(S)-tert-butyl 1-(3-bromopyridin-2-yl)-2-(3,5-difluorophenyl)ethylcarbamate → (S)-tert-butyl (1-(3-(4-chloro-1-methyl-3-(methylsulfonamido)-1H-indazol-7-yl)pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)carbamate

HRID 2170394노트

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HRID 2170394 반응식
Br[C:2]1[C:3]([C@@H:8]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[CH2:9][C:10]2[CH:15]=[C:14]([F:16])[CH:13]=[C:12]([F:17])[CH:11]=2)=[N:4][CH:5]=[CH:6][CH:7]=1.[Cl:26][C:27]1[CH:35]=[CH:34][C:33](B2OC(C)(C)C(C)(C)O2)=[C:32]2[C:28]=1[C:29]([NH:46][S:47]([CH3:50])(=[O:49])=[O:48])=[N:30][N:31]2[CH3:45]>O1CCOCC1.C([O-])(O)=O.[Na+].C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.Cl[Pd]Cl>[Cl:26][C:27]1[CH:35]=[CH:34][C:33]([C:2]2[C:3]([C@@H:8]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:23])([CH3:22])[CH3:24])[CH2:9][C:10]3[CH:15]=[C:14]([F:16])[CH:13]=[C:12]([F:17])[CH:11]=3)=[N:4][CH:5]=[CH:6][CH:7]=2)=[C:32]2[C:28]=1[C:29]([NH:46][S:47]([CH3:50])(=[O:49])=[O:48])=[N:30][N:31]2[CH3:45]

참가 물질

6

반응물 2

HCID 71185105(S)-tert-butyl 1-(3-bromopyridin-2-yl)-2-(3,5-difluorophenyl)ethylcarbamateHCID 90281256N-(4-Chloro-1-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazol-3-yl)methanesulfonamide

생성물 1

HCID 90290217(S)-tert-butyl (1-(3-(4-chloro-1-methyl-3-(methylsulfonamido)-1H-indazol-7-yl)pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)carbamate

시약·촉매·용매 3

HCID 11050900Dichlorobis(tricyclohexylphosphine)pallium (II)촉매HCID 312751,4-Dioxane용매HCID 516892Sodium Bicarbonate용매

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온도
150 °C

실험 절차

(S)-tert-butyl (1-(3-bromopyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)carbamate (1.0 g, 2.42 mmol), N-(4-chloro-1-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazol-3-yl)methanesulfonamide (1.12 g, 2.90 mmol), and PdCl2[P(cy)3]2 (89.0 mg, 0.121 mmol) were suspended in 1,4-dioxane (108 mL) and 1.0 M aqueous NaHCO3 (36 mL). The reaction mixture was degassed by bubbling argon for 5 minutes then sealed and heated 150° C. for 15 minutes in a microwave reactor. Upon cooling, the reaction mixture was diluted with water and extracted with three portions of EtOAc. The combined organic layers were dried over Na2SO4, filtered, concentrated in vacuo, and purified by silica gel column chromatography, eluting with 0-100% EtOAc in hexanes to give the title compound. MS (m/z) 591.72 [M+H]+.

후처리

  1. customThe reaction mixture was degassed
  2. customby bubbling argon for 5 minutes
  3. customthen sealed
  4. temperatureUpon cooling
  5. additionthe reaction mixture was diluted with water
  6. extractionextracted with three portions of EtOAc
  7. dry with materialThe combined organic layers were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. custompurified by silica gel column chromatography
  11. washeluting with 0-100% EtOAc in hexanes

출처 및 근거

ORD 기록
ord-4d0815ebb2234a5ba451ed03c30f71bf
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09050344B2

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