Trifluoroacetic acid → HCID 57813525, compound

HRID 564654Notes

Reaction equation

HRID 564654 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:41]=[CH:40][N:39]=[C:38]([C:42]2[CH:43]=[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:45]=[CH:46][CH:47]=2)[CH:37]=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>ClCCl.CO.CS(C)=O>[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:41]=[CH:40][N:39]=[C:38]([C:42]5[CH:47]=[CH:46][CH:45]=[C:44]([CH2:48][CH:49]6[CH2:50][CH2:51][NH:52][CH2:53][CH2:54]6)[CH:43]=5)[CH:37]=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

7

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 57813321HCID 57813321, compound

Product 1

HCID 57813525HCID 57813525, compoundYield 36.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 22036561Dimethyl sulfoxide methanolSolvent

Procedure

To 3-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]benzoic acid (30 mg, 0.066 mmol) was added 1,1-dimethylethyl 4-({3-[4-(aminomethyl)-2-pyridinyl]phenyl}methyl)-1-piperidinecarboxylate (25.3 mg, 0.066 mmol) followed by HBTU (30.2 mg, 0.080 mmol) and TEA (13.45 mg, 0.133 mmol) in dichloromethane (DCM) (664 μl) to give a reaction mixture that was stirred at room temperature overnight. Then the reaction was quenched with H2O (1 drop) and the solvent was removed by Glas-Col. The crude product was redissolved in MeOH/DMSO and purified using a Gilson HPLC (acidic conditions) and concentrated by GeneVav EZ-2 evaporator. To this product was added TFA (93 μl, 1.329 mmol) in dichloromethane (0.2 mL) which was then stirred at room temperature overnight. The reaction mixture was dissolved in MeOH/DMSO and purified using a Gilson HPLC (acidic conditions), concentrated by GeneVav EZ-2 evaporator and basified with an amine cartridge to afford 17.1 mg (32%) of the title compound. LC-MS m/z 715 (M+H)+; 1H NMR (400 MHz, DMSO-d6) δ 1.23-1.42 (m, 6 H) 1.68-1.76 (m, 3 H) 1.79-2.02 (m, 3 H) 2.08 (s, 2 H) 2.63 (d, J=6.78 Hz, 2 H) 2.76-2.84 (m, 2 H) 3.07-3.15 (m, 2 H) 3.20-3.28 (m, 2 H) 3.32-3.39 (m, 1 H) 3.58-3.66 (m, 2 H) 3.90 (dd, J=8.03, 3.51 Hz, 2 H) 4.29-4.37 (m, 1 H) 4.47 (q, J=7.19 Hz, 2 H) 4.60 (t, J=6.40 Hz, 4 H) 7.28 (d, J=7.78 Hz, 1 H) 7.34 (d, J=3.76 Hz, 1 H) 7.39-7.46 (m, 1 H) 7.65 (t, J=7.78 Hz, 1 H) 7.85 (d, J=8.03 Hz, 1 H) 7.92 (d, J=14.56 Hz, 2 H) 8.05 (d, J=8.03 Hz, 1 H) 8.12 (d, J=7.78 Hz, 1 H) 8.26 (br. s., 1 H) 8.40 (s, 2 H) 8.61 (d, J=4.52 Hz, 1 H) 8.86 (br. s., 1 H) 9.32-9.39 (m, 2 H).

Workup

  1. customto give a reaction mixture that
  2. customThen the reaction was quenched with H2O (1 drop)
  3. customthe solvent was removed by Glas-Col
  4. dissolutionThe crude product was redissolved in MeOH/DMSO
  5. custompurified
  6. concentrationconcentrated by GeneVav EZ-2 evaporator
  7. stirringwas then stirred at room temperature overnight
  8. custompurified
  9. concentrationconcentrated by GeneVav EZ-2 evaporator

Sources & evidence

ORD record
ord-08679c080b54408f82e9f14e5be98b4a
Source dataset
uspto-grants-2011_11
Patent number
US08067408B2

Reaction notes

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