Potassium Carbonate → HCID 46945564, compound

HRID 1047618Notes

Reaction equation

HRID 1047618 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]([NH:19][C@@H:20]([C:22]3[O:26][N:25]=[C:24]([CH3:27])[N:23]=3)[CH3:21])=[O:18])[S:14][C:11]=2[NH:12][N:13]=1.C(=O)([O-])[O-].[K+].[K+].I[CH2:35][CH2:36][OH:37]>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:19][C@@H:20]([C:22]3[O:26][N:25]=[C:24]([CH3:27])[N:23]=3)[CH3:21])=[O:18])[S:14][C:11]=2[N:12]([CH2:35][CH2:36][OH:37])[N:13]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 12225IodoethanolHCID 178434775HCID 178434775, compound

Product 1

HCID 46945564HCID 46945564, compoundYield 57.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

3-(2,4-Difluorophenyl)-N-[(1R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)ethyl]-1H-thieno[2,3-c]pyrazole-5-carboxamide (203.5 mg, 0.523 mmol) and potassium carbonate (331.5 mg, 2.40 mmol) were dissolved in N,N-dimethylformamide (5.20 ml) at 25° C. 2-Iodoethanol (69 μL, 0.885 mmol) was added. The reaction was heated to 50° C. and stirred for 4 h. The reaction was stopped, cooled to room temperature, quenched by addition of saturated aqueous ammonium chloride (10 mL), and extracted with ethyl acetate (3×15 mL). The combined organic phases were washed with saturated aqueous ammonium chloride (2×10 mL) and saturated aqueous sodium chloride (1×10 mL), dried (sodium sulfate), filtered, and the solvent evaporated under reduced pressure. The crude product was purified by flash chromatography (RediSep SiO2, 40 g column) on a CombiFlash purification system eluting with ethyl acetate-hexanes (0-100%). The title compound (129.6 mg, 0.299 mmol, 57.2% yield) was recovered as a light yellow/white solid. The undesired regioisomer, 3-(2,4-difluorophenyl)-2-(2-hydroxyethyl)-N-[(1R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)ethyl]-2H-indazole-6-carboxamide (33.1 mg, 0.076 mmol, 14.61% yield), was recovered as a light yellow/white solid. Title compound: HRMS [M+1] found=434.1091. 1H NMR (400 MHz, CDCl3): δ 7.99-7.89 (m, 1H); 7.61 (d, J=3.7 Hz, 1H); 7.01-6.91 (m, 2H); 6.80 (d, J=7.8 Hz, 1H); 5.60-5.51 (m, 1H); 4.39-4.34 (m, 2H); 4.15 (d, J=5.4 Hz, 2H); 2.90 (s, 1H); 2.40 (s, 3H); 1.70 (d, J=7.1 Hz, 3H). Regioisomer: HRMS [M+1] found 434.1095.

Workup

  1. temperaturecooled to room temperature
  2. customquenched by addition of saturated aqueous ammonium chloride (10 mL)
  3. extractionextracted with ethyl acetate (3×15 mL)
  4. washThe combined organic phases were washed with saturated aqueous ammonium chloride (2×10 mL) and saturated aqueous sodium chloride (1×10 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, 40 g column) on a CombiFlash purification system
  9. washeluting with ethyl acetate-hexanes (0-100%)

Sources & evidence

ORD record
ord-7518b0494a704489bad39f1b06faec63
Source dataset
uspto-grants-2013_10
Patent number
US08569512B2

Reaction notes

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