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

HRID 1522647Notes

Reaction equation

HRID 1522647 reaction equation
IC1C=CN=C2C=NN(C)C=12.I[C:13]1[C:14]2[C:15](=[CH:19][N:20]([CH3:22])[N:21]=2)[N:16]=[CH:17][CH:18]=1.[F:23][C:24]1[C:25]([C:31]2[CH:36]=[C:35]([NH2:37])[C:34]([CH3:38])=[CH:33][N:32]=2)=[N:26][C:27]([CH3:30])=[CH:28][CH:29]=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.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:23][C:24]1[C:25]([C:31]2[CH:36]=[C:35]([NH:37][C:13]3[C:14]4[C:15](=[CH:19][N:20]([CH3:22])[N:21]=4)[N:16]=[CH:17][CH:18]=3)[C:34]([CH3:38])=[CH:33][N:32]=2)=[N:26][C:27]([CH3:30])=[CH:28][CH:29]=1

Participants

8

Reactant 5

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23676156Sodium t-butoxideHCID 674696007-iodo-2-methyl-2H-pyrazolo[4,3-b]pyridineHCID 674696193'-Fluoro-5,6'-dimethyl-2,2'-bipyridin-4-amineHCID 674704107-iodo-1-methyl-1H-pyrazolo[4,3-b]pyridine

Product 1

HCID 67469613N-(3'-fluoro-5,6'-dimethyl-2,2'-bipyridin-4-yl)-2-methyl-2H-pyrazolo[4,3-b]pyridin-7-amine

Reagents, catalysts & solvents 2

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

Conditions

Temperature
110 °C

Procedure

A mixture of 7-iodo-1-methyl-1H-pyrazolo[4,3-b]pyridine and 7-iodo-2-methyl-2H-pyrazolo[4,3-b]pyridine (162 mg, 0.625 mmol), 3′-fluoro-5,6′-dimethyl-2,2′-bipyridin-4-amine (136 mg, 0.625 mmol), tris(dibenzylideneacetone)dipalladium(0) (28.6 mg, 0.031 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (18.09 mg, 0.031 mmol) and sodium 2-methylpropan-2-olate (180 mg, 1.876 mmol) were combined in dioxane (15 mL) and heated at 110° C. for 15 minutes. The solvent was then removed in vacuo to give a residue which was purified by preparative HPLC using a Sunfire Prep 5 μm C18, 75×30 mm column eluting with a gradient of 30-35% acetonitrile (containing 10 mM NH4HCO3) in water (containing 10 mM NH4HCO3) to give N-(3′-fluoro-5,6′-dimethyl-2,2′-bipyridin-4-yl)-2-methyl-2H-pyrazolo[4,3-b]pyridin-7-amine: 1H NMR (400 MHz, METHANOL-d4) δ ppm 0.84 (s, 3H) 0.91 (s, 3H) 1.72 (br. s., 1H) 2.54 (s, 3H) 5.58 (s, 1H) 5.62 (d, J=4 Hz, 1H) 5.72 (dd, J=12, 4 Hz, 1H) 5.94 (dd, J=12, 8 Hz, 1H) 6.58 (s, 1H) 6.80 (s, 1H) 6.83 (d, J=4 Hz, 1H). Melting point 102.9-103. Fractions were combined and further purified by a second preparative HPLC using a Sunfire Prep 5 μm C18, 75×30 mm column eluting with a gradient of 15-35% acetonitrile (containing 0.035% TFA) in water (containing 0.05% TFA) to give N-(3′-fluoro-5,6′-dimethyl-2,2′-bipyridin-4-yl)-1-methyl-1H-pyrazolo[4,3-b]pyridin-7-amine as a TFA salt. 1H NMR (400 MHz, METHANOL-d4) δ ppm 0.90 (s, 3H) 0.98 (s, 3H) 1.54-1.64 (m, 1H) 2.63 (s, 3H) 5.59 (d, J=8 Hz, 1H) 5.87 (dd, J=12, 4 Hz, 1H) 6.06 (dd, J=12, 8 Hz, 1H) 6.69 (s, 1H) 6.90 (d, J=8 Hz, 1H) 7.00 (s, 1H) 7.09 (s, 1H).

Workup

  1. customThe solvent was then removed in vacuo
  2. customto give a residue which
  3. customwas purified by preparative HPLC
  4. washeluting with a gradient of 30-35% acetonitrile (containing 10 mM NH4HCO3) in water (containing 10 mM NH4HCO3)

Sources & evidence

ORD record
ord-e5b50bd825c84296946abe528ebaaa57
Source dataset
uspto-grants-2015_07
Patent number
US09073918B2

Reaction notes

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