1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → N-(3'-fluoro-6'-methyl-2,2'-bipyridin-4-yl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-b]pyridin-7-amine

HRID 1522634Notes

Reaction equation

HRID 1522634 reaction equation
CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.I[C:44]1[CH:49]=[CH:48][N:47]=[C:46]2[CH:50]=[N:51][N:52]([CH2:53][C:54]3[CH:59]=[CH:58][C:57]([O:60][CH3:61])=[CH:56][CH:55]=3)[C:45]=12.[F:62][C:63]1[C:64]([C:70]2[CH:75]=[C:74]([NH2:76])[CH:73]=[CH:72][N:71]=2)=[N:65][C:66]([CH3:69])=[CH:67][CH:68]=1.CC([O-])(C)C.[Na+]>O1CCOCC1.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]>[F:62][C:63]1[C:64]([C:70]2[CH:75]=[C:74]([NH:76][C:44]3[CH:49]=[CH:48][N:47]=[C:46]4[CH:50]=[N:51][N:52]([CH2:53][C:54]5[CH:59]=[CH:58][C:57]([O:60][CH3:61])=[CH:56][CH:55]=5)[C:45]=34)[CH:73]=[CH:72][N:71]=2)=[N:65][C:66]([CH3:69])=[CH:67][CH:68]=1.[F:62][C:63]1[C:64]([C:70]2[CH:75]=[C:74]([NH:76][C:44]3[C:50]4[C:46](=[CH:45][N:52]([CH2:53][C:54]5[CH:55]=[CH:56][C:57]([O:60][CH3:61])=[CH:58][CH:59]=5)[N:51]=4)[N:47]=[CH:48][CH:49]=3)[CH:73]=[CH:72][N:71]=2)=[N:65][C:66]([CH3:69])=[CH:67][CH:68]=1

Participants

8

Reactant 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23676156Sodium t-butoxideHCID 674696053'-Fluoro-6'-methyl-2,2'-bipyridin-4-amineHCID 674704207-iodo-1-(4-methoxybenzyl)-1H-pyrazolo[4,3-b]pyridine

Product 2

HCID 67469529N-(3'-fluoro-6'-methyl-2,2'-bipyridin-4-yl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-b]pyridin-7-amineHCID 67470402N-(3'-fluoro-6'-methyl-2,2'-bipyridin-4-yl)-1-(4-methoxybenzyl)-1H-pyrazolo[4,3-b]pyridin-7-amine

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (60.0 mg, 0.104 mmol), 7-iodo-1-(4-methoxybenzyl)-1H-pyrazolo[4,3-b]pyridine (757 mg, 2.073 mmol), Pd2(dba)3 (95 mg, 0.104 mmol), 3′-fluoro-6′-methyl-2,2′-bipyridin-4-amine (421 mg, 2.073 mmol) and sodium 2-methylpropan-2-olate (598 mg, 6.22 mmol) were combined in dioxane (15 mL) and the mixture was heated at 110° C. for 10 minutes and then at 70° C. over night. The reaction was then cooled and concentrated to give a residue which was loaded onto silica and purified by column chromatography eluting with MeOH in CHCL3 (0-15%) to give N-(3′-fluoro-6′-methyl-2,2′-bipyridin-4-yl)-1-(4-methoxybenzyl)-1H-pyrazolo[4,3-b]pyridin-7-amine and N-(3′-fluoro-6′-methyl-2,2′-bipyridin-4-yl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-b]pyridin-7-amine as solid. MS [M+H] found 441.2.

Workup

  1. waitat 70° C. over night
  2. temperatureThe reaction was then cooled
  3. concentrationconcentrated
  4. customto give a residue which
  5. custompurified by column chromatography
  6. washeluting with MeOH in CHCL3 (0-15%)

Sources & evidence

ORD record
ord-743d7b82b4074c3eacbb91e46dc1c5b9
Source dataset
uspto-grants-2015_07
Patent number
US09073918B2

Reaction notes

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