Dimethylformamide → HCID 58420498, compound

HRID 601464Notes

Reaction equation

HRID 601464 reaction equation
[CH:1]1([N:4]2[C:13]3[C:8](=[CH:9][C:10]([F:17])=[C:11](F)[C:12]=3[O:14][CH3:15])[C:7](=[O:18])[C:6]([C:19]([O:21][CH2:22][CH3:23])=[O:20])=[C:5]2[S:24]([CH3:27])(=[O:26])=[O:25])[CH2:3][CH2:2]1.CC[N:30]([CH:34]([CH3:36])C)[CH:31]([CH3:33])C.C[N:38]([CH:40]=O)C.[CH3:42]COC(C)=O>>[NH2:38][C@H:40]([C@@H:36]1[CH2:33][CH2:31][N:30]([C:11]2[C:12]([O:14][CH3:15])=[C:13]3[C:8]([C:7](=[O:18])[C:6]([C:19]([O:21][CH2:22][CH3:23])=[O:20])=[C:5]([S:24]([CH3:27])(=[O:25])=[O:26])[N:4]3[CH:1]3[CH2:2][CH2:3]3)=[CH:9][C:10]=2[F:17])[CH2:34]1)[CH3:42]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 44226114HCID 44226114, compound2×

Product 1

HCID 58420498HCID 58420498, compound

Conditions

Temperature
70 °C

Procedure

A mixture containing compound (6) (16.7 g, 41.6 mmol), compound (10) (5.58 g, 48.9 mmol), anhydrous DIEA (20.8 g, 161 mmol, dried over 4 Å sieves), and anhydrous DMF (128 mL) is heated at 70° C. under an atmosphere of argon gas. After heating for 6 h (LC-MS analysis shows ˜7% compound (6) remained), the reaction mixture is cooled to room temperature, diluted with EtOAc (500 mL), and washed with water (500 mL). The aqueous layer is extracted with EtOAc (500 mL), and the combined organic layers are washed with a saturated aqueous solution of sodium bicarbonate (500 mL). The organic layer is diluted with water (500 mL) and treated with an aqueous solution of HCl (4 N) until the aqueous layer is acidic (pH 2-3 after shaking the mixture vigorously). The organic layer is separated, and this process is repeated. The combined aqueous layers are diluted with EtOAc (500 mL) and treated with an aqueous solution of sodium hydroxide (6 N) until the aqueous layer is basic (pH ˜8 after shaking the mixture vigorously). The aqueous layer is separated, and this process is repeated. The combined organic layers are dried over magnesium sulfate, filtered, and concentrated under reduced pressure giving an orange solid. Crude solid is used directly to next reaction.

Workup

  1. temperaturethe reaction mixture is cooled to room temperature
  2. washwashed with water (500 mL)
  3. extractionThe aqueous layer is extracted with EtOAc (500 mL)
  4. washthe combined organic layers are washed with a saturated aqueous solution of sodium bicarbonate (500 mL)
  5. additionThe organic layer is diluted with water (500 mL)
  6. additiontreated with an aqueous solution of HCl (4 N) until the aqueous layer
  7. customThe organic layer is separated
  8. additionThe combined aqueous layers are diluted with EtOAc (500 mL)
  9. additiontreated with an aqueous solution of sodium hydroxide (6 N) until the aqueous layer
  10. stirringafter shaking the mixture vigorously)
  11. customThe aqueous layer is separated
  12. dry with materialThe combined organic layers are dried over magnesium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated under reduced pressure
  15. customgiving an orange solid
  16. customCrude solid is used directly to next reaction

Sources & evidence

ORD record
ord-9ea382e4b9b14dc184f502376c75c490
Source dataset
uspto-grants-2011_03
Patent number
US07902365B2

Reaction notes

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