1,1-dimethylethyl (2S)-4-[(5'-{[({2-chloro-5-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)sulfonyl]-4-fluorophenyl}carbonyl)amino]methyl}-2'-fluoro-3-biphenylyl)methyl]-2-methyl-1-piperazinecarboxylate → 2-Chloro-5-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)sulfonyl]-4-fluoro-N-[(6-fluoro-3'-{[(3S)-3-methyl-1-piperazinyl]methyl}-3-biphenylyl)methyl]benzamide

HRID 564648Notes

Reaction equation

HRID 564648 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([S:9]([NH:12][CH2:13][C:14]2[C:15]([NH:27][CH:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)=[C:16]3[CH:24]=[N:23][N:22]([CH2:25][CH3:26])[C:17]3=[N:18][C:19]=2[CH2:20][CH3:21])(=[O:11])=[O:10])=[CH:4][C:3]=1[C:34]([NH:36][CH2:37][C:38]1[CH:39]=[CH:40][C:41]([F:65])=[C:42]([C:44]2[CH:49]=[CH:48][CH:47]=[C:46]([CH2:50][N:51]3[CH2:56][CH2:55][N:54](C(OC(C)(C)C)=O)[C@@H:53]([CH3:64])[CH2:52]3)[CH:45]=2)[CH:43]=1)=[O:35]>O1CCOCC1.CO.Cl>[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([S:9]([NH:12][CH2:13][C:14]2[C:15]([NH:27][CH:28]3[CH2:29][CH2:30][O:31][CH2:32][CH2:33]3)=[C:16]3[CH:24]=[N:23][N:22]([CH2:25][CH3:26])[C:17]3=[N:18][C:19]=2[CH2:20][CH3:21])(=[O:11])=[O:10])=[CH:4][C:3]=1[C:34]([NH:36][CH2:37][C:38]1[CH:43]=[C:42]([C:44]2[CH:49]=[CH:48][CH:47]=[C:46]([CH2:50][N:51]3[CH2:56][CH2:55][NH:54][C@@H:53]([CH3:64])[CH2:52]3)[CH:45]=2)[C:41]([F:65])=[CH:40][CH:39]=1)=[O:35]

Participants

4

Reactant 1

HCID 866332011,1-dimethylethyl (2S)-4-[(5'-{[({2-chloro-5-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)sulfonyl]-4-fluorophenyl}carbonyl)amino]methyl}-2'-fluoro-3-biphenylyl)methyl]-2-methyl-1-piperazinecarboxylate

Product 1

HCID 578132752-Chloro-5-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)sulfonyl]-4-fluoro-N-[(6-fluoro-3'-{[(3S)-3-methyl-1-piperazinyl]methyl}-3-biphenylyl)methyl]benzamideYield 75.4%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidCatalystHCID 21966525Dioxane MethanolSolvent

Conditions

Temperature
60 °C

Procedure

345(c) The 1,1-dimethylethyl (2S)-4-[(5′-{[({2-chloro-5-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)sulfonyl]-4-fluorophenyl}carbonyl)amino]methyl}-2′-fluoro-3-biphenylyl)methyl]-2-methyl-1-piperazinecarboxylate was dissolved in 2 mL of dioxane:MeOH (3:1). Three drops of HCl (concentrated) were added to the resultant solution and heated at 60° C. for 1 h. The solution was applied to the amine column, rinsed with 10 mL of dioxane:MeOH (3:1) to afford 63.0 mg (75.4%) the title compound. LC-MS m/z 837 (M+H)+, 1.29 min (ret time).

Workup

  1. washrinsed with 10 mL of dioxane:MeOH (3:1)

Sources & evidence

ORD record
ord-ac939f8794214526a014555a50346b4e
Source dataset
uspto-grants-2011_11
Patent number
US08067408B2

Reaction notes

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