3-Chloroaniline → HCID 86700762, compound

HRID 2174419Notes

Reaction equation

HRID 2174419 reaction equation
Br[C:2]1[N:7]=[CH:6][C:5]([C@@H:8]2[CH2:10][C@H:9]2[NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[CH:4][CH:3]=1.[Cl:19][C:20]1[CH:21]=[C:22]([CH:24]=[CH:25][CH:26]=1)[NH2:23].CC(C)([O-])C.[Na+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:19][C:20]1[CH:21]=[C:22]([NH:23][C:2]2[N:7]=[CH:6][C:5]([C@@H:8]3[CH2:10][C@H:9]3[NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[CH:4][CH:3]=2)[CH:24]=[CH:25][CH:26]=1

Participants

6

Reactant 3

HCID 79323-ChloroanilineHCID 23676156Sodium t-butoxideHCID 86691195tert-butyl ((1R,2S)-2-(6-bromopyridin-3-yl)cyclopropyl)carbamate2×

Product 1

HCID 86700762HCID 86700762, compoundYield 63%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A solution of tert-butyl (trans)-2-(6-bromopyridin-3-yl)cyclopropylcarbamate (Intermediate E, 250 mg, 0.798 mmol), 3-chloroaniline (122 mg, 0.958 mmol), Sodium tert-butoxide (115 mg, 1.198 mmol) in 1,4-dioxane (5 mL) was degassed for 30 min, tris(dibenzylidene acetone)dipalladium(0) (36 mg, 0.039 mmol) and 4,5-Bis(diphenyl phosphino)-9,0-dimethyl xanthene (138 mg, 0.39 mmol) was added and heated for 4 h at 80° C. After completion, the solvent was evaporated; the residue was poured into ice cold water (10 mL) and extracted with EtOAc (2×20 mL). The combined extracts were washed with water (10 mL), brine (10 mL), dried over anhydrous Na2SO4, filtered and evaporated. The crude residue was purified by flash chromatography to give tert-butyl (trans)-2-(6-(3-chlorophenylamino)pyridin-3-yl)cyclopropylcarbamate (180 mg, 63%) as white solid.

Workup

  1. customAfter completion, the solvent was evaporated
  2. additionthe residue was poured into ice cold water (10 mL)
  3. extractionextracted with EtOAc (2×20 mL)
  4. washThe combined extracts were washed with water (10 mL), brine (10 mL)
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe crude residue was purified by flash chromatography

Sources & evidence

ORD record
ord-97fa78c5c0634947ae0f7a3cd1ca349e
Source dataset
uspto-grants-2015_06
Patent number
US09061966B2

Reaction notes

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