Cesium carbonate → Tert-butyl {1-(acetylamino)-3-[(6-{[bis(4-methoxyphenyl)methyl]carbamoyl}-5-[(4,6-dimethylpyridin-2-yl)amino]pyridin-3-yl)amino]propan-2-yl}carbamate

HRID 1504866Notes

Reaction equation

HRID 1504866 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]([C:29]2[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=2)[NH:10][C:11]([C:13]2[C:18]([NH:19][C:20]3[CH:25]=[C:24]([CH3:26])[CH:23]=[C:22]([CH3:27])[N:21]=3)=[CH:17][C:16](Br)=[CH:15][N:14]=2)=[O:12])=[CH:5][CH:4]=1.[C:37]([NH:40][CH2:41][CH:42]([NH:45][C:46](=[O:52])[O:47][C:48]([CH3:51])([CH3:50])[CH3:49])[CH2:43][NH2:44])(=[O:39])[CH3:38].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+]>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].O1CCOCC1>[C:37]([NH:40][CH2:41][CH:42]([NH:45][C:46](=[O:52])[O:47][C:48]([CH3:51])([CH3:50])[CH3:49])[CH2:43][NH:44][C:16]1[CH:15]=[N:14][C:13]([C:11](=[O:12])[NH:10][CH:9]([C:29]2[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=2)[C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)=[C:18]([NH:19][C:20]2[CH:25]=[C:24]([CH3:26])[CH:23]=[C:22]([CH3:27])[N:21]=2)[CH:17]=1)(=[O:39])[CH3:38]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86731658N-[bis(4-methoxyphenyl)methyl]-5-bromo-3-[(4,6-dimethylpyridin-2-yl)amino]pyridine-2-carboxamideHCID 86731718Tert-butyl [1-(acetylamino)-3-aminopropan-2-yl]carbamate

Product 1

HCID 86731734Tert-butyl {1-(acetylamino)-3-[(6-{[bis(4-methoxyphenyl)methyl]carbamoyl}-5-[(4,6-dimethylpyridin-2-yl)amino]pyridin-3-yl)amino]propan-2-yl}carbamate

Reagents, catalysts & solvents 2

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

Conditions

Temperature
80 °C

Procedure

To a flask were added N-[bis(4-methoxyphenyl)methyl]-5-bromo-3-[(4,6-dimethylpyridin-2-yl)amino]pyridine-2-carboxamide (100 mg, 0.183 mmol) (PrepEx 1.11), tert-butyl [1-(acetylamino)-3-aminopropan-2-yl]carbamate (51 mg, 0.22 mmol), tris(dibenzylideneacetone)dipalladium(0) (17 mg, 0.018 mmol), Xantphos (21 mg, 0.037 mmol) and cesium carbonate (131 mg, 0.402 mmol). 1,4-Dioxane (1 mL) was added, and the reaction mixture was purged with nitrogen for 5 minutes. The reaction mixture was then stirred at 80° C. for 16 hours. The reaction mixture was cooled to room temperature, and then diluted with ethyl acetate and saturated aqueous ammonium chloride. 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 {1-(acetylamino)-3-[(6-{[bis(4-methoxyphenyl)methyl]carbamoyl}-5-[(4,6-dimethylpyridin-2-yl)amino]pyridin-3-yl)amino]propan-2-yl}carbamate. MS ESI calc'd for C38H48N7O6 [M+H]+ 698. found 698.

Workup

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

Sources & evidence

ORD record
ord-17cf8afe6eb449eda479deeea2d537ed
Source dataset
uspto-grants-2015_12
Patent number
US09216173B2

Reaction notes

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