Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → N-{[1,6-Diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N'-({3'-[(1-methyl-4-piperidinyl)methyl]-3-biphenylyl}methyl)-1,3-benzenedicarboxamide

HRID 564642Notes

Reaction equation

HRID 564642 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([CH2:8][C:9]2[CH:10]=[C:11]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([CH2:21][NH2:22])[CH:16]=3)[CH:12]=[CH:13][CH:14]=2)[CH2:4][CH2:3]1.[CH2:23]([N:25]1[C:29]2=[N:30][C:31]([CH2:54][CH3:55])=[C:32]([CH2:41][NH:42][C:43]([C:45]3[CH:46]=[C:47]([CH:51]=[CH:52][CH:53]=3)[C:48](O)=[O:49])=[O:44])[C:33]([NH:34][CH:35]3[CH2:40][CH2:39][O:38][CH2:37][CH2:36]3)=[C:28]2[CH:27]=[N:26]1)[CH3:24].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[CH2:23]([N:25]1[C:29]2=[N:30][C:31]([CH2:54][CH3:55])=[C:32]([CH2:41][NH:42][C:43]([C:45]3[CH:53]=[CH:52][CH:51]=[C:47]([C:48]([NH:22][CH2:21][C:17]4[CH:16]=[C:15]([C:11]5[CH:12]=[CH:13][CH:14]=[C:9]([CH2:8][CH:5]6[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]6)[CH:10]=5)[CH:20]=[CH:19][CH:18]=4)=[O:49])[CH:46]=3)=[O:44])[C:33]([NH:34][CH:35]3[CH2:40][CH2:39][O:38][CH2:37][CH2:36]3)=[C:28]2[CH:27]=[N:26]1)[CH3:24]

Participants

5

Reactant 3

HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57813254({3'-[(1-Methyl-4-piperidinyl)methyl]-3-biphenylyl}methyl)amineHCID 578132773-[({[1,6-Diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]benzoic Acid

Product 1

HCID 57813386N-{[1,6-Diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N'-({3'-[(1-methyl-4-piperidinyl)methyl]-3-biphenylyl}methyl)-1,3-benzenedicarboxamideYield 59.34%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of ({3′-[(1-methyl-4-piperidinyl)methyl]-3-biphenylyl}methyl)amine (0.0294 g, 0.10 mmol) in DCM (1 mL) was added 3-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]benzoic acid (0.0452 g, 0.10 mmol), HBTU (0.0417 g, 0.11 mmol), and TEA (0.0303 mL, 0.20 mmol) and was stirred at room temperature for 17 h. The reaction was quenched with H2O (1 drop), concentrated by Glas-Col evaporator and re-dissolved in MeOH/DMSO (0.5/0.1 mL). The resultant mixture was purified using a Gilson HPLC (with 0.1% TFA), concentrated by GeneVac EZ-2 evaporator and basified with an amine cartridge to afford the title compound 0.0432 g (59.34%). LC-MS m/z 728 (M+H)+; 1H NMR (400 MHz, CD3OD) δ ppm 1.37-1.44 (m, 3 H) 1.46-1.54 (m, J=7.28, 7.28 Hz, 5 H) 1.81-1.98 (m, 5 H) 2.05-2.13 (m, J=12.55 Hz, 2 H) 2.68 (d, J=6.53 Hz, 2 H) 2.78-2.86 (m, 3 H) 2.88-2.97 (m, 2 H) 3.15 (q, J=7.61 Hz, 2 H) 3.43-3.51 (m, J=12.30 Hz, 2 H) 3.67 (t, J=11.54 Hz, 2 H) 4.03 (d, J=11.80 Hz, 2 H) 4.30-4.41 (m, 1 H) 4.47 (q, J=7.19 Hz, 2 H) 4.65 (s, 2 H) 4.71 (s, 2 H) 7.17 (d, J=7.53 Hz, 1 H) 7.33-7.53 (m, 6 H) 7.59-7.66 (m, 2 H) 8.05 (dd, J=7.91, 1.63 Hz, 2 H) 8.29 (s, 1 H) 8.39 (s, 1 H).

Workup

  1. customThe reaction was quenched with H2O (1 drop)
  2. concentrationconcentrated by Glas-Col evaporator
  3. dissolutionre-dissolved in MeOH/DMSO (0.5/0.1 mL)
  4. customThe resultant mixture was purified
  5. concentrationconcentrated by GeneVac EZ-2 evaporator

Sources & evidence

ORD record
ord-62960e60c7544ac48c1adcd146efe63f
Source dataset
uspto-grants-2011_11
Patent number
US08067408B2

Reaction notes

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