Trifluoroacetic acid → HCID 178433739, 화합물

HRID 2282279노트

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HRID 2282279 반응식
Br[C:2]1[N:3]=[C:4]([C:20]2[C:21]([CH3:29])=[N:22][N:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=23)[S:5][C:6]=1[C:7]1[N:11]=[CH:10][N:9](COCC[Si](C)(C)C)[N:8]=1.[OH:30][CH2:31][C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1.C([O-])(O)=O.[Na+].FC(F)(F)C(O)=O>C(Cl)Cl.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].COCCOC>[CH3:29][C:21]1[C:20]([C:4]2[S:5][C:6]([C:7]3[N:11]=[CH:10][NH:9][N:8]=3)=[C:2]([C:35]3[CH:36]=[CH:37][C:32]([CH2:31][OH:30])=[CH:33][CH:34]=3)[N:3]=2)=[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][N:23]2[N:22]=1

참가 물질

8

반응물 4

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 27347064-(Hydroxymethyl)benzeneboronic acidHCID 580948524-bromo-2-(2-methylpyrazolo[1,5-a]pyridin-3-yl)-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-3-yl)thiazole

생성물 1

HCID 178433739HCID 178433739, 화합물수율 26%

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 6344Dichloromethane용매HCID 80711,2-Dimethoxyethane용매

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온도
125 °C

실험 절차

Into a microwave vial containing a mixture of 4-bromo-2-(2-methylpyrazolo[1,5-a]pyridin-3-yl)-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-3-yl)thiazole (0.030 g, 0.061 mmol) and 4-(hydroxymethyl)phenylboronic acid (0.026 g, 0.17 mmol) was added 1M aqueous NaHCO3 (0.15 mL, 0.15 mmol), [1,1′-Bis(diphenylphosphino)ferrocene]palladium(II) dichloride (0.0021 g, 0.003 mmol) and 1,2-dimethoxyethane (0.60 mL). The vial was flushed with nitrogen gas and the reaction mixture was heated at 125° C. in a Biotage Microwave reactor for 30 minutes. Upon cooling to room temperature, the reaction was concentrated in vacuo and the residue obtained was partitioned between water (2 mL) & a mixture of CHCl3/THF (4:1, 3 mL). Upon separation of the layers, the aqueous layer was extracted with additional CHCl3/THF (4:1, 3 mL), the combined layers were filtered and concentrated. The material obtained was dissolved in methylene chloride (0.75 mL) and to this solution was added trifluoroacetic acid (0.5 mL, 6.4 mmol). The resulting reaction mixture was stirred overnight at room temperature. The reaction was concentrated in vacuo, the residue re-dissolved in DMSO (1 mL), filtered and purified on Agilent A2 prep instrument mass triggered reverse phase chromatography (Waters Sunfire prep C18 10 mm 19×150 mm column). Concentration of fractions containing desired product afforded product (0.0061 g, 26% yield). LCMS: (FA) ES+ 390.

후처리

  1. additionInto a microwave vial containing
  2. customThe vial was flushed with nitrogen gas
  3. temperatureUpon cooling to room temperature
  4. concentrationthe reaction was concentrated in vacuo
  5. customthe residue obtained
  6. customwas partitioned between water (2 mL)
  7. additiona mixture of CHCl3/THF (4:1, 3 mL)
  8. customUpon separation of the layers
  9. extractionthe aqueous layer was extracted with additional CHCl3/THF (4:1, 3 mL)
  10. filtrationthe combined layers were filtered
  11. concentrationconcentrated
  12. customThe material obtained
  13. customThe resulting reaction mixture
  14. concentrationThe reaction was concentrated in vacuo
  15. dissolutionthe residue re-dissolved in DMSO (1 mL)
  16. filtrationfiltered
  17. custompurified on Agilent A2
  18. additionConcentration of fractions containing desired product

출처 및 근거

ORD 기록
ord-3ef3c7b6844b41b6b5c4ee8911f5c934
출처 데이터셋
uspto-grants-2015_09
특허 번호
US09139589B2

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