Morpholine → HCID 66571344, compound

HRID 82008Notes

Reaction equation

HRID 82008 reaction equation
[CH3:1][C:2]1[C:6]([C:7]2[C:8]([O:29][CH3:30])=[CH:9][C:10]3[C:11]4[N:19]([C@@H:20]([C:22]5[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=5)[CH3:21])[C:18](=O)[NH:17][C:12]=4[CH:13]=[N:14][C:15]=3[CH:16]=2)=[C:5]([CH3:31])[O:4][N:3]=1.O=P(Cl)(Cl)Cl.[NH:37]1[CH2:42][CH2:41][O:40][CH2:39][CH2:38]1>CN1C(=O)CCC1.CS(C)=O>[CH3:1][C:2]1[C:6]([C:7]2[C:8]([O:29][CH3:30])=[CH:9][C:10]3[C:11]4[N:19]([C@@H:20]([C:22]5[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=5)[CH3:21])[C:18]([N:37]5[CH2:42][CH2:41][O:40][CH2:39][CH2:38]5)=[N:17][C:12]=4[CH:13]=[N:14][C:15]=3[CH:16]=2)=[C:5]([CH3:31])[O:4][N:3]=1

Participants

6

Reactant 3

HCID 8083MorpholineHCID 24813Phosphorus oxychlorideHCID 529351837-(3,5-Dimethyl-4-isoxazolyl)-8-(methyloxy)-1-[(1R)-1-phenylethyl]-1,3-dihydro-2H-imidazo[4,5-c]quinolin-2-one

Product 1

HCID 66571344HCID 66571344, compoundYield 0.75%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
100 °C

Procedure

7-(3,5-Dimethyl-4-isoxazolyl)-8-(methyloxy)-1-[(1R)-1-phenylethyl]-1,3-dihydro-2H-imidazo[4,5-c]quinolin-2-one (for a preparation see Intermediate 11) (0.16 g, 0.386 mmol) was dissolved in POCl3 (1 ml, 10.73 mmol) and heated at 100° C. for 3 days. The reaction mixture was evaporated in vacuo to give a black gum. The residue was dissolved in NMP (2 ml) and morpholine (2 ml, 22.96 mmol) was added, then the solution was heated in the microwave at 150° C. for 1 h. The reaction mixture was loaded onto a 20 g SCX-2 cartridge and washed through with methanol (40 ml), then eluted with 2M methanolic ammonia and the eluant evaporated in vacuo to give an amber oil. This was dissolved in DMSO (1 ml) and purified by MDAP (HpH) to give 7-(3,5-dimethyl-4-isoxazolyl)-8-(methyloxy)-2-(4-morpholinyl)-1-[(1R)-1-phenylethyl]-1H-imidazo[4,5-c]quinoline (1.4 mg, 2.90 μmol, 0.750% yield). LCMS (formate) Rt 0.86 min, MH+ 484

Workup

  1. customThe reaction mixture was evaporated in vacuo
  2. customto give a black gum
  3. temperaturethe solution was heated in the microwave at 150° C. for 1 h
  4. washwashed through with methanol (40 ml)
  5. washeluted with 2M methanolic ammonia
  6. customthe eluant evaporated in vacuo
  7. customto give an amber oil
  8. custompurified by MDAP (HpH)

Sources & evidence

ORD record
ord-f52e2b1e01ab4a919fbdee63e3d1f7ab
Source dataset
uspto-grants-2014_09
Patent number
US08846709B2

Reaction notes

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