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

HRID 1522606Notes

Reaction equation

HRID 1522606 reaction equation
I[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[N:9][N:10]([CH:11]([CH3:13])[CH3:12])[C:3]=12.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:56][C:57]1[C:58]([C:64]2[CH:69]=[C:68]([NH2:70])[CH:67]=[CH:66][N:65]=2)=[N:59][C:60]([CH3:63])=[CH:61][CH:62]=1.CC([O-])(C)C.[Na+]>O1CCOCC1.O.C(#N)C.O.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:56][C:57]1[C:58]([C:64]2[CH:69]=[C:68]([NH:70][C:2]3[CH:7]=[CH:6][N:5]=[C:4]4[CH:8]=[N:9][N:10]([CH:11]([CH3:13])[CH3:12])[C:3]=34)[CH:67]=[CH:66][N:65]=2)=[N:59][C:60]([CH3:63])=[CH:61][CH:62]=1

Participants

9

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 674704007-iodo-1-isopropyl-1H-pyrazolo[4,3-b]pyridine

Product 1

HCID 54670416N-(3'-fluoro-6'-methyl-2,2'-bipyridin-4-yl)-1-isopropyl-1H-pyrazolo[4,3-b]pyridin-7-amineYield 23%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Conditions

Temperature
120 °C

Procedure

7-Iodo-1-isopropyl-1H-pyrazolo[4,3-b]pyridine (24 mg, 0.084 mmol), Tris(dibenzylideneacetone)dipalladium(0) (2.82 mg, 3.08 μmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (17.80 mg, 0.031 mmol), 3′-fluoro-6′-methyl-2,2′-bipyridin-4-amine (25 mg, 0.123 mmol) and sodium 2-methylpropan-2-olate (35.5 mg, 0.369 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 Phenomenex Gemini Prep 5 μm C18, 75×30 mm column eluting with a gradient of 20-50% 10 mmol NH4HCO3 in 20/80 (v/v) water/acetonitrile in 10 mmol NH4HCO3 in water to afford N-(3′-fluoro-6′-methyl-2,2′-bipyridin-4-yl)-1-isopropyl-1H-pyrazolo[4,3-b]pyridin-7-amine (7 mg, 15.70% yield). 1H NMR (400 MHz, METHANOL-d4) δ ppm 1.48 (s, 6H) 2.61 (s, 3H) 5.08-5.21 (m, 1H) 7.03 (dd, J=5.81, 2.02 Hz, 1H) 7.36-7.47 (m, 2H) 7.49 (s, 1H) 7.62-7.71 (m, 1H) 8.30 (s, 1H) 8.42 (d, J=6.06 Hz, 1H) 8.51 (d, J=4.80 Hz, 1H). MS [M+H] found 363.4.

Workup

  1. temperaturecooled
  2. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-00434c38ed294dd68b4d86beb2afd8dc
Source dataset
uspto-grants-2015_07
Patent number
US09073918B2

Reaction notes

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