Lithium Hexamethyldisilazide → HCID 58407621, compound

HRID 1038403Notes

Reaction equation

HRID 1038403 reaction equation
Cl[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([CH:11]3[O:16][CH2:15][CH2:14][CH2:13][O:12]3)[CH:9]=2)[N:4]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[N:3]=1.[CH3:25][O:26][CH2:27][CH2:28][CH2:29][NH:30][CH3:31].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C[Si](C)(C)[N-][Si](C)(C)C.[Li+]>C1COCC1.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]>[O:12]1[CH2:13][CH2:14][CH2:15][O:16][CH:11]1[C:8]1[CH:9]=[C:10]2[C:5](=[CH:6][CH:7]=1)[N:4]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[N:3]=[C:2]2[N:30]([CH2:29][CH2:28][CH2:27][O:26][CH3:25])[CH3:31]

Participants

7

Reactant 4

HCID 2733832Lithium HexamethyldisilazideHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 125459843-Methoxy-N-methylpropan-1-amineHCID 584075883-Chloro-5-(1,3-dioxan-2-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-indazole

Product 1

HCID 58407621HCID 58407621, compoundYield 39.7%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a degassed solution of 400 mg (1.08 mmol) 3-chloro-5-(1,3-dioxan-2-yl)-1-{[2-(trimethylsilyl)-ethoxy]methyl}-1H-indazole (Example 45A) and 135 mg (1.52 mmol) 3-methoxy-N-methyl-propanamine in anhydrous THF (11 ml) were added under inert gas atmosphere 103 mg (0.22 mmol) 2-(dicyclohexylphosphino)-2′,4′,6′-triisopropyl-1,1′-biphenyl (XPhos), 50 mg (0.054 mmol) tris(dibenzylideneacetone)dipalladium(0) (Pd2dba3) and 5.42 ml (5.42 mmol) lithium hexamethyldisilazide solution (1 M in THF). The resulting mixture was stirred under reflux for 12 h. After cooling to room temperature and concentration under reduced pressure, the remaining solid was dissolved in ethyl acetate (20 ml). The solution was washed with water and with brine, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by preparative RP-HPLC (acetonitrile/water gradient, final mixture 90:10 v/v) to yield the title compound as a white solid (187 mg, 24% of th.).

Workup

  1. temperatureunder reflux for 12 h
  2. concentrationconcentration under reduced pressure
  3. dissolutionthe remaining solid was dissolved in ethyl acetate (20 ml)
  4. washThe solution was washed with water and with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by preparative RP-HPLC (acetonitrile/water gradient, final mixture 90:10 v/v)

Sources & evidence

ORD record
ord-e0666047d254482bbf8d59913c9e86c4
Source dataset
uspto-grants-2013_10
Patent number
US08551989B2

Reaction notes

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