2-Methyl-3-butyn-2-ol → HCID 25226754, compound

HRID 1802481Notes

Reaction equation

HRID 1802481 reaction equation
Br[C:2]1[CH:30]=[CH:29][C:5]2[N:6]=[C:7]([NH:15][C:16]3[C:21]([Cl:22])=[CH:20][C:19]([C:23]4[NH:27][N:26]=[CH:25][CH:24]=4)=[CH:18][C:17]=3[Cl:28])[C:8]3[CH:9]=[CH:10][NH:11][C:12](=[O:14])[C:13]=3[C:4]=2[CH:3]=1.C(N(CC)CC)C.[CH3:38][C:39]([OH:43])([C:41]#[CH:42])[CH3:40]>CN(C=O)C.C(OCC)(=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.[Cu]I>[Cl:28][C:17]1[CH:18]=[C:19]([C:23]2[NH:27][N:26]=[CH:25][CH:24]=2)[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:42]#[C:41][C:39]([OH:43])([CH3:40])[CH3:38])[CH:30]=[CH:29][C:5]=2[N:6]=1

Participants

8

Reactant 3

HCID 82582-Methyl-3-butyn-2-olHCID 8471TriethylamineHCID 59435999HCID 59435999, compound

Product 1

HCID 25226754HCID 25226754, compound

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
75 °C

Procedure

A solution of 9-bromo-5-{[2,6-dichloro-4-(1H-pyrazol-5-yl)phenyl]amino}benzo[c]-2,6-naphthyridin-1(2H)-one (125 mg, 0.25 mmol) in DMF (3 mL) was degassed with nitrogen. Triethylamine (0.07 ml, 0.50 mmol), 2-methylbut-3-yn-2-ol (42.0 mg, 0.499 mmol), Pd(Ph3P)4 (28.8 mg, 0.025 mmol) and copper(I) iodide (9.50 mg, 0.050 mmol) were added and the reaction was heated to 75° C. for 16 h. After cooling to room temperature, the reaction was diluted with ethyl acetate and extracted with water. The organic layer was dried with sodium sulfate, filtered and concentrated under reduced pressure. The residue was dissolved in THF/MeOH, filtered and purified by reverse phase HPLC to afford the title compound.

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionextracted with water
  3. dry with materialThe organic layer was dried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe residue was dissolved in THF/MeOH
  7. filtrationfiltered
  8. custompurified by reverse phase HPLC

Sources & evidence

ORD record
ord-ebe2f557d24947f88f0c2104b980e793
Source dataset
uspto-grants-2013_01
Patent number
US08349865B2

Reaction notes

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