Hydrochloric Acid → 1-(1-(2-Morpholinoethyl)-1H-indazol-5-yl)-4-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-one

HRID 2390436Notes

Reaction equation

HRID 2390436 reaction equation
[O:1]=[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=2)[CH:5]=[CH:4][N:3]1[C:18]1[CH:19]=[C:20]2[C:24](=[CH:25][CH:26]=1)[N:23]([CH2:27][CH:28]=O)[N:22]=[CH:21]2.[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1.Cl.C([O-])(O)=O.[Na+]>C(Cl)Cl.CO.CC(O)=O>[O:33]1[CH2:34][CH2:35][N:30]([CH2:28][CH2:27][N:23]2[C:24]3[C:20](=[CH:19][C:18]([N:3]4[CH:4]=[CH:5][C:6]([C:8]5[CH:9]=[CH:10][C:11]([C:14]([F:15])([F:17])[F:16])=[CH:12][CH:13]=5)=[CH:7][C:2]4=[O:1])=[CH:26][CH:25]=3)[CH:21]=[N:22]2)[CH2:31][CH2:32]1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 8083MorpholineHCID 516892Sodium BicarbonateHCID 576254982-(5-(2-Oxo-4-(4-(trifluoromethyl)phenyl)pyridin-1(2H)-yl)-1H-indazol-1-yl)acetaldehyde

Product 1

HCID 252058311-(1-(2-Morpholinoethyl)-1H-indazol-5-yl)-4-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-oneYield 33.5%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(5-(2-oxo-4-(4-(trifluoromethyl)phenyl)pyridin-1(2H)-yl)-1H-indazol-1-yl)acetaldehyde (84 mg, 0.21 mmol) in CH2Cl2 (4.0 mL), MeOH (1.0 mL) and AcOH (0.50 mL) was added morpholine (0.06 mL, 0.7 mmol) and picoline-borane complex (25 mg, 0.23 mmol). After stirring at ambient temperature under nitrogen atmosphere for 1.5 h, the solution was treated with 1 N HCl (10.0 mL) and stirred vigorously for 30 minutes. The mixture was made basic with saturated aqueous NaHCO3 (25 mL) and extracted with CH2Cl2 (3×25 mL). The organics were dried over Na2SO4, filtered and concentrated to dryness. Purification by flash chromatography (silica gel, CH2Cl2/MeOH, 97:3) gave the title compound (33 mg, 33%) as an off-white solid: 1H NMR (500 MHz, CDCl3) δ 8.14 (d, J=0.7 Hz, 1H), 7.95 (d, J=8.1 Hz, 2H), 7.85-7.77 (m, 5H), 7.48 (dd, J=8.9, 1.9 Hz, 1H), 6.95 (d, J=1.8 Hz, 1H), 6.85 (dd, J=7.1, 2.0 Hz, 1H), 4.63 (t, J=6.5 Hz, 2H), 3.64-3.62 (m, 4H), 2.91 (t, J=6.5 Hz, 2H), 2.54-2.52 (m, 4H); ESI MS m/z 469 [M+H]+.

Workup

  1. stirringstirred vigorously for 30 minutes
  2. extractionextracted with CH2Cl2 (3×25 mL)
  3. dry with materialThe organics were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated to dryness
  6. customPurification by flash chromatography (silica gel, CH2Cl2/MeOH, 97:3)

Sources & evidence

ORD record
ord-2b13dc3f304f4299959c93c1856edff0
Source dataset
uspto-grants-2012_09
Patent number
US08273770B2

Reaction notes

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