Potassium Carbonate → 3-chloro-5-{[1-({1-(4-methoxybenzyl)-6-[(4-methoxybenzyl)amino]-1H-pyrazolo[3,4-b]pyridin-3-yl}methyl)-2-oxo-4-(trifluoromethyl)-1,2-dihydropyridin-3-yl]oxy}benzonitrile

HRID 1952365Notes

Reaction equation

HRID 1952365 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([O:10][C:11]2[C:12](=[O:21])[NH:13][CH:14]=[CH:15][C:16]=2[C:17]([F:20])([F:19])[F:18])[CH:9]=1)[C:5]#[N:6].C(=O)([O-])[O-].[K+].[K+].Cl[CH2:29][C:30]1[C:38]2[C:33](=[N:34][C:35]([NH:39][CH2:40][C:41]3[CH:46]=[CH:45][C:44]([O:47][CH3:48])=[CH:43][CH:42]=3)=[CH:36][CH:37]=2)[N:32]([CH2:49][C:50]2[CH:55]=[CH:54][C:53]([O:56][CH3:57])=[CH:52][CH:51]=2)[N:31]=1>CN(C)C=O.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([O:10][C:11]2[C:12](=[O:21])[N:13]([CH2:29][C:30]3[C:38]4[C:33](=[N:34][C:35]([NH:39][CH2:40][C:41]5[CH:42]=[CH:43][C:44]([O:47][CH3:48])=[CH:45][CH:46]=5)=[CH:36][CH:37]=4)[N:32]([CH2:49][C:50]4[CH:51]=[CH:52][C:53]([O:56][CH3:57])=[CH:54][CH:55]=4)[N:31]=3)[CH:14]=[CH:15][C:16]=2[C:17]([F:18])([F:19])[F:20])[CH:9]=1)[C:5]#[N:6]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 568336463-(Chloromethyl)-N,1-bis(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-6-amineHCID 584600483-Chloro-5-((1,2-dihydro-2-oxo-4-(trifluoromethyl)-3-pyridinyl)oxy)benzonitrile

Product 1

HCID 595297293-chloro-5-{[1-({1-(4-methoxybenzyl)-6-[(4-methoxybenzyl)amino]-1H-pyrazolo[3,4-b]pyridin-3-yl}methyl)-2-oxo-4-(trifluoromethyl)-1,2-dihydropyridin-3-yl]oxy}benzonitrile

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To 3-chloro-5-{[2-oxo-4-(trifluoromethyl)-1,2-dihydropyridin-3-yl]oxy}benzonitrile (3C, 0.150 g, 0.477 mmol) and potassium carbonate (0.066 g, 0.477 mmol) suspended in dimethylformamide (1 mL) was added 3-(chloromethyl)-N,1-bis(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-6-amine (0.202 g, 0.477 mmol) as a solution in dimethyl formamide (1 mL). The reaction mixture was allowed to stir at room temperature. After 16 hours, the reaction mixture was diluted with ethyl acetate (50 mL), washed with brine (3×25 mL), dried (MgSO4), filtered and the solvent was evaporated under reduced pressure. The resulting residue was adsorbed onto silica gel and purified by column chromatography on a pre-packed silica gel Redi Sep 40 gram column, eluting with 0-5% methanol in CH2Cl2 to afford the title compound. 1H NMR (DMSO-d6) δ 7.91 (d, J=7.0 Hz, 1H), 7.76-7.74 (m, 1H), 7.72-7.68 (m, 1H), 7.58-7.56 (m, 1H), 7.54 (d, J=8.6 Hz, 1H), 7.49-7.47 (m, 1H), 7.26 (d, J=8.6 Hz, 2H), 7.13 (d, J=8.6 Hz, 2H), 6.83 (d, J=8.6 Hz, 2H), 6.76 (d, J=8.6 Hz, 2H), 6.59 (d, J=7.2 Hz, 1H), 6.40 (d, J=8.9 Hz, 1H), 5.30 (s, 2H), 5.28 (s, 2H), 4.50-4.46 (m, 2H), 3.71 (s, 3H), 3.69 (s, 3H). LRMS (M+1)=700.6.

Workup

  1. washwashed with brine (3×25 mL)
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. customthe solvent was evaporated under reduced pressure
  5. custompurified by column chromatography on a pre-packed silica gel Redi Sep 40 gram column
  6. washeluting with 0-5% methanol in CH2Cl2

Sources & evidence

ORD record
ord-e30d1d3d2582446886d4a61000b1ea75
Source dataset
uspto-grants-2013_03
Patent number
US08404856B2

Reaction notes

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