Thionyl Chloride → HCID 45110759, compound

HRID 386905Notes

Reaction equation

HRID 386905 reaction equation
[CH:1]1([CH2:4][S:5]([C:8]([CH3:13])([CH3:12])[C:9]([OH:11])=O)(=[O:7])=[O:6])[CH2:3][CH2:2]1.S(Cl)(Cl)=O.C(N(CC)C(C)C)(C)C.[CH2:27]([N:29]1[C:33]([C:34]2[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=2)=[N:32][C:31]([NH2:42])=[N:30]1)[CH3:28]>C(Cl)Cl>[CH:1]1([CH2:4][S:5]([C:8]([CH3:13])([CH3:12])[C:9]([NH:42][C:31]2[N:32]=[C:33]([C:34]3[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=3)[N:29]([CH2:27][CH3:28])[N:30]=2)=[O:11])(=[O:6])=[O:7])[CH2:2][CH2:3]1

Participants

6

Reactant 4

HCID 24386Thionyl ChlorideHCID 81531DiisopropylethylamineHCID 59253172HCID 59253172, compoundHCID 59253257HCID 59253257, compound

Product 1

HCID 45110759HCID 45110759, compoundYield 92.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Activation of 0.43 g (2.09 mmol) of 2-cyclopropylmethanesulfonyl-2-methyl-propionic acid as the corresponding acid chloride is achieved by treatment with thionyl chloride (3 mL) at 50° C. for 3 h. The reaction is cooled to room temperature and excess thionyl chloride is removed under reduced pressure. The crude acid chloride is dissolved in THF (5 mL) and N,N-diisopropylethylamine (0.39 mL, 2.25 mmol) solution is added followed by 0.30 g (1.38 mmol) of 1-ethyl-5-(4-methoxy-phenyl)-1H-[1,2,4]triazol-3-ylamine. After complete addition the reaction is heated to 70° C. for 18 h. The reaction is cooled to room temperature and the reaction mixture is diluted with DCM (20 mL) and washed with saturated aqueous NaHCO3 solution (20 mL). The combined organic layers are dried over Na2SO4, filtered and the filtrate is concentrated under reduced pressure. The residue is slurried in DCM/ether (1/1, 10 mL) to yield 0.52 g of 2-cyclopropylmethanesulfonyl-N-[1-ethyl-5-(4-methoxy-phenyl)-1H-[1,2,4]triazol-3-yl]-2-methyl-propionamide. Yield: 92%; ES-MS: m/z 407 [M+H].

Workup

  1. customexcess thionyl chloride is removed under reduced pressure
  2. dissolutionThe crude acid chloride is dissolved in THF (5 mL)
  3. additionAfter complete addition the reaction
  4. temperatureis heated to 70° C. for 18 h
  5. temperatureThe reaction is cooled to room temperature
  6. washwashed with saturated aqueous NaHCO3 solution (20 mL)
  7. dry with materialThe combined organic layers are dried over Na2SO4
  8. filtrationfiltered
  9. concentrationthe filtrate is concentrated under reduced pressure

Sources & evidence

ORD record
ord-0a684fd0f38d4acf938025fe094e4324
Source dataset
uspto-grants-2013_02
Patent number
US08372874B2

Reaction notes

Loading…