Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → Methyl 3-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]-5-methylbenzoate

HRID 564501

Reaction equation

HRID 564501 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([C:11]([O:13][CH3:14])=[O:12])[CH:10]=1)[C:5]([OH:7])=O.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[NH2:40][CH2:41][C:42]1[C:47]([CH2:48][CH3:49])=[N:46][C:45]2[N:50]([CH2:53][CH3:54])[N:51]=[CH:52][C:44]=2[C:43]=1[NH:55][CH:56]1[CH2:61][CH2:60][O:59][CH2:58][CH2:57]1>ClCCl>[CH2:53]([N:50]1[C:45]2=[N:46][C:47]([CH2:48][CH3:49])=[C:42]([CH2:41][NH:40][C:5]([C:4]3[CH:8]=[C:9]([CH:10]=[C:2]([CH3:1])[CH:3]=3)[C:11]([O:13][CH3:14])=[O:12])=[O:7])[C:43]([NH:55][CH:56]3[CH2:57][CH2:58][O:59][CH2:60][CH2:61]3)=[C:44]2[CH:52]=[N:51]1)[CH3:54]

Participants

5

Reactant 3

HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 72108363-(Methoxycarbonyl)-5-methylbenzoic acidHCID 670055525-(aminomethyl)-1,6-diethyl-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-amine hydrochloride

Product 1

HCID 57813541Methyl 3-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]-5-methylbenzoate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3-Methyl-5-[(methyloxy)carbonyl]benzoic acid (2.91 g, 15.00 mmol) was partially dissolved in dichloromethane (DCM) (500 mL) with stirring under argon at room temperature. HBTU (5.69 g, 15.00 mmol) was added followed by 5-(aminomethyl)-1,6-diethyl-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-amine hydrochloride (5.10 g, 15 mmol), and then TEA (4.18 mL, 30.0 mmol). The mixture was stirred under argon overnight. The solvent was concentrated and the residue partitioned between EtOAc (300 mL) and water (100 mL). The organic phase was washed with water (3×100 mL), brine, dried over anhydrous sodium sulfate, filtered and concentrated to give the crude product. This was purified by CombiFlash on a 120 g silica column eluted with 35-100% EtOAc in hexane. The purified product was taken up in 300 mL of EtOAc, and washed with 50 mL of 1N NaOH, and then with water (3×100 mL), and 50 mL of brine, dried over anhydrous sodium sulfate, filtered and concentrated to give the title compound as a white solid. LC-MS m/z 480.0 (M+H)+, 0.81 min (ret time); mp 89-93° C.; analytical HPLC shows 95.4% purity, (ret time 12.251 min).

Workup

  1. stirringThe mixture was stirred under argon overnight
  2. concentrationThe solvent was concentrated
  3. customthe residue partitioned between EtOAc (300 mL) and water (100 mL)
  4. washThe organic phase was washed with water (3×100 mL), brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give the crude product
  9. customThis was purified by CombiFlash on a 120 g silica column
  10. washeluted with 35-100% EtOAc in hexane
  11. washwashed with 50 mL of 1N NaOH
  12. dry with materialwith water (3×100 mL), and 50 mL of brine, dried over anhydrous sodium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-19ab3e8468e245a6a7b9cc460056a92a
Source dataset
uspto-grants-2011_11
Patent number
US08067408B2

Linked notes

Loading…