Ethanol → HCID 178463540, compound

HRID 717859Notes

Reaction equation

HRID 717859 reaction equation
[Cl:1][C:2]1[C:3]2[N:4]([N:18]=[CH:19][CH:20]=2)[C:5]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[CH:12]=2)=[C:6]([CH:8]([NH2:10])[CH3:9])[CH:7]=1.Br[C:22]1[N:30]=[CH:29][N:28]=[C:27]2[C:23]=1[N:24]=[CH:25][N:26]2C1CCCCO1.C(O)C.C(N(CC)C(C)C)(C)C>Cl.O1CCOCC1>[Cl:1][C:2]1[C:3]2[N:4]([N:18]=[CH:19][CH:20]=2)[C:5]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[CH:12]=2)=[C:6]([CH:8]([NH:10][C:22]2[N:30]=[CH:29][N:28]=[C:27]3[C:23]=2[N:24]=[CH:25][NH:26]3)[CH3:9])[CH:7]=1

Participants

7

Reactant 4

HCID 702EthanolHCID 81531DiisopropylethylamineHCID 583686166-Bromo-9-(tetrahydro-2H-pyran-2-YL)-9H-purineHCID 58515974HCID 58515974, compound

Product 1

HCID 178463540HCID 178463540, compoundYield 47%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

1-[4-Chloro-7-(3-fluorophenyl)pyrazolo[1,5-a]pyridin-6-yl]ethanamine (12 mg, 0.043 mmol) and 6-bromo-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (0.018 g, 0.064 mmol) were stirred in ethanol (0.5 mL, 9 mmol) with N,N-diisopropylethylamine (37 μL, 0.21 mmol). The mixture was heated to 100° C. for 20 hours, the reaction was mostly complete. This was allowed to cool to room temperature and concentrated in vacuo to give a semi-solid residue. The residue was taken up in 4 M HCl in dioxane and stirred at room temperature for 1 hour. This was complete by LCMS and was concentrated to give a semi-solid residue. The product was purified by preparative HPLC on a C-18 column eluting acetonitrile: water gradient buffered with ammonia to pH 10 to give N-{1-[4-chloro-7-(3-fluorophenyl)pyrazolo[1,5-a]pyridin-6-yl]ethyl}-9H-purin-6-amine (8 mg, 47%) as a white amorphous solid. LCMS calculated for C20H16ClFN7 (M+H)+: m/z=408.1. found: 408.0. 1H NMR (400 MHz, DMSO-d6/TFA): δ 8.52 (m, 1H), 8.42 (m, 1H), 7.98 (m, 1H), 7.69 (m, 1H), 7.63-7.51 (m, 2H), 7.45-7.31 (m, 2H), 6.77 (m, 1H), 5.1 (m, 1H), 1.55 (d, 3H).

Workup

  1. temperatureto cool to room temperature
  2. concentrationconcentrated in vacuo
  3. customto give a semi-solid residue
  4. concentrationThis was complete by LCMS and was concentrated
  5. customto give a semi-solid residue
  6. customThe product was purified by preparative HPLC on a C-18 column
  7. washeluting acetonitrile

Sources & evidence

ORD record
ord-73cc1892dff5457da52a091a82ddad6c
Source dataset
uspto-grants-2015_11
Patent number
US09193721B2

Reaction notes

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