Cesium carbonate → HCID 59405009, compound

HRID 1672201Notes

Reaction equation

HRID 1672201 reaction equation
Cl[C:2]1[CH:3]=[C:4]([NH:12][C:13]2[N:14]=[CH:15][C:16]3[CH2:17][C:18](=[O:32])[NH:19][C:20]4[CH:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[CH:24][C:21]=4[C:22]=3[N:23]=2)[C:5]([C:8]([F:11])([F:10])[F:9])=[N:6][CH:7]=1.[CH2:33]([N:36]([CH3:38])[CH3:37])[C:34]#[CH:35].C(=O)([O-])[O-].[Cs+].[Cs+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>CN(C=O)C.CC#N.CC#N.Cl[Pd]Cl>[CH3:37][N:36]([CH3:38])[CH2:33][C:34]#[C:35][C:2]1[CH:3]=[C:4]([NH:12][C:13]2[N:14]=[CH:15][C:16]3[CH2:17][C:18](=[O:32])[NH:19][C:20]4[CH:27]=[C:26]([C:28]([F:31])([F:29])[F:30])[CH:25]=[CH:24][C:21]=4[C:22]=3[N:23]=2)[C:5]([C:8]([F:11])([F:9])[F:10])=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 81643N,N-DimethylpropargylamineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 59405022HCID 59405022, compound

Product 1

HCID 59405009HCID 59405009, compoundYield 67.3%

Reagents, catalysts & solvents 2

HCID 6093782Bis(acetonitrile)dichloropalladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 2-{[5-chloro-2-(trifluoromethyl)pyridin-3-yl]amino}-9-(trifluoromethyl)-5,7-dihydro-6H-pyrimido[5,4-d][1]benzazepin-6-one (0.058 g, 0.12 mmol), propargyl(dimethylamine) (0.016 mL, 0.15 mmol) and cesium carbonate (0.080 g, 0.25 mmol) in DMF (0.60 ml) was degassed for 15 min with argon. To the suspension were added bis(acetonitrile)palladium(II)chloride (0,0020 g, 0.0061 mmol) and Xphos (0.0076 g, 0.016 mmol). The suspension was purged three times with nitrogen and was then allowed to stir at 150° C. for 48 h. The mixture was filtered through celite and the filtrate was concentrated. The residue was purified by column chromatography to give 2-{[5-[3-(dimethylamino)prop-1-yn-1-yl]-2-(trifluoromethyl)pyridin-3-yl]amino}-9-(trifluoromethyl)-5,7-dihydro-6H-pyrimido[5,4-d][1]benzazepin-6-one (0.042g, 66%) as a solid.

Workup

  1. customwas degassed for 15 min with argon
  2. customThe suspension was purged three times with nitrogen
  3. filtrationThe mixture was filtered through celite
  4. concentrationthe filtrate was concentrated
  5. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-bfd260e07d5e4d928daad08ee5bf9812
Source dataset
uspto-grants-2011_08
Patent number
US07998952B2

Reaction notes

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