2-Bromothiazole-5-carboxylic acid → HCID 66654677, compound

HRID 2367734Notes

Reaction equation

HRID 2367734 reaction equation
Br[C:2]1[S:3][C:4]([C:7]([OH:9])=[O:8])=[CH:5][N:6]=1.[N:10]1[CH:15]=[CH:14][C:13](B(O)O)=[CH:12][C:11]=1[CH3:19]>CN1C(=O)CCC1.C([O-])([O-])=O.[Na+].[Na+].[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:19][C:11]1[CH:12]=[C:13]([C:2]2[S:3][C:4]([C:7]([OH:9])=[O:8])=[CH:5][N:6]=2)[CH:14]=[CH:15][N:10]=1

Participants

6

Reactant 2

HCID 27632102-Bromothiazole-5-carboxylic acidHCID 41926642-Methylpyridine-4-boronic acid

Product 1

HCID 66654677HCID 66654677, compound

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 10340Sodium CarbonateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
100 °C

Procedure

Bubble argon through a suspension of 2-bromothiazole-5-carboxylic acid (75 mg, 0.36 mmol), 2-picoline-4-boronic acid (59 mg, 0.43 mmol), and tetrakis-(triphenylphosphine)-palladium(0) (42 mg) in NMP (1 mL) and 2M Na2CO3 (0.25 mL). Stir the sealed vial at 100° C. for 4 h. Quench the reaction with aq. NH4Cl and concentrate in vacuo. Triturate the residue in 30% MeOH/DCM, filter, and concentrate the filtrate in vacuo to an oil. Addition of H2O gives a precipitate. Filter the solid, wash with H2O and ether, and dry to give a residue containing impure product. Extract the aqueous filtrate with 1:1 EtOAc/n-butanol (4×), wash with H2O (4×), and concentrate in vacuo to get more impure product. Purify both crops by prep-TLC developing with 10% MeOH/DCM with 1% HOAc. Further purify the desired band by the same method developing with 50% MeOH/DCM to give desired product 2-(2-methyl-pyridin-4-yl)-thiazole-5-carboxylic acid as a resin (8 mg, 0.036 mmol). MS, electrospray (M+H) 221.5, rt 0.51 min.

Workup

  1. customBubble argon
  2. customQuench
  3. customthe reaction with aq. NH4Cl
  4. concentrationconcentrate in vacuo
  5. customTriturate the residue in 30% MeOH/DCM
  6. filtrationfilter
  7. concentrationconcentrate the filtrate in vacuo to an oil
  8. additionAddition of H2O
  9. customgives a precipitate
  10. filtrationFilter the solid
  11. washwash with H2O and ether
  12. customdry
  13. customto give a residue
  14. additioncontaining impure product
  15. extractionExtract the aqueous filtrate with 1:1 EtOAc/n-butanol (4×)
  16. washwash with H2O (4×)
  17. concentrationconcentrate in vacuo
  18. customto get more impure product
  19. customPurify both crops
  20. customFurther purify the desired band by the same method

Sources & evidence

ORD record
ord-dfb48073626d4acb9b17c1d240851838
Source dataset
uspto-grants-2014_04
Patent number
US08697911B2

Reaction notes

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