(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 2170394ノート

反応式

HRID 2170394 の反応式
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]

参加物

6

反応物 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

生成物 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

試薬・触媒・溶媒 3

HCID 11050900Dichlorobis(tricyclohexylphosphine)pallium (II)触媒HCID 312751,4-Dioxane溶媒HCID 516892Sodium Bicarbonate溶媒

反応条件

温度
150 °C

実験手順

(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]+.

後処理

  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

出典と根拠

ORDレコード
ord-4d0815ebb2234a5ba451ed03c30f71bf
出典データセット
uspto-grants-2015_06
特許番号
US09050344B2

反応ノート

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