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

HRID 1504861Notes

Reaction equation

HRID 1504861 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[C:15]([CH3:17])[CH:14]=[C:13]([CH3:18])[N:12]=2)[C:5]([C:8]#[N:9])=[N:6][CH:7]=1.[NH2:19][CH2:20][CH:21]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])[C:22]([NH:24][CH3:25])=[O:23].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:8]([C:5]1[N:6]=[CH:7][C:2]([NH:19][CH2:20][CH:21]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:31])([CH3:30])[CH3:32])[C:22]([NH:24][CH3:25])=[O:23])=[CH:3][C:4]=1[NH:10][C:11]1[CH:16]=[C:15]([CH3:17])[CH:14]=[C:13]([CH3:18])[N:12]=1)#[N:9]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 867316505-Bromo-3-[(4,6-dimethylpyridin-2-yl)amino]pyridine-2-carbonitrileHCID 86731730Tert-butyl 3-amino-1-(methylamino)-1-oxopropan-2-ylcarbamate

Product 1

HCID 86731729Tert-butyl [3-({6-cyano-5-[(4,6-dimethylpyridin-2-yl)amino]pyridin-3-yl}amino)-1-(methylamino)-1-oxopropan-2-yl]carbamate

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

Dioxane (1.65 ml) was added to a nitrogen purged flask containing 5-bromo-3-[(4,6-dimethylpyridin-2-yl)amino]pyridine-2-carbonitrile (PrepEx 1.4) (100 mg, 0.330 mmol), tert-butyl 3-amino-1-(methylamino)-1-oxopropan-2-ylcarbamate (72 mg, 0.33 mmol), Xantphos (19 mg, 0.033 mmol), Pd2(dba)3 (24 mg, 0.026 mmol) and cesium carbonate (215 mg, 0.660 mmol). Nitrogen was bubbled through the reaction mixture for 5 minutes. The reaction vessel was then sealed and heated at 100° C. for 2 hours. The reaction mixture was cooled to room temperature, filtered through CELITE, and the filter cake was washed with ethyl acetate (10 mL). The filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography (0-5% methanol/ethyl acetate, linear gradient) to afford tert-butyl [3-({6-cyano-5-[(4,6-dimethylpyridin-2-yl)amino]pyridin-3-yl}amino)-1-(methylamino)-1-oxopropan-2-yl]carbamate. MS ESI calc'd. for C22H30N7O3 [M+H]+ 440. found 440.

Workup

  1. customNitrogen was bubbled through the reaction mixture for 5 minutes
  2. customThe reaction vessel was then sealed
  3. temperatureThe reaction mixture was cooled to room temperature
  4. filtrationfiltered through CELITE
  5. washthe filter cake was washed with ethyl acetate (10 mL)
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography (0-5% methanol/ethyl acetate, linear gradient)

Sources & evidence

ORD record
ord-f735f951f1944937a0fae4e1847b836a
Source dataset
uspto-grants-2015_12
Patent number
US09216173B2

Reaction notes

Loading…