Morpholine → HCID 66571408, compound

HRID 82010Notes

Reaction equation

HRID 82010 reaction equation
[CH3:1][C:2]1[C:6]([C:7]2[C:8]([O:28][CH3:29])=[CH:9][C:10]3[C:11]4[N:19]([CH2:20][CH:21]5[CH2:26][CH2:25][O:24][CH2:23][CH2:22]5)[C:18](=O)[NH:17][C:12]=4[CH:13]=[N:14][C:15]=3[CH:16]=2)=[C:5]([CH3:30])[O:4][N:3]=1.O=P(Cl)(Cl)Cl.P(Cl)(Cl)(Cl)(Cl)Cl.[NH:42]1[CH2:47][CH2:46][O:45][CH2:44][CH2:43]1>CN1C(=O)CCC1.C(Cl)Cl>[CH3:1][C:2]1[C:6]([C:7]2[C:8]([O:28][CH3:29])=[CH:9][C:10]3[C:11]4[N:19]([CH2:20][CH:21]5[CH2:22][CH2:23][O:24][CH2:25][CH2:26]5)[C:18]([N:42]5[CH2:47][CH2:46][O:45][CH2:44][CH2:43]5)=[N:17][C:12]=4[CH:13]=[N:14][C:15]=3[CH:16]=2)=[C:5]([CH3:30])[O:4][N:3]=1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 24813Phosphorus oxychlorideHCID 24819Phosphorus pentachlorideHCID 709802207-(3,5-Dimethyl-4-isoxazolyl)-8-(methyloxy)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-c]quinolin-2-one

Product 1

HCID 66571408HCID 66571408, compoundYield 1.827%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
120 °C

Procedure

7-(3,5-Dimethyl-4-isoxazolyl)-8-(methyloxy)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-c]quinolin-2-one (220 mg, 0.539 mmol) (for a preparation see intermediate 14) was dissolved in POCl3 (2 ml, 21.46 mmol), PCl5 (0.2 g, 0.960 mmol) was added and the mixture was heated at 120° C. for 24 h. The reaction mixture was evaporated in vacuo to give a beige solid. The solid was dissolved in NMP (0.5 ml) and morpholine (0.3 ml, 3.44 mmol) was added, then the solution was heated in the microwave at 150° C. for 1 h. The solution was loaded onto a 20 g SCX-2 cartridge and washed with methanol (30 ml), then eluted with 2M methanolic ammonia (30 ml) and the eluant evaporated in vacuo to give a beige gum. This was dissolved in DCM (3 ml) and loaded onto a 25 g silica column, then eluted with 2M methanolic ammonia/DCM (0-10%, 25 column volumes) and product containing fractions were evaporated in vacuo to give 7-(3,5-dimethyl-4-isoxazolyl)-8-(methyloxy)-2-(4-morpholinyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinoline (4.7 mg, 9.84 μmol, 1.827% yield) as a beige solid. LCMS (formate) Rt 0.70 min, MH+ 478

Workup

  1. customThe reaction mixture was evaporated in vacuo
  2. customto give a beige solid
  3. temperaturethe solution was heated in the microwave at 150° C. for 1 h
  4. washwashed with methanol (30 ml)
  5. washeluted with 2M methanolic ammonia (30 ml)
  6. customthe eluant evaporated in vacuo
  7. customto give a beige gum
  8. washeluted with 2M methanolic ammonia/DCM (0-10%, 25 column volumes) and product
  9. additioncontaining fractions
  10. customwere evaporated in vacuo

Sources & evidence

ORD record
ord-5d23277468bf427e9715b7ee60a7d72f
Source dataset
uspto-grants-2014_09
Patent number
US08846709B2

Reaction notes

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