Potassium Acetate → HCID 66731067, compound

HRID 1028017Notes

Reaction equation

HRID 1028017 reaction equation
[F:1][C:2]([F:34])([F:33])[C@H:3]([NH:5][S:6]([C:9]1[CH:10]=[N:11][C:12]([C:15]2[N:16]([CH:28]3[CH2:32][CH2:31][CH2:30][CH2:29]3)[C:17]3[C:22]([C:23]=2[C:24]#[N:25])=[CH:21][C:20](Br)=[C:19]([CH3:27])[CH:18]=3)=[CH:13][CH:14]=1)(=[O:8])=[O:7])[CH3:4].B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)[O:36]1.C([O-])(=O)C.[K+]>O1CCOCC1.C(OCC)(=O)C>[F:1][C:2]([F:34])([F:33])[C@H:3]([NH:5][S:6]([C:9]1[CH:10]=[N:11][C:12]([C:15]2[N:16]([CH:28]3[CH2:32][CH2:31][CH2:30][CH2:29]3)[C:17]3[C:22]([C:23]=2[C:24]#[N:25])=[CH:21][C:20]([OH:36])=[C:19]([CH3:27])[CH:18]=3)=[CH:13][CH:14]=1)(=[O:8])=[O:7])[CH3:4]

Participants

6

Reactant 3

HCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 66730892HCID 66730892, compound

Product 1

HCID 66731067HCID 66731067, compoundYield 84%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of (R)-6-(5-bromo-3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-pyridine-3-sulfonic acid (2,2,2-trifluoro-1-methyl-ethyl)-amide (0.54 g, 0.97 mmol), bis(pinacolato)diboron (0.5 g, 2.0 mmol), PdCl2dppf-CH2Cl2 complex (16 mg, 0.02 mmol) and potassium acetate (0.40 g, 4.0 mmol) in dioxane (5 mL) was stirred at 80° C. overnight. The mixture was then cooled to room temperature, diluted with ethyl acetate and filtered through a silica-celite pad. The filtrate was concentrated, dissolved in acetone (10 mL) and cooled to 0° C. Into this solution was added an aqueous solution of Oxone (10 mL, 1.0 M). The mixture was stirred at room temperature for 15 min and diluted with ethyl acetate and water. The aqueous layer was extracted with ethyl acetate. The organic extractions were combined and washed with aq. NaHSO3 and brine, dried over Na2SO4, and concentrated. Purification on silica gel eluting with 40% ethyl acetate in hexane gave (R)-6-(3-cyano-1-cyclopentyl-5-hydroxy-6-methyl-1H-indol-2-yl)-pyridine-3-sulfonic acid (2,2,2-trifluoro-1-methyl-ethyl)-amide as a yellow solid (0.40 g, 84%); Melting point: 239-240° C.; MS m/z 493.2 M+H+; 1H NMR (500 MHz, CD3COCD3) δ 9.24 (dd, J=2.30, 0.65 Hz, 1H), 8.50 (dd, J=8.25, 2.35 Hz, 1H), 8.42 (s, 1H), 8.10 (dd, J=8.25, 0.85 Hz, 1H), 7.47 (bs, 1H), 7.54 (s, 1H), 7.15 (s, 1H), 5.30-5.26 (m, 1H), 4.40-4.35 (m, 1H), 2.40 (s, 3H), 2.34-2.31 (m, 2H), 2.16-2.14 (m, 2H), 2.10-2.07 (m, 2H), 1.74-1.72 (m, 2H), 1.21 (d, J=2.25 Hz, 3H).

Workup

  1. temperatureThe mixture was then cooled to room temperature
  2. filtrationfiltered through a silica-celite pad
  3. concentrationThe filtrate was concentrated
  4. dissolutiondissolved in acetone (10 mL)
  5. temperaturecooled to 0° C
  6. additionInto this solution was added an aqueous solution of Oxone (10 mL, 1.0 M)
  7. stirringThe mixture was stirred at room temperature for 15 min
  8. additiondiluted with ethyl acetate and water
  9. extractionThe aqueous layer was extracted with ethyl acetate
  10. extractionThe organic extractions
  11. washwashed with aq. NaHSO3 and brine
  12. dry with materialdried over Na2SO4
  13. concentrationconcentrated
  14. customPurification on silica gel eluting with 40% ethyl acetate in hexane

Sources & evidence

ORD record
ord-4221ac10fde245e0a75b832d25f4e39c
Source dataset
uspto-grants-2014_05
Patent number
US08735414B2

Reaction notes

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