Hydrochloric Acid → 2-(2-methoxyethyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-2H-pyrazolo[3,4-c][1,8]naphthyridin-4-amine

HRID 549246Notes

Reaction equation

HRID 549246 reaction equation
Cl.C(OC([NH:9][C:10]1[C:15](B(O)O)=[CH:14][CH:13]=[CH:12][N:11]=1)=O)(C)(C)C.C(=O)([O-])[O-].[K+].[K+].Br[C:26]1[C:27]([C:42]#[N:43])=[N:28][N:29]([CH2:38][CH2:39][O:40][CH3:41])[C:30]=1[CH2:31][CH:32]1[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.COCCOC>[CH3:41][O:40][CH2:39][CH2:38][N:29]1[C:30]([CH2:31][CH:32]2[CH2:37][CH2:36][O:35][CH2:34][CH2:33]2)=[C:26]2[C:27]([C:42]([NH2:43])=[N:9][C:10]3[N:11]=[CH:12][CH:13]=[CH:14][C:15]=32)=[N:28]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 22135186(2-[(tert-Butoxycarbonyl)amino]pyridin-3-yl)boronic acidHCID 671576704-bromo-1-(2-methoxyethyl)-5-(tetrahydro-2H-pyran-4-ylmethyl)-1H-pyrazole-3-carbonitrile

Product 1

HCID 119505002-(2-methoxyethyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-2H-pyrazolo[3,4-c][1,8]naphthyridin-4-amineYield 7.1%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

Hydrochloric acid (10 mL of 1M) was added to a solution of 2-tert-butoxycarbonylamino-3-pyridylboronic acid (2.59 g, 10.9 mmol), and the resulting mixture was heated at 80° C. for 45 minutes and allowed to cool to room temperature. Potassium carbonate (3.60 g, 26.0 mmol) was added with stirring, and then DME (20 mL), 4-bromo-1-(2-methoxyethyl)-5-(tetrahydro-2H-pyran-4-ylmethyl)-1H-pyrazole-3-carbonitrile (1.75 g, 5.33 mmol), and dichlorobis(triphenylphosphine)palladium(II) (190 mg, 0.27 mmol) were added. The reaction was carried out as described in Part C of Example 4. The crude product was purified by automated flash chromatography (eluting with 0% to 35% CMA in chloroform) followed by recrystallization from acetonitrile (30 mL) after hot filtration. The crystals were washed with cold acetonitrile and dried overnight in a vacuum oven at 60° C. to provide 0.13 g of 2-(2-methoxyethyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-2H-pyrazolo[3,4-c][1,8]naphthyridin-4-amine as light yellow needles, mp 230-233° C.

Workup

  1. temperatureto cool to room temperature
  2. customThe crude product was purified by automated flash chromatography (eluting with 0% to 35% CMA in chloroform)
  3. customfollowed by recrystallization from acetonitrile (30 mL)
  4. filtrationafter hot filtration
  5. washThe crystals were washed with cold acetonitrile
  6. customdried overnight in a vacuum oven at 60° C.

Sources & evidence

ORD record
ord-f7897a34eca94ccebe352b365b5c789e
Source dataset
uspto-grants-2011_05
Patent number
US07943636B2

Reaction notes

Loading…