1,2-Dichloroethane → 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

HRID 564647Notes

Reaction equation

HRID 564647 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([F:11])[C:8]([S:12]([NH:15][CH2:16][C:17]2[C:18]([NH:30][CH:31]3[CH2:36][CH2:35][O:34][CH2:33][CH2:32]3)=[C:19]3[CH:27]=[N:26][N:25]([CH2:28][CH3:29])[C:20]3=[N:21][C:22]=2[CH2:23][CH3:24])(=[O:14])=[O:13])=[CH:7][C:3]=1[C:4](O)=[O:5].[NH2:37][CH2:38][C:39]1[CH:40]=[CH:41][C:42]([F:66])=[C:43]([C:45]2[CH:50]=[CH:49][CH:48]=[C:47]([CH2:51][N:52]3[CH2:57][CH2:56][N:55]([C:58]([O:60][C:61]([CH3:64])([CH3:63])[CH3:62])=[O:59])[C@@H:54]([CH3:65])[CH2:53]3)[CH:46]=2)[CH:44]=1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>C(Cl)Cl>[Cl:1][C:2]1[CH:10]=[C:9]([F:11])[C:8]([S:12]([NH:15][CH2:16][C:17]2[C:18]([NH:30][CH:31]3[CH2:32][CH2:33][O:34][CH2:35][CH2:36]3)=[C:19]3[CH:27]=[N:26][N:25]([CH2:28][CH3:29])[C:20]3=[N:21][C:22]=2[CH2:23][CH3:24])(=[O:13])=[O:14])=[CH:7][C:3]=1[C:4]([NH:37][CH2:38][C:39]1[CH:40]=[CH:41][C:42]([F:66])=[C:43]([C:45]2[CH:50]=[CH:49][CH:48]=[C:47]([CH2:51][N:52]3[CH2:57][CH2:56][N:55]([C:58]([O:60][C:61]([CH3:62])([CH3:64])[CH3:63])=[O:59])[C@@H:54]([CH3:65])[CH2:53]3)[CH:46]=2)[CH:44]=1)=[O:5]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 251325161,1-dimethylethyl (2S)-4-{[5'-(aminomethyl)-2'-fluoro-3-biphenylyl]methyl}-2-methyl-1-piperazinecarboxylateHCID 578132602-chloro-5-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)sulfonyl]-4-fluorobenzoic acid

Product 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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

345(b) The 2-chloro-5-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)sulfonyl]-4-fluorobenzoic acid, was dissolved in 3 mL of DCM with 1,1-dimethylethyl (2S)-4-{[5′-(aminomethyl)-2′-fluoro-3-biphenylyl]methyl}-2-methyl-1-piperazinecarboxylate (41.3 mg, 0.1 mmol), and then added in HOBt (1.0 eq, 14.0 mg), and EDC (1.0 eq, 19.0 mg). The resultant solution was stirred overnight. The solution was then purified using a Gilson to give 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.

Workup

  1. customThe solution was then purified

Sources & evidence

ORD record
ord-f09bc4039ca94aa99d81e81ba9be0523
Source dataset
uspto-grants-2011_11
Patent number
US08067408B2

Reaction notes

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