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

HRID 564544Notes

Reaction equation

HRID 564544 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[CH:24]=[C:25]([CH:29]=[CH:30][CH:31]=3)[C:26](O)=[O:27])=[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].Cl.[Br:35][C:36]1[C:37]([CH3:44])=[C:38]([CH2:42][NH2:43])[CH:39]=[CH:40][CH:41]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[Br:35][C:36]1[C:37]([CH3:44])=[C:38]([CH2:42][NH:43][C:26]([C:25]2[CH:29]=[CH:30][CH:31]=[C:23]([C:21]([NH:20][CH2:19][C:10]3[C:11]([NH:12][CH:13]4[CH2:18][CH2:17][O:16][CH2:15][CH2:14]4)=[C:6]4[CH:5]=[N:4][N:3]([CH2:1][CH3:2])[C:7]4=[N:8][C:9]=3[CH2:32][CH3:33])=[O:22])[CH:24]=2)=[O:27])[CH:39]=[CH:40][CH:41]=1

Participants

5

Reactant 3

HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)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 670065313-Bromo-2-methyl-benzylamine hydrochloride

Product 1

HCID 57813355N-[(3-Bromo-2-methylphenyl)methyl]-N'-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-1,3-benzenedicarboxamideYield 110.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3-[({[1,6-Diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]benzoic acid (918 mg, 0.002 mol) and [(3-bromo-2-methylphenyl)methyl]amine hydrochloride (521 mg, 0.0022 mol) in DCM (25 mL) was treated with HATU (912 mg, 0.0024 mol) followed by TEA (0.404 g, 0.56 mL, 0.004 mol). The reaction was stirred overnight at room temperature. LC-MS showed that the reaction was complete. The reaction was quenched with sat. aq. NaHCO3. The aqueous phase was re-extracted with DCM (2×). Combined organic extracts were washed with H2O, then sat. aq. NaCl and dried (Na2SO4), then concentrated to give a residue (1.4 g). This was purified on the ‘CombiFlash’ using 40 g silica gel column [DCM-MeOH, 0-10%]. This afforded the title compound as a glassy, pale yellow foam [1.35 g (Quant.)]. LC-MS m/z 634.7 (M+H)+.

Workup

  1. customThe reaction was quenched with sat. aq. NaHCO3
  2. extractionThe aqueous phase was re-extracted with DCM (2×)
  3. washCombined organic extracts were washed with H2O
  4. dry with materialsat. aq. NaCl and dried (Na2SO4)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-7f2b8fb2505549e0a349c50b7137673f
Source dataset
uspto-grants-2011_11
Patent number
US08067408B2

Reaction notes

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