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 1522602Notes

Reaction equation

HRID 1522602 reaction equation
I[C:2]1[C:3]2[C:4](=[CH:8][N:9]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=3)[N:10]=2)[N:5]=[CH:6][CH:7]=1.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.[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:2]3[C:3]4[C:4](=[CH:8][N:9]([CH2:11][C:12]5[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=5)[N:10]=4)[N:5]=[CH:6][CH:7]=3)[CH:73]=[CH:72][N:71]=2)=[N:65][C:66]([CH3:69])=[CH:67][CH:68]=1

Participants

7

Reactant 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23676156Sodium t-butoxideHCID 674695617-Iodo-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-b]pyridineHCID 674696053'-Fluoro-6'-methyl-2,2'-bipyridin-4-amine

Product 1

HCID 67469529N-(3'-fluoro-6'-methyl-2,2'-bipyridin-4-yl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-b]pyridin-7-amineYield 50.4%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
120 °C

Procedure

7-Iodo-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-b]pyridine (198 mg, 0.541 mmol), Tris(dibenzylideneacetone)dipalladium(0) (12.39 mg, 0.014 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (78 mg, 0.135 mmol), 3′-fluoro-6′-methyl-2,2′-bipyridin-4-amine (110 mg, 0.541 mmol) and sodium 2-methylpropan-2-olate (156 mg, 1.624 mmol) were combined in dioxane (5 mL). The mixture was heated at 120° C. for 2 hours then cooled and purified by preparative HPLC using a Sunfire Prep 5 μm C18, 75×30 mm column eluting with a gradient of 10-50% acetonitrile (containing 0.035% TFA) in water (containing 0.05% TFA) to afford N-(3′-fluoro-6′-methyl-2,2′-bipyridin-4-yl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-b]pyridin-7-amine (120 mg, 50.3% yield) as a yellow solid. MS [M+H] found 441.4.

Workup

  1. temperaturethen cooled
  2. custompurified by preparative HPLC
  3. washeluting with a gradient of 10-50% acetonitrile (containing 0.035% TFA) in water (containing 0.05% TFA)

Sources & evidence

ORD record
ord-d9b42269dd4541dbaac7a4345db126ae
Source dataset
uspto-grants-2015_07
Patent number
US09073918B2

Reaction notes

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