Sodium Bicarbonate → HCID 44547092, compound

HRID 237410Notes

Reaction equation

HRID 237410 reaction equation
Br[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([CH:11]3[C:20]([C:21]#[N:22])=[C:19]([CH3:23])[N:18]4[C:13]([CH2:14][O:15][CH2:16][CH2:17]4)=[C:12]3[C:24]#[N:25])[CH:9]=2)[NH:4][N:3]=1.[F:26][C:27]1[N:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1.C(=O)(O)[O-].[Na+]>O1CCOCC1.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>[F:26][C:27]1[N:32]=[CH:31][C:30]([C:2]2[C:10]3[C:5](=[CH:6][CH:7]=[C:8]([CH:11]4[C:20]([C:21]#[N:22])=[C:19]([CH3:23])[N:18]5[C:13]([CH2:14][O:15][CH2:16][CH2:17]5)=[C:12]4[C:24]#[N:25])[CH:9]=3)[NH:4][N:3]=2)=[CH:29][CH:28]=1

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 2783397(6-Fluoropyridin-3-yl)boronic acidHCID 178428407HCID 178428407, compound

Product 1

HCID 44547092HCID 44547092, compoundYield 49.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

To a degassed solution of 125 mg (0.315 mmol) 8-(3-bromo-1H-indazol-5-yl)-6-methyl-1,3,4,8-tetrahydropyrido[2,1-c][1,4]oxazine-7,9-dicarbonitrile (Example 12A) and 53.3 mg (0.379 mmol) (6-fluoropyridin-3-yl)boronic acid in anhydrous 1,4-dioxane (2.2 ml) were added under inert gas atmosphere 36.5 mg (0.032 mmol) tetrakis(triphenylphosphine)palladium(0) and aqueous sodium bicarbonate solution (2 M, 0.56 ml). The resulting mixture was stirred at 140° C. for 70 min under microwave conditions. After cooling to room temperature and concentration under reduced pressure, the remaining solid was dissolved in ethyl acetate (20 ml). The solution was subsequently 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 95:5 v/v) to yield the title compound as a white solid (64 mg, 49% of th.).

Workup

  1. temperatureAfter cooling to room temperature
  2. concentrationconcentration under reduced pressure
  3. dissolutionthe remaining solid was dissolved in ethyl acetate (20 ml)
  4. washThe solution was subsequently 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 95:5 v/v)

Sources & evidence

ORD record
ord-f545e3c29a40467e9b8d6408d3a29c2d
Source dataset
uspto-grants-2014_02
Patent number
US08642595B2

Reaction notes

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