Imidazole → 6-((3-(4-(difluoromethoxy)benzylamino)isoxazol-5-yl)methoxy)quinolin-2(1H)-one

HRID 1023185Notes

Reaction equation

HRID 1023185 reaction equation
[F:1][CH:2]([F:30])[O:3][C:4]1[CH:29]=[CH:28][C:7]([CH2:8][NH:9][C:10]2[CH2:14][CH:13]([CH2:15][O:16][C:17]3[CH:18]=[C:19]4[C:24](=[CH:25][CH:26]=3)[NH:23][C:22](=[O:27])[CH2:21][CH2:20]4)[O:12][N:11]=2)=[CH:6][CH:5]=1.N1C=CN=C1.II>C1(C)C=CC=CC=1.C(OCC)(=O)C>[F:30][CH:2]([F:1])[O:3][C:4]1[CH:5]=[CH:6][C:7]([CH2:8][NH:9][C:10]2[CH:14]=[C:13]([CH2:15][O:16][C:17]3[CH:18]=[C:19]4[C:24](=[CH:25][CH:26]=3)[NH:23][C:22](=[O:27])[CH:21]=[CH:20]4)[O:12][N:11]=2)=[CH:28][CH:29]=1

Participants

6

Reactant 3

HCID 795ImidazoleHCID 807IodineHCID 178515696HCID 178515696, compound

Product 1

HCID 715420406-((3-(4-(difluoromethoxy)benzylamino)isoxazol-5-yl)methoxy)quinolin-2(1H)-oneYield 23%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

Into a sealed tube was placed a solution of 6-((3-((4-(difluoromethoxy)benzyl)amino)-4,5-dihydroisoxazol-5-yl)methoxy)-3,4-dihydroquinolin-2(1H)-one (0.12 g, 0.287 mmol), imidazole (0.117 g, 1.725 mmol), and iodine (0.219 g, 0.862 mmol) in toluene (5 mL). The tube was sealed and heated at 110° C. for 24 h. The reaction mixture was diluted with ethyl acetate, washed with 10% Na2S2O4 and brine, dried over Na2SO4, and concentrated. The crude product was purified by preparative HPLC on an Xbridge phenyl column (150×19×5μ) using a 10 mM NH4OAc/ACN gradient (0-100%) to give 6-((3-(4-(difluoromethoxy)benzylamino)isoxazol-5-yl)methoxy)quinolin-2(1H)-one as a white solid (0.023 g, 23%). 1HNMR: 400 MHz, DMSO-d6: δ 4.24 (d, J=6.00 Hz, 2H), 5.11 (s, 2H), 6.06 (s, 1H), 6.51 (d, J=9.20 Hz, 1H), 6.73 (t, J=6.00 Hz, 1H), 7.01-7.39 (m, 8H), 7.83 (d, J=9.60 Hz, 1H), 11.66 (s, 1H). LCMS: RT 1.558 min; LCMS (ES-API), m/z 412.0 (M−H).

Workup

  1. customInto a sealed tube was placed
  2. customThe tube was sealed
  3. washwashed with 10% Na2S2O4 and brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe crude product was purified by preparative HPLC on an Xbridge phenyl column (150×19×5μ)

Sources & evidence

ORD record
ord-7c9062a09fa24ed9b2fdaa41d932ba82
Source dataset
uspto-grants-2014_05
Patent number
US08722670B2

Reaction notes

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