Sodium Iodide → 1,1-Dimethylethyl 4-{[5'-({[(3-{[{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}(methyl)amino]methyl}phenyl)carbonyl]amino}methyl)-2'-fluoro-3-biphenylyl]methyl}-1-piperazinecarboxylate

HRID 564512Notes

Reaction equation

HRID 564512 reaction equation
[CH2:1]([N:3]1[C:7]2[N:8]=[C:9]([CH2:22][CH3:23])[C:10]([CH2:19][NH:20][CH3:21])=[C:11]([NH:12][CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)[C:6]=2[CH:5]=[N:4]1)[CH3:2].Cl[CH2:25][C:26]1[CH:27]=[C:28]([C:32]([NH:34][CH2:35][C:36]2[CH:37]=[CH:38][C:39]([F:62])=[C:40]([C:42]3[CH:47]=[CH:46][CH:45]=[C:44]([CH2:48][N:49]4[CH2:54][CH2:53][N:52]([C:55]([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56])[CH2:51][CH2:50]4)[CH:43]=3)[CH:41]=2)=[O:33])[CH:29]=[CH:30][CH:31]=1.C([O-])([O-])=O.[K+].[K+].[Na+].[I-]>CN(C=O)C.CCOC(C)=O>[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:22][CH3:23])=[C:10]([CH2:19][N:20]([CH2:25][C:26]3[CH:27]=[C:28]([C:32]([NH:34][CH2:35][C:36]4[CH:37]=[CH:38][C:39]([F:62])=[C:40]([C:42]5[CH:47]=[CH:46][CH:45]=[C:44]([CH2:48][N:49]6[CH2:50][CH2:51][N:52]([C:55]([O:57][C:58]([CH3:60])([CH3:59])[CH3:61])=[O:56])[CH2:53][CH2:54]6)[CH:43]=5)[CH:41]=4)=[O:33])[CH:29]=[CH:30][CH:31]=3)[CH3:21])[C:11]([NH:12][CH:13]3[CH2:14][CH2:15][O:16][CH2:17][CH2:18]3)=[C:6]2[CH:5]=[N:4]1)[CH3:2]

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 578133271,6-Diethyl-5-[(methylamino)methyl]-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-amineHCID 578133491,1-Dimethylethyl 4-({5'-[({[3-(chloromethyl)phenyl]carbonyl}amino)methyl]-2'-fluoro-3-biphenylyl}methyl)-1-piperazinecarboxylate

Product 1

HCID 578134351,1-Dimethylethyl 4-{[5'-({[(3-{[{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}(methyl)amino]methyl}phenyl)carbonyl]amino}methyl)-2'-fluoro-3-biphenylyl]methyl}-1-piperazinecarboxylateYield 49%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1,6-diethyl-5-[(methylamino)methyl]-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-amine (0.0432 g, 0.136 mmol) in DMF (1.0 mL) was added 1,1-dimethylethyl 4-({5′-[({[3-(chloromethyl)phenyl]carbonyl}amino)methyl]-2′-fluoro-3-biphenylyl}methyl)-1-piperazinecarboxylate (0.075 g, 0.136 mmol), and K2CO3 (0.0188 g, 0.136 mmol). This mixture was stirred at room temperature for 18 h after which was added NaI (0.0204 g, 0.136 mmol) and stirring continued for another 25 h. Then the mixture was diluted with EtOAc (5 mL), washed with H2O (2×3 mL), brine (3 mL), concentrated, and purified by CombiFlash chromatograph to afford the title compound 0.055 g (49%). LC-MS m/z 833 (M+H)+.

Workup

  1. stirringstirring
  2. waitcontinued for another 25 h
  3. washwashed with H2O (2×3 mL), brine (3 mL)
  4. concentrationconcentrated
  5. custompurified by CombiFlash chromatograph

Sources & evidence

ORD record
ord-4a57c002ef8548fcbb5971577524ebcc
Source dataset
uspto-grants-2011_11
Patent number
US08067408B2

Reaction notes

Loading…