Trifluoroacetic acid → HCID 178433739、化合物

HRID 1530115ノート

反応式

HRID 1530115 の反応式
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

参加物

8

反応物 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

生成物 1

HCID 178433739HCID 178433739、化合物収率 26%

試薬・触媒・溶媒 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 6344Dichloromethane溶媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
125 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-b2db4cf5ca1e4a19aac17e0223a550dc
出典データセット
uspto-grants-2015_07
特許番号
US09090601B2

反応ノート

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