylphosphino-1,1′-binaphthyl (0.035 g) and Pd(OAc)2 (0.015 g) were added
  4. customThe resulting mixture was then degassed with a stream of argon
  5. temperatureheated at 70° C. for 18 hours
  6. customThe crude reaction mixture
  7. filtrationwas filtered through Celite®
  8. customreaction mixtures
  9. customobtained
  10. customThe volatiles were removed under reduced pressure
  11. customthe resultant residue was purified by column chromatography on silica gel eluting with 0-10% diethyl ether in petroleum ether

Sources & evidence

ORD record
ord-514a7778f7f04544991e27474ecd16ec
Source dataset
uspto-grants-2014_04
Patent number
US08697708B2

Reaction notes

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