Acetonitrile → 5-(4-(Tetrahydro-2H-pyran-4-yloxy)-1H-pyrazolo[4,3-c]pyridin-3-yl)quinoline

HRID 1046504Notes

Reaction equation

HRID 1046504 reaction equation
I[C:2]1[C:6]2[C:7]([O:11][CH:12]3[CH2:17][CH2:16][O:15][CH2:14][CH2:13]3)=[N:8][CH:9]=[CH:10][C:5]=2[N:4](C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[N:3]=1.[N:37]1[C:46]2[C:41](=[C:42](B(O)O)[CH:43]=[CH:44][CH:45]=2)[CH:40]=[CH:39][CH:38]=1.C(=O)([O-])[O-].[Na+].[Na+].C(#N)C.C([SiH](CC)CC)C.FC(F)(F)C(O)=O>>[O:15]1[CH2:16][CH2:17][CH:12]([O:11][C:7]2[C:6]3[C:2]([C:42]4[CH:43]=[CH:44][CH:45]=[C:46]5[C:41]=4[CH:40]=[CH:39][CH:38]=[N:37]5)=[N:3][NH:4][C:5]=3[CH:10]=[CH:9][N:8]=2)[CH2:13][CH2:14]1

Participants

7

Reactant 6

HCID 6342AcetonitrileHCID 6422Trifluoroacetic acidHCID 10340Sodium CarbonateHCID 12052TriethylsilaneHCID 5153389Quinolin-5-ylboronic acidHCID 66826813HCID 66826813, compound

Product 1

HCID 668291545-(4-(Tetrahydro-2H-pyran-4-yloxy)-1H-pyrazolo[4,3-c]pyridin-3-yl)quinolineYield 43.3%

Conditions

Temperature
0 °C

Procedure

To a microwave tube was added 3-iodo-4-(tetrahydro-2H-pyran-4-yloxy)-1-trityl-1H-pyrazolo[4,3-c]pyridine (120 mg, 0.20 mmol), quinolin-5-ylboronic acid (43 mg, 0.25 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium (14 mg, 0.02 mmol), a 2 M aqueous solution of sodium carbonate (0.20 mL) and acetonitrile (1.5 mL, 0.029 mmol). The tube was then sealed and the reaction was irradiated in a microwave reactor at 140° C. for 30 minutes. The reaction mixture was filtered through Celite® and concentrated. The crude residue was then dissolved in DCM (3 mL) and cooled to 0° C. To the cooled reaction mixture was added triethylsilane (0.13 mL, 0.80 mmol) and trifluoroacetic acid (3.0 mL, 0.039 mmol). The mixture was stirred at room temperature for 30 minutes before concentrated under vacuum. The resulting residue was re-suspended in methanol and filtered to remove insoluble solids. The filtrate was concentrated and purified by reverse-phase HPLC to give the title compound (30 mg, 43%). LC-MS (Method G): m/z=347.1 [M+H]+; 2.98 min. 1H-NMR (400 MHz, DMSO): δ 13.69 (s, 1H), 8.94 (s, 1H), 8.23 (d, J=8.4, 1H), 8.14 (d, J=8.3, 1H), 7.89 (m, 2H), 7.78 (d, J=6.8, 1H), 7.49 (m, 1H), 7.22 (m, 1H), 5.28 (m, 1H), 3.24 (m, 2H), 3.06 (m, 2H), 1.69 (m, 2H), 1.17 (m, 3H).

Workup

  1. customThe tube was then sealed
  2. customthe reaction was irradiated in a microwave reactor at 140° C. for 30 minutes
  3. filtrationThe reaction mixture was filtered through Celite®
  4. concentrationconcentrated
  5. dissolutionThe crude residue was then dissolved in DCM (3 mL)
  6. customTo the cooled reaction mixture
  7. concentrationbefore concentrated under vacuum
  8. filtrationfiltered
  9. customto remove insoluble solids
  10. concentrationThe filtrate was concentrated
  11. custompurified by reverse-phase HPLC

Sources & evidence

ORD record
ord-049e9f44b27c47a0a56848532c6f5311
Source dataset
uspto-grants-2013_10
Patent number
US08569281B2

Reaction notes

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