Cesium fluoride → HCID 58204194, compound

HRID 1849401Notes

Reaction equation

HRID 1849401 reaction equation
[CH:1]([N:4]1[C:8]([C:9]2[S:10][C:11]3[CH2:12][CH2:13][O:14][C:15]4[CH:22]=[CH:21][C:20]([C:23]5[C:24](=[O:29])[NH:25][CH:26]=[CH:27][CH:28]=5)=[CH:19][C:16]=4[C:17]=3[N:18]=2)=[N:7][CH:6]=[N:5]1)([CH3:3])[CH3:2].Br[CH2:31][CH2:32][O:33][CH3:34].[F-].[Cs+]>CN(C=O)C>[CH:1]([N:4]1[C:8]([C:9]2[S:10][C:11]3[CH2:12][CH2:13][O:14][C:15]4[CH:22]=[CH:21][C:20]([C:23]5[C:24]([O:29][CH2:31][CH2:32][O:33][CH3:34])=[N:25][CH:26]=[CH:27][CH:28]=5)=[CH:19][C:16]=4[C:17]=3[N:18]=2)=[N:7][CH:6]=[N:5]1)([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 25953Cesium fluoride2×HCID 809722-Bromoethyl methyl ether2×HCID 58203820HCID 58203820, compound

Product 1

HCID 58204194HCID 58204194, compoundYield 6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To 330 (0.075 g, 0.18 mmol) in DMF (2 mL) was added 1-bromo-2-methoxyethane (0.1 mL, 0.55 mmol) and cesium fluoride (0.084 g, 0.55 mmol). The reaction mixture was allowed to stir and heat at 80° C. for 2 days while monitoring by LCMS. To the reaction mixture was added bromo-2-methoxyethane (1 mL, 7.2 mmol) and cesium fluoride (1.0 g, 6.6 mmol). The reaction mixture was allowed to stir and heat at 80° C. for 2 days before cooling, concentrating under reduced pressure, and diluting with EtOAc. The solution was washed sequentially with water, and brine, before drying over MgSO4 and concentrating under reduced pressure. The crude material was dissolved in DMF and purified by reverse phase HPLC to provide 478 (5 mg, 6%). 1H NMR (400 MHz, DMSO) δ 8.60 (d, J=2.3, 1H), 8.16 (dd, J=4.9, 1.8, 1H), 8.10 (s, 1H), 7.80 (dd, J=7.4, 1.8, 1H), 7.59 (dd, J=8.4, 2.3, 1H), 7.13 (dd, J=7.7, 5.0, 2H), 5.73 (dt, J=13.1, 6.6, 1H), 4.51-4.38 (m, 4H), 3.70-3.58 (m, 2H), 3.48 (t, J=5.0, 2H), 3.18 (d, J=14.6, 3H), 1.55-1.46 (m, 6H). MS (ESI(+)): m/z 464.1 (M+H)

Workup

  1. stirringto stir
  2. temperatureheat at 80° C. for 2 days
  3. temperaturebefore cooling
  4. concentrationconcentrating under reduced pressure
  5. additiondiluting with EtOAc
  6. washThe solution was washed sequentially with water, and brine
  7. dry with materialbefore drying over MgSO4
  8. concentrationconcentrating under reduced pressure
  9. dissolutionThe crude material was dissolved in DMF
  10. custompurified by reverse phase HPLC

Sources & evidence

ORD record
ord-ee9d30f1480746ad82cb8c2816c52950
Source dataset
uspto-grants-2015_02
Patent number
US08952043B2

Reaction notes

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