Cesium carbonate → HCID 59393681, compound

HRID 2092141Notes

Reaction equation

HRID 2092141 reaction equation
[CH3:1][S:2][CH2:3]Cl.[CH3:5][C:6]([C:26]1[CH:31]=[CH:30][C:29]([C:32]2[CH:33]=[C:34]([OH:38])[CH:35]=[N:36][CH:37]=2)=[CH:28][CH:27]=1)([C:10]1[CH:15]=[CH:14][C:13]([C:16]2[N:17]=[N:18][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:20][CH:21]=2)=[CH:12][N:11]=1)[CH:7]([CH3:9])[CH3:8].C(=O)([O-])[O-].[Cs+].[Cs+].OS([O-])(=O)=O.[Na+]>CN(C=O)C>[CH3:5][C:6]([C:10]1[N:11]=[CH:12][C:13]([C:16]2[N:17]=[N:18][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:20][CH:21]=2)=[CH:14][CH:15]=1)([C:26]1[CH:27]=[CH:28][C:29]([C:32]2[CH:37]=[N:36][CH:35]=[C:34]([O:38][CH2:3][S:2][CH3:1])[CH:33]=2)=[CH:30][CH:31]=1)[CH:7]([CH3:9])[CH3:8]

Participants

6

Reactant 4

HCID 10796Cesium carbonate2×HCID 16916Chloromethyl methyl sulfide2×HCID 516919Sodium BisulfateHCID 59393688HCID 59393688, compound

Product 1

HCID 59393681HCID 59393681, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

Chloromethyl methyl sulfide (12.0 μL, 0.140 mmol) was added to a stirred suspension of 6a (42.0 mg, 0.0910 mmol) and cesium carbonate (46.0 mg, 0.140 mmol) in DMF (2.00 mL) at rt, and the resulting mixture was heated at 40° C. for approximately 2 h. The reaction mixture was cooled to rt, and second portions of cesium carbonate (46.0 mg, 0.140 mmol) and chloromethyl methyl sulfide (12.0 μL, 0.140 mmol) were added. The resulting mixture was heated at 40° C. for about another 3 h. After cooling to rt, the reaction mixture was poured into 10% aqueous sodium hydrosulfate and extracted three times with diethyl ether. The combined organic extracts were washed with water and brine, dried (sodium sulfate) and concentrated in vacuo. Purification of the crude residue by flash chromatography on silica gel (gradient elution; 20%-50% EtOAc/hexanes as eluent) afforded the title compound 6b. m/z (ES) 525 (MH)+ 1HNMR (500 MHz, CDCl3): δ 9.28 (d, 1H, J=2.1 Hz), 8.51 (br, 1H), 8.45 (dd, 1H, J=2.4, 8.3 Hz), 8.32 (br, 1H), 8.07 (d, 1H, J=8.9 Hz), 7.92 (d, 1H, J=9.0 Hz), 7.55 (m, 6H), 5.25 (s, 2H), 3.21 (m, 1H), 2.28 (s, 3H), 1.81 (s, 3H), 0.93 (d, 3H, J=6.4 Hz), 0.89 (d, 3H, J=6.6 Hz).

Workup

  1. temperatureThe reaction mixture was cooled to rt
  2. temperatureThe resulting mixture was heated at 40° C. for about another 3 h
  3. temperatureAfter cooling to rt
  4. extractionextracted three times with diethyl ether
  5. washThe combined organic extracts were washed with water and brine
  6. dry with materialdried (sodium sulfate)
  7. concentrationconcentrated in vacuo
  8. customPurification of the crude residue by flash chromatography on silica gel (gradient elution; 20%-50% EtOAc/hexanes as eluent)

Sources & evidence

ORD record
ord-e0be2280d0894f11bdceb370409a048c
Source dataset
uspto-grants-2013_05
Patent number
US08440672B2

Reaction notes

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