1,2-Dimethoxyethane → HCID 57557304, compound

HRID 81917Notes

Reaction equation

HRID 81917 reaction equation
[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:22][OH:23])[N:14]([CH2:15][CH:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)[C:10]=2[C:9]2[CH:8]=[CH:7][C:6](Br)=[CH:5][C:4]=2[N:3]=1.[N:25]1([C:30]([C:32]2[CH:33]=[C:34](B(O)O)[CH:35]=[CH:36][CH:37]=2)=[O:31])[CH2:29][CH2:28][CH2:27][CH2:26]1.C(=O)([O-])[O-].[K+].[K+].C(COC)OC>O.C(#N)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:22][OH:23])[N:14]([CH2:15][CH:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)[C:10]=2[C:9]2[CH:8]=[CH:7][C:6]([C:36]3[CH:35]=[CH:34][CH:33]=[C:32]([C:30]([N:25]4[CH2:26][CH2:27][CH2:28][CH2:29]4)=[O:31])[CH:37]=3)=[CH:5][C:4]=2[N:3]=1

Participants

8

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 11430Potassium CarbonateHCID 113564283-(Pyrrolidine-1-carbonyl)phenylboronic acidHCID 67281118HCID 67281118, compound

Product 1

HCID 57557304HCID 57557304, compoundYield 20.6%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent

Procedure

To a mixture of [4-amino-7-bromo-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-2-yl]methanol (400 mg, 1.00 mmol), 3-pyrrolidinylcarbonyl phenyl boronic acid (328 mg, 1.50 mmol), potassium carbonate (455 mg, 3.30 mmol), dimethoxyethane (4 mL), and water (2 mL) under a nitrogen atmosphere was added Pd(PPh3)2Cl2 (14 mg, 0.02 mmol). The resulting suspension was refluxed for 18 hours. The reaction was cooled to ambient temperature. The reaction mixture was diluted with water and extracted with chloroform. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. Chromatography (SiO2, 0-40% CMA/CHCl3) gave material that was stirred in acetonitrile and filtered to provide 100 mg of [4-amino-7-[3-(pyrrolidin-1-ylcarbonyl)phenyl]-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-2-yl]methanol as a white powder, m.p. 281-284° C. MS (APCI) m/z 486.3 (M+H)+; Anal. calcd for C28H31N5O3: C, 69.26; H, 6.43; N, 14.42. Found: C, 68.99; H, 6.16; N, 14.46.

Workup

  1. temperatureThe resulting suspension was refluxed for 18 hours
  2. extractionextracted with chloroform
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customChromatography (SiO2, 0-40% CMA/CHCl3) gave material that
  7. filtrationfiltered

Sources & evidence

ORD record
ord-b412602c6be64478813c90825545f8d5
Source dataset
uspto-grants-2014_09
Patent number
US08846710B2

Reaction notes

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