4-Methylmorpholine → HCID 178434775, compound

HRID 1047617Notes

Reaction equation

HRID 1047617 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[C:10]2[CH:16]=[C:15]([C:17]([OH:19])=O)[S:14][C:11]=2[NH:12][N:13]=1.Cl.C[N:22](C)CCCN=C=NCC.[OH:32][N:33]1[C:37]2[N:38]=[CH:39][CH:40]=[CH:41][C:36]=2N=N1.CN1CCOCC1>CN(C)C=O>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[C:10]2[CH:16]=[C:15]([C:17]([NH:22][C@@H:40]([C:39]3[O:32][N:33]=[C:37]([CH3:36])[N:38]=3)[CH3:41])=[O:19])[S:14][C:11]=2[NH:12][N:13]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 178524022HCID 178524022, compound

Product 1

HCID 178434775HCID 178434775, compoundYield 150%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

3-(2,4-Difluorophenyl)-1H-thieno[2,3-c]pyrazole-5-carboxylic acid (964.9 mg, 1.877 mmol, with 4 equivalents of sodium chloride), L-(1R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)ethanamine bis-hydrochloride (462.3 mg, 2.311 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (725.4 mg, 3.78 mmol), 1-hydroxy-7-azabenzotriazole (129.6 mg, 0.952 mmol), and N-methylmorpholine (0.826 mL, 7.51 mmol) were dissolved in N,N-dimethylformamide (18 mL) at 25° C. The reaction mixture was heated to 50° C. and allowed to stir for 10 min. The reaction was stopped, cooled to room temperature, quenched by addition of saturated aqueous ammonium chloride (15 mL), and extracted with ethyl acetate (3×15 mL). The combined organic phases were washed with saturated aqueous ammonium chloride (2×15 mL) and saturated aqueous sodium chloride (1×15 mL), dried (sodium sulfate), filtered, and the solvent evaporated under reduced pressure. The crude product was purified by flash chromatography (RediSep SiO2, 120 g column) on a CombiFlash purification system eluting with ethyl acetate-hexanes (0-100%). The title compound (556.0 mg, 1.428 mmol, 76% yield) was recovered as a light yellow/white solid. LC-MS [M-1-1]=390.2

Workup

  1. temperaturecooled to room temperature
  2. customquenched by addition of saturated aqueous ammonium chloride (15 mL)
  3. extractionextracted with ethyl acetate (3×15 mL)
  4. washThe combined organic phases were washed with saturated aqueous ammonium chloride (2×15 mL) and saturated aqueous sodium chloride (1×15 mL)
  5. dry with materialdried (sodium sulfate)
  6. filtrationfiltered
  7. customthe solvent evaporated under reduced pressure
  8. customThe crude product was purified by flash chromatography (RediSep SiO2, 120 g column) on a CombiFlash purification system
  9. washeluting with ethyl acetate-hexanes (0-100%)

Sources & evidence

ORD record
ord-9806487fe38a4c5a9f31f9ad396269bd
Source dataset
uspto-grants-2013_10
Patent number
US08569512B2

Reaction notes

Loading…