Tetrahydrofuran → HCID 44470370, compound

HRID 2382956Notes

Reaction equation

HRID 2382956 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][NH:9][C:10]([C:12]2[C:13]3[CH:14]=[N:15][N:16]([C:21]4[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=4)[C:17]=3[CH:18]=[CH:19][CH:20]=2)=[O:11])=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[CH3:37][S:38](Cl)(=[O:40])=[O:39].CCCC[N+](CCCC)(CCCC)CCCC.[F-].C1COCC1>ClCCl>[CH3:37][S:38]([NH:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][NH:9][C:10]([C:12]2[C:13]3[CH:14]=[N:15][N:16]([C:21]4[CH:22]=[CH:23][C:24]([F:27])=[CH:25][CH:26]=4)[C:17]=3[CH:18]=[CH:19][CH:20]=2)=[O:11])=[CH:4][CH:3]=1)(=[O:40])=[O:39]

Participants

7

Reactant 5

HCID 8028TetrahydrofuranHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 2724141Tetrabutylammonium FluorideHCID 58138817HCID 58138817, compound

Product 1

HCID 44470370HCID 44470370, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 1-(4-fluoro-phenyl)-1H-indazole-4-carboxylic acid (6-amino-pyridin-3-ylmethyl)-amide (40.0 mg, 0.111 mmol) in dichloromethane (1.0 mL) was added DIEA (0.15 mL, 0.89 mmol). The solution was cooled to 0° C., treated with methanesulfonyl chloride (0.021 mL, 0.28 mmol), and gradually allowed to warm to room temperature. The solution was diluted CH2Cl2 (20 mL) and washed with saturated aqueous NH4Cl (3×10 mL), saturated aqueous NaHCO3 (10 mL) and brine (10 mL). The organic layer was dried over MgSO4, filtered and concentrated. The crude mixture was diluted with THF (0.5 mL) and a 1 M solution of TBAF in THF (1.0 mL, 1.0 mmol) was added. The solution was warmed at reflux for 6 hours. The solution was cooled to room temperature and quenched with saturated aqueous NH4Cl (15 mL), diluted with ethyl acetate (15 mL), and washed with NaHCO3 (10 mL) and brine (10 mL). The organic layer was dried over MgSO4, filtered and concentrated. The residue was purified by silica gel chromatography, eluting with a gradient of 0-10% MeOH in CH2Cl2 to afford the title compound as a solid.

Workup

  1. temperatureto warm to room temperature
  2. washwashed with saturated aqueous NH4Cl (3×10 mL), saturated aqueous NaHCO3 (10 mL) and brine (10 mL)
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. additionThe crude mixture was diluted with THF (0.5 mL)
  7. temperatureThe solution was warmed
  8. temperatureat reflux for 6 hours
  9. temperatureThe solution was cooled to room temperature
  10. customquenched with saturated aqueous NH4Cl (15 mL)
  11. additiondiluted with ethyl acetate (15 mL)
  12. washwashed with NaHCO3 (10 mL) and brine (10 mL)
  13. dry with materialThe organic layer was dried over MgSO4
  14. filtrationfiltered
  15. concentrationconcentrated
  16. customThe residue was purified by silica gel chromatography
  17. washeluting with a gradient of 0-10% MeOH in CH2Cl2

Sources & evidence

ORD record
ord-bb3ba80dbbe044d0873b52cdebaf856a
Source dataset
uspto-grants-2012_09
Patent number
US08263597B2

Reaction notes

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