Cesium carbonate → tert-butyl [(2S)-1-({6-cyano-5-[(4,6-dimethylpyridin-2-yl)amino]pyridin-3-yl}amino)propan-2-yl]carbamate

HRID 1504858Notes

Reaction equation

HRID 1504858 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:10][CH2:11][C@@H:12]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH3:13])[CH:5]=[N:6][C:7]=1[C:8]#[N:9].[NH2:22][C:23]1[CH:28]=[C:27]([CH3:29])[CH:26]=[C:25]([CH3:30])[N:24]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1>[C:8]([C:7]1[N:6]=[CH:5][C:4]([NH:10][CH2:11][C@@H:12]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH3:13])=[CH:3][C:2]=1[NH:22][C:23]1[CH:28]=[C:27]([CH3:29])[CH:26]=[C:25]([CH3:30])[N:24]=1)#[N:9]

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 215072-Amino-4,6-dimethylpyridineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86731723tert-butyl {(2S)-1-[(5-bromo-6-cyanopyridin-3-yl)amino]propan-2-yl}carbamate

Product 1

HCID 86731724tert-butyl [(2S)-1-({6-cyano-5-[(4,6-dimethylpyridin-2-yl)amino]pyridin-3-yl}amino)propan-2-yl]carbamate

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a flask were added tert-butyl {(2S)-1-[(5-bromo-6-cyanopyridin-3-yl)amino]propan-2-yl}carbamate (200 mg, 0.56 mmol), 2-amino-4,6-dimethylpyridine (103 mg, 0.844 mmol), tris(dibenzylideneacetone)dipalladium(0)-dichloromethane complex (52 mg, 0.051 mmol), Xantphos (65 mg, 0.11 mmol), and cesium carbonate (367 mg, 1.13 mmol). 1,4-Dioxane (3 mL) was then added and nitrogen was bubbled into the reaction for 5 minutes. The reaction mixture was then stirred at 80° C. for 16 hours. The reaction mixture was cooled to room temperature and diluted with ethyl acetate. The mixture was washed with saturated aqueous ammonium chloride, and the organics were separated, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by chromatography on silica gel to afford tert-butyl [(2S)-1-({6-cyano-5-[(4,6-dimethylpyridin-2-yl)-amino]pyridin-3-yl}amino)propan-2-yl]carbamate. MS ESI calc'd. for C21H29N6O2 [M+H]+ 397. found 397.

Workup

  1. customnitrogen was bubbled into the reaction for 5 minutes
  2. temperatureThe reaction mixture was cooled to room temperature
  3. additiondiluted with ethyl acetate
  4. washThe mixture was washed with saturated aqueous ammonium chloride
  5. customthe organics were separated
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-d8062a44eec7438395157bd4f0adf1d3
Source dataset
uspto-grants-2015_12
Patent number
US09216173B2

Reaction notes

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