Triethylamine → 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}amino)sulfonyl]benzamide

HRID 564645Notes

Reaction equation

HRID 564645 reaction equation
[NH2:1][CH2:2][C:3]1[C:8]([CH2:9][CH3:10])=[N:7][C:6]2[N:11]([CH2:14][CH3:15])[N:12]=[CH:13][C:5]=2[C:4]=1[NH:16][CH:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1.CC(OC([N:30]1[CH2:35][CH2:34][N:33]([CH2:36][C:37]2[CH:38]=[C:39]([C:43]3[C:48]([F:49])=[CH:47][CH:46]=[C:45]([CH2:50][NH:51][S:52]([C:55]4[CH:56]=[C:57]([CH:61]=[CH:62][CH:63]=4)[C:58](O)=[O:59])(=[O:54])=[O:53])[CH:44]=3)[CH:40]=[CH:41][CH:42]=2)[CH2:32][CH2:31]1)=O)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(CC)CC>C(Cl)Cl>[CH2:14]([N:11]1[C:6]2=[N:7][C:8]([CH2:9][CH3:10])=[C:3]([CH2:2][NH:1][C:58](=[O:59])[C:57]3[CH:61]=[CH:62][CH:63]=[C:55]([S:52]([NH:51][CH2:50][C:45]4[CH:44]=[C:43]([C:39]5[CH:40]=[CH:41][CH:42]=[C:37]([CH2:36][N:33]6[CH2:34][CH2:35][NH:30][CH2:31][CH2:32]6)[CH:38]=5)[C:48]([F:49])=[CH:47][CH:46]=4)(=[O:54])=[O:53])[CH:56]=3)[C:4]([NH:16][CH:17]3[CH2:18][CH2:19][O:20][CH2:21][CH2:22]3)=[C:5]2[CH:13]=[N:12]1)[CH3:15]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 578134033-{[({3'-[(4-{[(1,1-Dimethyl ethyl)oxy]carbonyl}-1-piperazinyl)methyl]-6-fluoro-3-biphenylyl}methyl)amino]sulfonyl}benzoic acidHCID 596832145-(Aminomethyl)-1,6-diethyl-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-amine

Product 1

HCID 57813526N-{[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}amino)sulfonyl]benzamideYield 33%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-(aminomethyl)-1,6-diethyl-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridine-4-amine (0.0195 g, 0.0641 mmol) in DCM (0.64 mL) was added 3-{[({3′-[(4-{[(1,1-dimethyl ethyl)oxy]carbonyl}-1-piperazinyl)methyl]-6-fluoro-3-biphenylyl}methyl)amino]sulfonyl}benzoic acid (0.0374 g, 0.0641 mmol), HBTU (0.0365 g, 0.0962 mmol), Et3N (0.018 mL, 0.128 mmol). The result mixture was stirred at room temperature for 21 h before it was concentrated and purified using a Gilson HPLC (w/TFA). The HPLC fraction was concentrated on a GeneVac EZ-2 evaporator at 45° C. (de-Boc completed during evaporation), basified with an amine cartridge to afford 0.0161 g (33%) of the title compound. LC-MS m/z 769 (M+H)+; 1H-NMR (400 MHz, MeOD) δ ppm 1.41 (t, J=7.30 Hz, 3 H) 1.49 (t, J=7.05 Hz, 3 H) 1.86 (q, J=9.90 Hz, 2 H) 2.09 (d, J=12.34 Hz, 2 H) 3.17 (q, J=7.39 Hz, 2 H) 3.46-3.59 (m, J=12.59 Hz, 8 H) 3.67 (t, J=11.33 Hz, 2 H) 4.04 (d, J=11.83 Hz, 2 H) 4.16 (s, 2 H) 4.30-4.39 (m, 1 H) 4.41 (s, 2 H) 4.48 (q, J=6.88 Hz, 2 H) 4.70 (s, 2 H) 7.04 (t, J=9.44 Hz, 1 H) 7.18-7.27 (m, 1 H) 7.34 (d, J=7.05 Hz, 1 H) 7.50-7.58 (m, 3 H) 7.60-7.68 (m, 2 H) 7.98 (d, J=7.55 Hz, 1 H) 8.08 (d, J=7.81 Hz, 1 H) 8.30 (d, J=13.60 Hz, 2 H).

Workup

  1. concentrationwas concentrated
  2. custompurified
  3. concentrationThe HPLC fraction was concentrated on a GeneVac EZ-2 evaporator at 45° C.
  4. custom(de-Boc completed during evaporation)

Sources & evidence

ORD record
ord-c49acab91b134f0786b965a12e051caf
Source dataset
uspto-grants-2011_11
Patent number
US08067408B2

Reaction notes

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