(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 2170394Notes

Reaction equation

HRID 2170394 reaction equation
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]

Participants

6

Reactant 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

Product 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

Reagents, catalysts & solvents 3

HCID 11050900Dichlorobis(tricyclohexylphosphine)pallium (II)CatalystHCID 312751,4-DioxaneSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
150 °C

Procedure

(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]+.

Workup

  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

Sources & evidence

ORD record
ord-4d0815ebb2234a5ba451ed03c30f71bf
Source dataset
uspto-grants-2015_06
Patent number
US09050344B2

Reaction notes

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