Diisopropylethylamine → N-(5-((2-Chlorobenzyl)thio)-4-(trifluoromethyl)thiazol-2-yl)picolinamide

HRID 716622Notes

Reaction equation

HRID 716622 reaction equation
Br[C:2]1[S:6][C:5]([NH:7][C:8](=[O:15])[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=2)=[N:4][C:3]=1[C:16]([F:19])([F:18])[F:17].C(N(C(C)C)CC)(C)C.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[Cl:71][C:72]1[CH:77]=[CH:76][CH:75]=[CH:74][C:73]=1[CH2:78][SH:79]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[Cl:71][C:72]1[CH:77]=[CH:76][CH:75]=[CH:74][C:73]=1[CH2:78][S:79][C:2]1[S:6][C:5]([NH:7][C:8](=[O:15])[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=2)=[N:4][C:3]=1[C:16]([F:19])([F:18])[F:17]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 5807592-Chlorobenzyl mercaptanHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86688229N-(5-Bromo-4-(trifluoromethyl)thiazol-2-yl)picolinamide

Product 1

HCID 86688230N-(5-((2-Chlorobenzyl)thio)-4-(trifluoromethyl)thiazol-2-yl)picolinamide

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

In a 5 mL microwave vial was charged with N-(5-bromo-4-(trifluoromethyl)thiazol-2-yl)picolinamide (0.06 g, 0.2 mmol), diisopropylethylamine (59 μL, 0.34 mmol), Pd2(dba)3 (0.0048 g, 0.0085 mmol), Xantphos (0.0099 g, 0.017 mmol), 1,4-dioxane (0.6 mL) and 2-chlorophenylmethanethiol (22 μL, 0.17 mmol). The reaction mixture was purged with argon for 5 min; the vial was capped and heated at 100° C. for 15 h. the reaction mixture was cooled to room temperature, diluted with ethyl acetate (5 mL), filtered, washing with ethyl acetate (10 mL) and the filtrate was concentrated under vacuum. The residue was purified by column chromatography eluting with ethyl acetate/hexanes 0 to 30% to give the product.

Workup

  1. customThe reaction mixture was purged with argon for 5 min
  2. customthe vial was capped
  3. temperaturewas cooled to room temperature
  4. additiondiluted with ethyl acetate (5 mL)
  5. filtrationfiltered
  6. washwashing with ethyl acetate (10 mL)
  7. concentrationthe filtrate was concentrated under vacuum
  8. customThe residue was purified by column chromatography
  9. washeluting with ethyl acetate/hexanes 0 to 30%
  10. customto give the product

Sources & evidence

ORD record
ord-295d2d36d9954102b79748799afa703b
Source dataset
uspto-grants-2015_11
Patent number
US09192603B2

Reaction notes

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