Morpholine → HCID 57657220, compound

HRID 244888Notes

Reaction equation

HRID 244888 reaction equation
CS(O[CH2:6][CH2:7][CH2:8][C:9]1[CH:10]=[CH:11][C:12]2[C:13]3[N:22]([CH2:23][C:24]([OH:27])([CH3:26])[CH3:25])[C:21]([CH2:28][O:29][CH2:30][CH3:31])=[N:20][C:14]=3[C:15]([NH2:19])=[N:16][C:17]=2[CH:18]=1)(=O)=O.[NH:32]1[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1>C(#N)C>[NH2:19][C:15]1[C:14]2[N:20]=[C:21]([CH2:28][O:29][CH2:30][CH3:31])[N:22]([CH2:23][C:24]([CH3:25])([OH:27])[CH3:26])[C:13]=2[C:12]2[CH:11]=[CH:10][C:9]([CH2:8][CH2:7][CH2:6][N:32]3[CH2:37][CH2:36][O:35][CH2:34][CH2:33]3)=[CH:18][C:17]=2[N:16]=1

Participants

4

Reactant 2

HCID 8083MorpholineHCID 86629394HCID 86629394, compound

Product 1

HCID 57657220HCID 57657220, compoundYield 42.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
75 °C

Procedure

A round bottom flask, equipped with a stir bar, was charged with 3-[4-amino-2-(ethoxymethyl)-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-7-yl]propyl methanesulfonate (0.24 g, 0.53 mmol) and acetonitrile (10 mL). Morpholine (0.23 g, 2.7 mmol) was added in one portion. The reaction mixture was heated at 75° C. for 18 hours and then cooled to ambient temperature. After concentrating under reduced pressure, the resulting solid was dissolved in dichloromethane (50 mL) and washed with saturated aqueous potassium carbonate (50 mL). The fractions were separated and the organic fraction was concentrated to dryness. The solid was purified by chromatography using a HORIZON HPFC system (silica cartridge, 0-25% CMA/chloroform). The material was further purified by a second chromatography treatment using a HORIZON HPFC system (silica cartridge, 10% methanol/dichloromethane). A final recrystallization from acetonitrile provided 0.1 g of 1-[4-amino-2-(ethoxymethyl)-7-(3-morpholin-4-ylpropyl)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol as a white crystalline solid, mp 132-133° C.

Workup

  1. customA round bottom flask, equipped with a stir bar
  2. temperaturecooled to ambient temperature
  3. concentrationAfter concentrating under reduced pressure
  4. dissolutionthe resulting solid was dissolved in dichloromethane (50 mL)
  5. washwashed with saturated aqueous potassium carbonate (50 mL)
  6. customThe fractions were separated
  7. concentrationthe organic fraction was concentrated to dryness
  8. customThe solid was purified by chromatography
  9. customThe material was further purified by a second chromatography treatment
  10. customA final recrystallization from acetonitrile

Sources & evidence

ORD record
ord-adf8eaf636a94a1aa5eeaa6fa14e1e5b
Source dataset
uspto-grants-2014_02
Patent number
US08658666B2

Reaction notes

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