Trifluoroacetic acid → HCID 57813477, compound

HRID 564653Notes

Reaction equation

HRID 564653 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][N:49]3[CH2:54][CH2:53][N:52](C(OC(C)(C)C)=O)[C@@H:51]([CH3:62])[CH2:50]3)[CH:45]=[CH:46][CH:47]=2)[CH:37]=1.CN(C(ON1N=N[C:73]2[CH:74]=C[CH:76]=[CH:77][C:72]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:87]([OH:93])([C:89](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:73]3[CH:72]=[CH:77][CH:76]=[C:89]([C:87]([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][N:49]6[CH2:54][CH2:53][NH:52][C@@H:51]([CH3:62])[CH2:50]6)[CH:43]=5)[CH:37]=4)=[O:93])[CH:74]=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 57813432HCID 57813432, compound

Product 1

HCID 57813477HCID 57813477, compoundYield 34.5%

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 (2S)-4-({3-[4-(aminomethyl)-2-pyridinyl]phenyl}methyl)-2-methyl-1-piperazinecarboxylate (26.3 mg, 0.066 mmol) followed by HBTU (30.2 mg, 0.080 mmol) and TEA (18.52 μl, 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 by 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), concentrated by GeneVav EZ-2 evaporator. To this product was added TFA (102 μl, 1.329 mmol) in dichloromethane (0.2 mL) 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 16.6 mg (33%) of the title compound. LC-MS m/z 730 (M+H)+.

Workup

  1. customto give a reaction mixture that
  2. customThen the reaction was quenched by 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. stirringthen stirred at room temperature overnight
  8. custompurified
  9. concentrationconcentrated by GeneVav EZ-2 evaporator

Sources & evidence

ORD record
ord-7a8314754f634845a7282bf3a132f8fd
Source dataset
uspto-grants-2011_11
Patent number
US08067408B2

Reaction notes

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