Hydrochloric Acid → 5-(2,6-difluorophenyl)-3-(6-(3-pyridinyloxy)-2-pyrazinyl)-1H-indazole

HRID 1529385Notes

Reaction equation

HRID 1529385 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14](C1CCCCO1)[N:13]=[C:12]2[C:24]1[CH:29]=[N:28][CH:27]=[C:26]([O:30][C:31]2[CH:32]=[N:33][CH:34]=[CH:35][CH:36]=2)[N:25]=1.Cl>CO>[F:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[C:3]=1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[C:12]2[C:24]1[CH:29]=[N:28][CH:27]=[C:26]([O:30][C:31]2[CH:32]=[N:33][CH:34]=[CH:35][CH:36]=2)[N:25]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 679596745-(2,6-difluorophenyl)-3-(6-(pyridin-3-yloxy)pyrazin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

Product 1

HCID 679600215-(2,6-difluorophenyl)-3-(6-(3-pyridinyloxy)-2-pyrazinyl)-1H-indazoleYield 93.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 5-(2,6-difluorophenyl)-3-(6-(pyridin-3-yloxy)pyrazin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (74 mg, 0.15 mmol) and HCl (5-6 M in IPA, 3.0 mL, 15.2 mmol) in 4 mL of MeOH was heated at 80° C. for 90 min. The reaction was cooled to RT and concentrated. The residue was diluted with CH2Cl2 and saturated NaHCO3 (aq.) was added slowly. The mixture was extracted with CH2Cl2 (3×). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated to give the title compound (55 mg, 0.14 mmol, 90% yield) as a yellow solid. MS (ESI, pos. ion) m/z: 402.0 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 13.77 (s, 1H), 9.15 (s, 1H), 8.60 (s, 1H), 8.56 (d, J=2.15 Hz, 1H), 7.99 (d, J=4.30 Hz, 1H), 7.82 (dd, J=8.22, 1.37 Hz, 1H), 7.69 (d, J=8.61 Hz, 1H), 7.53-7.62 (m, 1H), 7.49 (s, 1H), 7.37 (d, J=8.61 Hz, 1H), 7.25-7.33 (m, 2H), 7.23 (dd, J=8.41, 4.69 Hz, 1H).

Workup

  1. concentrationconcentrated
  2. additionThe residue was diluted with CH2Cl2 and saturated NaHCO3 (aq.)
  3. additionwas added slowly
  4. extractionThe mixture was extracted with CH2Cl2 (3×)
  5. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-687e19d2e2df44da9e0b935bc40f7d7b
Source dataset
uspto-grants-2015_07
Patent number
US09090593B2

Reaction notes

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