2-Methoxyaniline → 6-chloro-N-(2-methoxyphenyl)-1-trityl-1H-pyrazolo[4,3-c]pyridin-3-amine

HRID 590832Notes

Reaction equation

HRID 590832 reaction equation
[CH3:1][O:2][C:3]1[CH:9]=[CH:8][CH:7]=[CH:6][C:4]=1[NH2:5].[Cl:10][C:11]1[N:16]=[CH:15][C:14]2[C:17](I)=[N:18][N:19]([C:20]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:13]=2[CH:12]=1.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=C(C(C)C)C=1)C.C1C=[C-]C(CCN)=CC=1.Cl[Pd+]>[Cl:10][C:11]1[N:16]=[CH:15][C:14]2[C:17]([NH:5][C:4]3[CH:6]=[CH:7][CH:8]=[CH:9][C:3]=3[O:2][CH3:1])=[N:18][N:19]([C:20]([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=3)([C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[C:13]=2[CH:12]=1

Participants

6

Reactant 3

HCID 70002-MethoxyanilineHCID 10796Cesium carbonateHCID 895258586-Chloro-3-iodo-1-trityl-1H-pyrazolo[4,3-c]pyridine

Product 1

HCID 1182724626-chloro-N-(2-methoxyphenyl)-1-trityl-1H-pyrazolo[4,3-c]pyridin-3-amineYield 77%

Reagents, catalysts & solvents 2

HCID 54751079XPhos PalladacycleCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 2-methoxyaniline (0.18 g), 6-chloro-3-iodo-1-trityl-1H-pyrazolo[4,3-c]pyridine (0.50 g), Cs2CO3 (0.94 g), and (2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2-aminoethyl)phenyl]palladium(II) chloride (0.071 g) in toluene (6 mL) was degassed and back filled with nitrogen (3 times) before it was heated at 80° C. for overnight. The reaction was cooled and diluted with ethyl acetate (15 mL) and water (10 mL). The mixture was filtered through celite and the filtrate was separated, the organic layer was wash with with brine (10 mL), dried (MgSO4), filtered and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel eluting with EtOAc/isohexane=25% to give 6-chloro-N-(2-methoxyphenyl)-1-trityl-1H-pyrazolo[4,3-c]pyridin-3-amine (380 mg, 77% yield) as a brown solid.

Workup

  1. customwas degassed
  2. additionback filled with nitrogen (3 times) before it
  3. temperatureThe reaction was cooled
  4. additiondiluted with ethyl acetate (15 mL) and water (10 mL)
  5. filtrationThe mixture was filtered through celite
  6. customthe filtrate was separated
  7. washthe organic layer was wash with with brine (10 mL)
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. customthe solvent was evaporated under reduced pressure
  11. customThe residue was purified by column chromatography on silica gel eluting with EtOAc/isohexane=25%

Sources & evidence

ORD record
ord-ef1ed14059994a489989704e3709e597
Source dataset
uspto-grants-2016_01
Patent number
US09233979B2

Reaction notes

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