Trifluoroacetic acid → N-({3'-[(1S,4S)-2,5-Diazabicyclo [2.2.1]hept-2-ylmethyl]-6-fluoro-3-biphenylyl}methyl)-N'-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-1,3-benzenedicarboxamide

HRID 564583Notes

Reaction equation

HRID 564583 reaction equation
[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:61][CH3:62])=[C:10]([CH2:19][NH:20][C:21]([C:23]3[CH:24]=[C:25]([C:29]([NH:31][CH2:32][C:33]4[CH:34]=[CH:35][C:36]([F:60])=[C:37]([C:39]5[CH:44]=[CH:43][CH:42]=[C:41]([CH2:45][N:46]6[CH2:51][C@@H:50]7[CH2:52][C@H:47]6[CH2:48][N:49]7C(OC(C)(C)C)=O)[CH:40]=5)[CH:38]=4)=[O:30])[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].FC(F)(F)C(O)=O>C(Cl)Cl.CCOC(C)=O>[C@H:47]12[CH2:52][C@H:50]([NH:49][CH2:48]1)[CH2:51][N:46]2[CH2:45][C:41]1[CH:40]=[C:39]([C:37]2[C:36]([F:60])=[CH:35][CH:34]=[C:33]([CH2:32][NH:31][C:29]([C:25]3[CH:26]=[CH:27][CH:28]=[C:23]([C:21]([NH:20][CH2:19][C:10]4[C:11]([NH:12][CH:13]5[CH2:14][CH2:15][O:16][CH2:17][CH2:18]5)=[C:6]5[CH:5]=[N:4][N:3]([CH2:1][CH3:2])[C:7]5=[N:8][C:9]=4[CH2:61][CH3:62])=[O:22])[CH:24]=3)=[O:30])[CH:38]=2)[CH:44]=[CH:43][CH:42]=1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acid2×HCID 57813322HCID 57813322, compound

Product 1

HCID 57813497N-({3'-[(1S,4S)-2,5-Diazabicyclo [2.2.1]hept-2-ylmethyl]-6-fluoro-3-biphenylyl}methyl)-N'-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-1,3-benzenedicarboxamide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

1,1-Dimethylethyl (1S,4S)-5-[(5′-{[({3-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]phenyl}-carbonyl)amino]methyl}-2′-fluoro-3-biphenylyl)methyl]-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (0.0488 g, 0.058 mmol) was dissolved in CH2Cl2 (9 mL) and treated with trifluoroacetic acid (1 mL) at 0° C. and then allowed to warm to room temperature. This mixture was stirred for a total of 2 h. The solvents were pumped off, and the material was passed though 2 quaternary ammonium hydroxide cartridges, but 19F NMR still indicated residual TFA. The product was taken up in EtOAc and washed 3× with 0.5 N NaOH, 1× with brine, dried over anhydrous Na2SO4, filtered, and concentrated to give the title compound as a tan solid. LC-MS m/z 746 (M+H)+, 1.30 min (ret time); mp 129-133° C. Analytical HPLC shows 96.8% purity, (ret time 9.820 min).

Workup

  1. washwashed 3× with 0.5 N NaOH, 1× with brine
  2. dry with materialdried over anhydrous Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-da6ad0652585437294f21df97a4451cf
Source dataset
uspto-grants-2011_11
Patent number
US08067408B2

Reaction notes

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