Triphenylphosphine → 3-chloro-5-[(4-methyl-2-oxo-1-{2-[1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl]ethyl}-1,2-dihydropyridin-3-yl)oxy]benzonitrile

HRID 1952358Notes

Reaction equation

HRID 1952358 reaction equation
[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[N:7]1[C:11]2=[N:12][CH:13]=[CH:14][CH:15]=[C:10]2[C:9]([CH2:16][CH2:17]O)=[N:8]1.[Cl:19][C:20]1[CH:21]=[C:22]([CH:25]=[C:26]([O:28][C:29]2[C:30](=[O:36])[NH:31][CH:32]=[CH:33][C:34]=2[CH3:35])[CH:27]=1)[C:23]#[N:24].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C(Cl)Cl>[Cl:19][C:20]1[CH:21]=[C:22]([CH:25]=[C:26]([O:28][C:29]2[C:30](=[O:36])[N:31]([CH2:17][CH2:16][C:9]3[C:10]4[C:11](=[N:12][CH:13]=[CH:14][CH:15]=4)[N:7]([CH:2]4[CH2:3][CH2:4][CH2:5][CH2:6][O:1]4)[N:8]=3)[CH:32]=[CH:33][C:34]=2[CH3:35])[CH:27]=1)[C:23]#[N:24]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 685070442-[1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl]ethanolHCID 685131983-Chloro-5-[(4-methyl-2-oxo-1,2-dihydropyridin-3-yl)oxy]benzonitrile

Product 1

HCID 685097253-chloro-5-[(4-methyl-2-oxo-1-{2-[1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl]ethyl}-1,2-dihydropyridin-3-yl)oxy]benzonitrile

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-[1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl]ethanol (14.6 mg, 0.059 mmol) in CH2Cl2 (400 ul) was added 3-chloro-5-[(4-methyl-2-oxo-1,2-dihydropyridin-3-yl)oxy]benzonitrile (15.4 mg, 0.059 mmol), and the resulting mixture was stirred over an ice bath for 5 minutes. The mixture was then treated with triphenylphosphine (30.9 mg, 0.118 mmol) and then diisopropylyazodicarboxylate (13 ul, 0.068 mmol) and stirred over an ice bath for 10 minutes and then at 25° C. for 30 minutes. LC-MS showed the reaction was not complete, and so the mixture was re-cooled over an ice bath and treated with additional diisopropylazodicarboxylate (10 μL, 0.052 mmol). This mixture was stirred over an ice bath for 5 minutes and then stirred at 25° C. for 20 minutes to give a 3:2 mixture of 0 to N alkylation. After this time, the reaction was quenched with MeOH (1 mL) and purified on Gilson LC using a Luna reverse phase column (10μ, C18, 250×21.2 mm) and eluting with a gradient of 5-95% ACN/water (0.5% TFA). The desired fractions were combined and evap in vacuo to give the title compound. LRMS (M+1): 489.9/405.9.

Workup

  1. stirringstirred over an ice bath for 10 minutes
  2. waitat 25° C. for 30 minutes
  3. temperatureso the mixture was re-cooled over an ice bath
  4. stirringThis mixture was stirred over an ice bath for 5 minutes
  5. stirringstirred at 25° C. for 20 minutes
  6. customto give
  7. additiona 3:2 mixture of 0 to N alkylation
  8. customAfter this time, the reaction was quenched with MeOH (1 mL)
  9. custompurified on Gilson LC
  10. washeluting with a gradient of 5-95% ACN/water (0.5% TFA)

Sources & evidence

ORD record
ord-aa111ba88bb34aab8f416d49920c774f
Source dataset
uspto-grants-2013_03
Patent number
US08404856B2

Reaction notes

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