Pivaloyl chloride → N-{2-tert-Butyl-1-[(4,4-difluorocyclohexyl)methyl]-1H-benzimidazol-5-yl}acetamide

HRID 230713Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 230713
[NH2:1][C:2]1[CH:3]=[C:4]([NH:18][C:19](=[O:21])[CH3:20])[CH:5]=[CH:6][C:7]=1[NH:8][CH2:9][CH:10]1[CH2:15][CH2:14][C:13]([F:17])([F:16])[CH2:12][CH2:11]1.[CH3:22][C:23]([CH3:28])([CH3:27])[C:24](Cl)=O>C(Cl)Cl.CN(C1C=CN=CC=1)C>[C:23]([C:28]1[N:8]([CH2:9][CH:10]2[CH2:15][CH2:14][C:13]([F:17])([F:16])[CH2:12][CH2:11]2)[C:7]2[CH:6]=[CH:5][C:4]([NH:18][C:19](=[O:21])[CH3:20])=[CH:3][C:2]=2[N:1]=1)([CH3:27])([CH3:24])[CH3:22]

Komponenten

5

Edukt 2

HCID 62493Pivaloyl chlorideHCID 57441085N-(3-Amino-4-{[(4,4-difluorocyclohexyl)methyl]amino}phenyl)acetamide

Produkt 1

HCID 57723211N-{2-tert-Butyl-1-[(4,4-difluorocyclohexyl)methyl]-1H-benzimidazol-5-yl}acetamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

N-(3-Amino-4-{[(4,4-difluorocyclohexyl)methyl]amino}phenyl)acetamide (1.32 g, 4.44 mmol) was dissolved in 100 mL of DCM containing DMAP (108 mg, 0.89 mmol). Trimethylacetyl chloride (0.60 mL, 4.88 mmol) was added dropwise and the solution was stirred at rt for 2 h. The solution washed with saturated aqueous NaHCO3 solution, saturated aqueous NaCl solution and dried over anhydrous Na2SO4. Part of the product precipitated during the washings and was filtered. The organic phase was evaporated and combined with the precipitate. The product was dissolved in 30 mL of AcOH and placed in 6 sealed tubes (5 mL/tube). Each tube was heated at 150° C. in a Personal Chemistry microwaves instrument for 2.5 h. The fractions were pooled and the solvent was evaporated. The product was dissolved in EtOAc and washed with aqueous NaHCO3 solution, saturated aqueous NaCl solution and dried over anhydrous Na2SO4. The product was purified by silica gel flash chromatography using 2:1/acetone:hexanes as eluent. Yield: 1.11 g (68%). 1H NMR (400 MHz, METHANOL-D4) δ 1.40-1.49 (m, 2H), 1.52 (s, 9H), 1.60-1.65 (m, 2H), 1.67-1.77 (m, 1H), 1.96-2.06 (m, 3H), 2.11 (s, 3H), 2.15-2.23 (m, 1H), 4.28 (d, J=7.62 Hz, 2H), 7.35-7.39 (m, 1H), 7.40-7.44 (m, 1H), 7.85 (d, J=1.76 Hz, 1H).

Aufarbeitung

  1. washThe solution washed with saturated aqueous NaHCO3 solution, saturated aqueous NaCl solution
  2. dry with materialdried over anhydrous Na2SO4
  3. customPart of the product precipitated during the washings
  4. filtrationwas filtered
  5. customThe organic phase was evaporated
  6. dissolutionThe product was dissolved in 30 mL of AcOH
  7. temperatureEach tube was heated at 150° C. in a Personal Chemistry microwaves instrument for 2.5 h
  8. customthe solvent was evaporated
  9. dissolutionThe product was dissolved in EtOAc
  10. washwashed with aqueous NaHCO3 solution, saturated aqueous NaCl solution
  11. dry with materialdried over anhydrous Na2SO4
  12. customThe product was purified by silica gel flash chromatography

Quellen und Nachweise

ORD-Eintrag
ord-40c9b309d42e4d35b593d5ed816f3ce7
Quelldatensatz
uspto-grants-2009_07
Patentnummer
US07566788B2

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