Sodium Carbonate → HCID 68424147, compound

HRID 1802476Notes

Reaction equation

HRID 1802476 reaction equation
Br[C:2]1[CH:28]=[CH:27][C:5]2[N:6]=[C:7]([NH:15][C:16]3[C:21]([Cl:22])=[CH:20][C:19]([CH:23]([OH:25])[CH3:24])=[CH:18][C:17]=3[Cl:26])[C:8]3[CH:9]=[CH:10][NH:11][C:12](=[O:14])[C:13]=3[C:4]=2[CH:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[CH3:35][N:36]1[CH:40]=[C:39](B2OC(C)(C)C(C)(C)O2)[CH:38]=[N:37]1>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:26][C:17]1[CH:18]=[C:19]([CH:23]([OH:25])[CH3:24])[CH:20]=[C:21]([Cl:22])[C:16]=1[NH:15][C:7]1[C:8]2[CH:9]=[CH:10][NH:11][C:12](=[O:14])[C:13]=2[C:4]2[CH:3]=[C:2]([C:39]3[CH:38]=[N:37][N:36]([CH3:35])[CH:40]=3)[CH:28]=[CH:27][C:5]=2[N:6]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 59436025HCID 59436025, compound

Product 1

HCID 68424147HCID 68424147, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 9-bromo-5-{[2,6-dichloro-4-(1-hydroxyethyl)phenyl]amino}benzo[c]-2,6-naphthyridin-1(2H)-one (Examples 94 and 95, Step 3) (300 mg, 0.63 mmol) in DMF (3 mL) were added sodium carbonate (0.3 mL, 2 M) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (208 mg, 1.00 mmol), followed by tetrakis(triphenylphosphine)palladium (0) (145 mg, 0.13 mmol). The solution was degassed by bubbling nitrogen gas for 5 min. The reaction vessel was sealed and heated to 80° C. overnight. The reaction mixture was extracted with 3:1 (CHCl3/iPrOH) and water. The organic layers were combined and dried with MgSO4, filtered, and concentrated under reduced pressure. Purification with column chromatography on silica gel (100% CH2Cl2 to 70% CH2Cl2/30% MeOH) afforded 5-{[2,6-dichloro-4-(1-hydroxyethyl)phenyl]amino}-9-(1-methyl-1H-pyrazol-4-yl)benzo[c]-2,6-naphthyridin-1(2H)-one as racemates. The enantiomers were separated using a Chiralpak AD 10 mm×250 mm column with 40% iPrOH/60% Heptane with a flow rate of 10 ml/min in a 25 min run. The first enantiomer has a retention time of 8.47 min and the second enantiomer has a retention time of 11.68 min.

Workup

  1. customThe solution was degassed
  2. customby bubbling nitrogen gas for 5 min
  3. customThe reaction vessel was sealed
  4. extractionThe reaction mixture was extracted with 3:1 (CHCl3/iPrOH) and water
  5. dry with materialdried with MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customPurification with column chromatography on silica gel (100% CH2Cl2 to 70% CH2Cl2/30% MeOH)

Sources & evidence

ORD record
ord-e0a6a6c6fb3b429eaa91316b1e036455
Source dataset
uspto-grants-2013_01
Patent number
US08349865B2

Reaction notes

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