Trifluoroacetic acid → N-{[1,6-Diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-3-{[{[6-fluoro-3'-(1-piperazinylmethyl)-3-biphenylyl]methyl}(methyl)amino]methyl}benzamide

HRID 564596Notes

Reaction equation

HRID 564596 reaction equation
[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:60][CH3:61])=[C:10]([CH2:19][NH:20][C:21]([C:23]3[CH:24]=[C:25]([CH2:29][N:30]([CH2:32][C:33]4[CH:34]=[CH:35][C:36]([F:59])=[C:37]([C:39]5[CH:44]=[CH:43][CH:42]=[C:41]([CH2:45][N:46]6[CH2:51][CH2:50][N:49](C(OC(C)(C)C)=O)[CH2:48][CH2:47]6)[CH:40]=5)[CH:38]=4)[CH3:31])[CH:26]=[CH:27][CH:28]=3)=[O:22])[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].C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:60][CH3:61])=[C:10]([CH2:19][NH:20][C:21](=[O:22])[C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([CH2:29][N:30]([CH2:32][C:33]4[CH:38]=[C:37]([C:39]5[CH:44]=[CH:43][CH:42]=[C:41]([CH2:45][N:46]6[CH2:51][CH2:50][NH:49][CH2:48][CH2:47]6)[CH:40]=5)[C:36]([F:59])=[CH:35][CH:34]=4)[CH3:31])[CH:24]=3)[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]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 578134271,1-Dimethylethyl 4-[(5'-{[({3-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino) carbonyl]phenyl}methyl)(methyl)amino]methyl}-2'-fluoro-3-biphenylyl)methyl]-1-piperazinecarboxylate

Product 1

HCID 44180875N-{[1,6-Diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-3-{[{[6-fluoro-3'-(1-piperazinylmethyl)-3-biphenylyl]methyl}(methyl)amino]methyl}benzamideYield 20%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1,1-dimethylethyl 4-[(5′-{[({3-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]-phenyl}methyl)(methyl)amino]-methyl}-2′-fluoro-3-biphenylyl)methyl]-1-piperazinecarboxylate (0.386 g, 0.463 mmol) in DCM (3.6 mL) was added TFA (1.8 mL) and this mixture was stirred at room temperature for 100 min before being quenched with NaHCO3 (sat. aq.). This mixture was extracted with DCM, concentrated, purified using a Gilson HPLC (with TFA). Product was basified with an amine cartridge to afford 0.068 g (20%) of the title compound. LC-MS m/z 733 (M+H)+; 1H-NMR (400 MHz, CD3OD) δ ppm 1.40 (t, J=7.65 Hz, 3 H) 1.49 (t, J=7.15 Hz, 3 H) 1.79-1.92 (m, 2 H) 2.05-2.14 (m, 2 H) 2.74 (s, 3 H) 3.18 (q, J=7.61 Hz, 2 H) 3.43-3.58 (m, 8 H) 3.63-3.72 (m, 2 H) 3.99-4.07 (m, 2 H) 4.30-4.62 (m, 9 H) 4.72 (s, 2 H) 7.34 (dd, J=10.42, 8.66 Hz, 1 H) 7.54-7.65 (m, 4 H) 7.67-7.78 (m, 4 H) 8.02 (d, J=8.03 Hz, 1 H) 8.12 (s, 1 H) 8.29 (s, 1 H).

Workup

  1. custombefore being quenched with NaHCO3 (sat. aq.)
  2. extractionThis mixture was extracted with DCM
  3. concentrationconcentrated
  4. custompurified

Sources & evidence

ORD record
ord-0e89a178332e42c9a4b6b1137f42cc08
Source dataset
uspto-grants-2011_11
Patent number
US08067408B2

Reaction notes

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