Trifluoroacetic acid → HCID 44193618, compound

HRID 662128Notes

Reaction equation

HRID 662128 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]([C:23]3[N:28]=C(C(O)=O)[CH:26]=[CH:25][CH:24]=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].[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=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:87]([OH:93])([C:89](F)(F)F)=O>ClCCl>[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:23]3[CH:24]=[CH:25][CH:26]=[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])[N:28]=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 57813432HCID 57813432, compoundHCID 578193746-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]-2-pyridinecarboxylic acid

Product 1

HCID 44193618HCID 44193618, compoundYield 39.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To 6-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]-2-pyridinecarboxylic 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 (18.48 μl, 0.133 mmol) in dichloromethane (DCM) (663 μL) to give a reaction mixture which was stirred at room temperature overnight. Then the reaction was quenched with H2O (1 drop) and the solvent was removed using a Glas-Col. The crude product was redissolved in MeOH/DMSO (1/1) and purified by Gilson HPLC (acidic condition). Product fractions were evaporated by GeneVac EZ-2 evaporator. To this material was added TFA (0.102 mL, 1.33 mmol) in dichloromethane (0.2 mL) and it was placed in the Glas-Col evaporator overnight. It was redissolved in MeOH/DMSO and purified using a Gilson HPLC (acidic condition). Product fractions were evaporated by GeneVac EZ-2 evaporator, basified by cartridge to afford 19.1 mg (37%) of the title compound. LC-MS m/z 731 (M+H)+.

Workup

  1. customto give a reaction mixture which
  2. customThen the reaction was quenched with H2O (1 drop)
  3. customthe solvent was removed
  4. dissolutionThe crude product was redissolved in MeOH/DMSO (1/1)
  5. custompurified by Gilson HPLC (acidic condition)
  6. customProduct fractions were evaporated by GeneVac EZ-2 evaporator
  7. customwas placed in the Glas-Col evaporator overnight
  8. dissolutionIt was redissolved in MeOH/DMSO
  9. custompurified
  10. customProduct fractions were evaporated by GeneVac EZ-2 evaporator

Sources & evidence

ORD record
ord-6962e3a1ff0f40ec872fc874a066f1f0
Source dataset
uspto-grants-2011_12
Patent number
US08084449B2

Reaction notes

Loading…