Dimethylformamide → 2-(methoxymethyl)-8-(2-oxo-2-thiomorpholin-4-ylethoxy)-1-propyl-1H-imidazo[4,5-c]quinolin-amine

HRID 540936Notes

Reaction equation

HRID 540936 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:8][C:9]([N:11]1[CH2:16][CH2:15][S:14][CH2:13][CH2:12]1)=[O:10].[OH:17][C:18]1[CH:27]=[CH:26][C:25]2[N:24]=[C:23](N)[C:22]3[N:29]=[C:30]([CH2:35][O:36][CH3:37])[N:31]([CH2:32][CH2:33][CH3:34])[C:21]=3[C:20]=2[CH:19]=1.C[N:39](C=O)C>>[CH3:37][O:36][CH2:35][C:30]1([NH2:39])[NH:29][C:22]2[CH:23]=[N:24][C:25]3[CH:26]=[CH:27][C:18]([O:17][CH2:8][C:9](=[O:10])[N:11]4[CH2:16][CH2:15][S:14][CH2:13][CH2:12]4)=[CH:19][C:20]=3[C:21]=2[N:31]1[CH2:32][CH2:33][CH3:34]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 404242984-(Bromoacetyl) thiomorpholineHCID 689723708-hydroxy-2-methoxymethyl-1-propyl-1H-imidazo[4,5-c]quinolin-4-amine

Product 1

HCID 695070122-(methoxymethyl)-8-(2-oxo-2-thiomorpholin-4-ylethoxy)-1-propyl-1H-imidazo[4,5-c]quinolin-amine

Conditions

Temperature
70 °C

Procedure

Cesium carbonate (1.7 g, 5.22 mmol, 3 eq) was added to a mixture of 4-(bromoacetyl)thiomorpholine (468 mg, 2.09 mmol, 1.2 eq, prepared according to the method described in Part C of Example 30) and 8-hydroxy-2-methoxymethyl-1-propyl-1H-imidazo[4,5-c]quinolin-4-amine (500 mg, 1.74 mmol, 1.0 eq) in 20 mL of DMF. The reaction mixture was heated to 70° C. and maintained for 14 hours. The reaction mixture was then cooled to ambient temperature, filtered, diluted with 50 mL of dichloromethane, concentrated under reduced pressure, and filtered to afford crude material. The crude material was purified by chromatography on a HORIZON HPFC system (eluting with a gradient of methanol/dichloromethane (20:80) in dichloromethane from 0:100 to 40:60), concentrated under reduced pressure, and crystallized from acetonitrile to afford 231 mg of 2-(methoxymethyl)-8-(2-oxo-2-thiomorpholin-4-ylethoxy)-1-propyl-1H-imidazo[4,5-c]quinolin-amine as an off white solid, mp 214-216° C.

Workup

  1. customprepared
  2. temperaturemaintained for 14 hours
  3. temperatureThe reaction mixture was then cooled to ambient temperature
  4. filtrationfiltered
  5. additiondiluted with 50 mL of dichloromethane
  6. concentrationconcentrated under reduced pressure
  7. filtrationfiltered
  8. customto afford crude material
  9. customThe crude material was purified by chromatography on a HORIZON HPFC system (
  10. washeluting with a gradient of methanol/dichloromethane (20:80) in dichloromethane from 0:100 to 40:60),
  11. concentrationconcentrated under reduced pressure
  12. customcrystallized from acetonitrile

Sources & evidence

ORD record
ord-8130de8e869143b286ec0c29874b29d6
Source dataset
uspto-grants-2014_10
Patent number
US08871782B2

Reaction notes

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