Hydrochloric Acid → 3-(7-(3'-fluoro-5,6'-dimethyl-2,2'-bipyridin-4-ylamino)-2H-pyrazolo[4,3-b]pyridin-2-yl)propan-1-ol

HRID 1522619Notes

Reaction equation

HRID 1522619 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[C:45]2[C:46](=[CH:50][N:51]([CH2:53][CH2:54][CH2:55][O:56]C3CCCCO3)[N:52]=2)[N:47]=[CH:48][CH:49]=1.[F:63][C:64]1[C:65]([C:71]2[CH:76]=[C:75]([NH2:77])[C:74]([CH3:78])=[CH:73][N:72]=2)=[N:66][C:67]([CH3:70])=[CH:68][CH:69]=1.CC([O-])(C)C.[Na+].Cl>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:63][C:64]1[C:65]([C:71]2[CH:76]=[C:75]([NH:77][C:44]3[C:45]4[C:46](=[CH:50][N:51]([CH2:53][CH2:54][CH2:55][OH:56])[N:52]=4)[N:47]=[CH:48][CH:49]=3)[C:74]([CH3:78])=[CH:73][N:72]=2)=[N:66][C:67]([CH3:70])=[CH:68][CH:69]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23676156Sodium t-butoxideHCID 674695327-iodo-2-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-2H-pyrazolo[4,3-b]pyridineHCID 674696193'-Fluoro-5,6'-dimethyl-2,2'-bipyridin-4-amine

Product 1

HCID 674706093-(7-(3'-fluoro-5,6'-dimethyl-2,2'-bipyridin-4-ylamino)-2H-pyrazolo[4,3-b]pyridin-2-yl)propan-1-ol

Reagents, catalysts & solvents 2

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

Conditions

Temperature
120 °C

Procedure

(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (3.74 mg, 6.46 μmol), 7-iodo-2-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-2H-pyrazolo[4,3-b]pyridine (100 mg, 0.258 mmol), Pd2(dba)3 (5.91 mg, 6.46 μmol), 3′-fluoro-5,6′-dimethyl-2,2′-bipyridin-4-amine (56.1 mg, 0.258 mmol) and sodium 2-methylpropan-2-olate (74.5 mg, 0.775 mmol) were combined in dioxane (5 mL) and heated at 120° C. for 1 hour. The reaction was then cooled, concentrated, and purified by prep-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 give a residue which was combined with 1N HCl (4 mL) and stirred at room temperature for 1 hour before the solvent was removed to give the title compound as a hydrochloride salt. 1H NMR (400 MHz, METHANOL-d4) δ ppm 2.14 (t, J=6.19 Hz, 2H) 2.68 (s, 3H) 2.71 (s, 3H) 3.52 (t, J=5.94 Hz, 2H) 4.68 (t, J=6.95 Hz, 2H) 7.54 (d, J=6.57 Hz, 1H) 7.64 (dd, J=8.59, 3.54 Hz, 1H) 7.82 (dd, J=11.37, 8.59 Hz, 1H) 8.53 (s, 1H) 8.71 (d, J=6.57 Hz, 1H) 8.86 (s, 1H) 8.90 (s, 1H). MS [M+H] found 393.4.

Workup

  1. temperatureThe reaction was then cooled
  2. concentrationconcentrated
  3. custompurified
  4. washeluting with a gradient of 10-50% acetonitrile (containing 0.035% TFA) in water (containing 0.05% TFA)
  5. customto give a residue which
  6. customwas removed

Sources & evidence

ORD record
ord-5b6995257a604fc185884c92a7ffda3c
Source dataset
uspto-grants-2015_07
Patent number
US09073918B2

Reaction notes

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