Potassium Carbonate → HCID 10415222, compound

HRID 244530Notes

Reaction equation

HRID 244530 reaction equation
[CH3:1][O:2][C@@H:3]1[C@H:9]2[O:10][CH2:11][C@@H:12]([O:13]S(C)(=O)=O)[C@H:8]2[O:7][C@H:4]1[O:5][CH3:6].C(=O)([O-])[O-].[K+].[K+].FC(F)(F)C(O)=O.[Br:31][C:32]1[CH:37]=[CH:36][C:35]([NH:38][C:39]2[C:48]3[C:43](=[CH:44][C:45](O)=[C:46]([O:49][CH3:50])[CH:47]=3)[N:42]=[CH:41][N:40]=2)=[CH:34][C:33]=1[Cl:52]>CN(C=O)C.C(OCC)(=O)C>[Br:31][C:32]1[CH:37]=[CH:36][C:35]([NH:38][C:39]2[C:48]3[C:43](=[CH:44][C:45]([O:13][C@H:12]4[CH2:11][O:10][C@@H:9]5[C@@H:3]([O:2][CH3:1])[C@@H:4]([O:7][C@H:8]45)[O:5][CH3:6])=[C:46]([O:49][CH3:50])[CH:47]=3)[N:42]=[CH:41][N:40]=2)=[CH:34][C:33]=1[Cl:52]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 86637230HCID 86637230, compoundHCID 136335139HCID 136335139, compound

Product 1

HCID 10415222HCID 10415222, compoundYield 28%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
135 °C

Procedure

Methyl 3,6-anhydro-2-O-methyl-5-O-(methylsulfonyl)-β-D-glucofuranoside (314 mg, 1.1 mmol) was dissolved in DMF (3 mL). To this solution was added potassium carbonate (404 mg, 2.9 mmol) and 4-[(4-bromo-3-chlorophenyl)amino]-6-methyloxy-7-hydroxyquinazoline trifluoroacetate (280 mg, 0.59 mmol). The resulting mixture was heated at 135° C. for 18 h. After cooling to room temperature the reaction mixture was diluted with ethyl acetate (15 mL), washed with water, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by flash chromatography (silica gel, 2-7% methanol in 1:1 ethyl acetate:hexanes) to give methyl 3,6-anhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-O-methyl-α-L-idofuranoside as a white solid, 181 mg, 28% yield. 1H NMR (400 MHz; Methanol-d4): 8.75 (s, 1H), 8.04-8.06 (d, 1H), 7.99 (s, 1H), 7.78-7.75 (d, 1H), 7.64-7.61 (d, 1H), 7.35 (s, 1H), 5.16-5.14 (d, 1H), 5.02 (s, 1H), 4.89 (br, 1H), 4.69-4.68 (d, 1H) 4.46-4.42 (dd, 1H), 4.09 (br, 1H), 4.06 (s, 3H), 3.69 (s, 1H), 3.48 (s, 3H), 3.42 (s, 3H); MS (EI) for C23H23BrClN3O6: 551.88 (MH+).

Workup

  1. temperatureAfter cooling to room temperature the reaction mixture
  2. washwashed with water
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography (silica gel, 2-7% methanol in 1:1 ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-913293e6b9d240759cf603170f41b362
Source dataset
uspto-grants-2014_02
Patent number
US08658654B2

Reaction notes

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