Trifluoroacetic acid → n-{[1,6-Diethyl-4-(tetrahydro-2h-pyran-4-ylamino)-1h-pyrazolo[3,4-b]pyridin-5-yl]methyl}-n'-{[3'-(4-piperidinylmethyl)-3-biphenylyl]methyl}-1,3-benzenedicarboxamide

HRID 564641Notes

Reaction equation

HRID 564641 reaction equation
[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:32][CH3:33])=[C:10]([CH2:19][NH:20][C:21](C3C=C(C=CC=3)C(O)=O)=[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].[NH2:34][CH2:35][C:36]1[CH:37]=[C:38]([C:42]2[CH:47]=[CH:46][CH:45]=[C:44]([CH2:48][CH:49]3[CH2:54][CH2:53][N:52](C(OC(C)(C)C)=O)[CH2:51][CH2:50]3)[CH:43]=2)[CH:39]=[CH:40][CH:41]=1.CN(C(ON1N=N[C:72]2[CH:73]=C[CH:75]=[CH:76][C:71]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:86]([OH:92])([C:88](F)(F)F)=O>C(Cl)Cl>[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:32][CH3:33])=[C:10]([CH2:19][NH:20][C:21]([C:72]3[CH:71]=[CH:76][CH:75]=[C:88]([C:86]([NH:34][CH2:35][C:36]4[CH:37]=[C:38]([C:42]5[CH:47]=[CH:46][CH:45]=[C:44]([CH2:48][CH:49]6[CH2:54][CH2:53][NH:52][CH2:51][CH2:50]6)[CH:43]=5)[CH:39]=[CH:40][CH:41]=4)=[O:92])[CH:73]=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]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 578132773-[({[1,6-Diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]benzoic AcidHCID 57813360tert-Butyl 4-{[3'-(aminomethyl)biphenyl-3-yl]methyl}piperidine-1-carboxylate

Product 1

HCID 57813442n-{[1,6-Diethyl-4-(tetrahydro-2h-pyran-4-ylamino)-1h-pyrazolo[3,4-b]pyridin-5-yl]methyl}-n'-{[3'-(4-piperidinylmethyl)-3-biphenylyl]methyl}-1,3-benzenedicarboxamideYield 52%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 3-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]benzoic acid (0.03 g, 0.066 mmol) in DCM (0.66 mL) was added 1,1-dimethylethyl 4-{[3′-(aminomethyl)-3-biphenylyl]methyl}-1-piperidinecarboxylate (0.025 g, 0.066 mmol), HBTU (0.028 g, 0.073 mmol), and TEA (0.014 mL, 0.100 mmol). This mixture was stirred at room temperature for 18 h. The reaction mixture was concentrated (Glas-Col), purified using a Gilson HPLC (with 0.1% TFA) and concentrated with GeneVav EZ-2 evaporator. To the resultant mixture was added DCM (0.1 mL) and TFA (0.033 mL, 0.428 mmol). The resultant mixture was left at room temperature for 30 min before being concentrated on Glas-Col evaporator, purified using a Gilson HPLC (with 0.1% TFA), concentrated with GeneVav EZ-2 and basified with an amine cartridge to afford 0.0245 g (51.7%) of the title compound. LC-MS m/z 714 (M+H)+; 1H NMR (400 MHz, CD3OD) δ ppm 1.35-1.45 (m, J=7.40, 7.40 Hz, 4 H) 1.44-1.53 (m, J=7.15, 7.15 Hz, 4 H) 1.80-1.96 (m, J=13.80 Hz, 5 H) 2.08 (d, J=12.30 Hz, 2 H) 2.66 (d, J=6.53 Hz, 2 H) 2.92 (t, J=12.55 Hz, 2 H) 3.15 (q, J=7.45 Hz, 2 H) 3.35 (d, J=14.31 Hz, 2 H) 3.65 (t, J=11.29 Hz, 2 H) 4.02 (d, J=11.04 Hz, 2 H) 4.27-4.39 (m, 1 H) 4.47 (q, J=7.19 Hz, 2 H) 4.64 (s, 2 H) 4.70 (s, 2 H) 7.16 (d, J=7.28 Hz, 1 H) 7.30-7.54 (m, 6 H) 7.55-7.65 (m, 2 H) 8.05 (d, J=7.78 Hz, 2 H) 8.27 (s, 1 H) 8.40 (s, 1 H).

Workup

  1. concentrationThe reaction mixture was concentrated (Glas-Col)
  2. custompurified
  3. concentrationconcentrated with GeneVav EZ-2 evaporator
  4. concentrationbefore being concentrated on Glas-Col evaporator
  5. custompurified
  6. concentrationconcentrated with GeneVav EZ-2

Sources & evidence

ORD record
ord-7883519606a64f099298817f611b3e1b
Source dataset
uspto-grants-2011_11
Patent number
US08067408B2

Reaction notes

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