2-Amino-3-methylpyridine → 3-Cyano-N-((1S)-3-hydroxy-1-{[4-(8-methylimidazo[1,2-a]pyridin-2-yl)phenyl]methyl}propyl)-4-[(1-methylethyl)oxy]benzamide

HRID 1785034

Reaktionsgleichung

Reaktionsgleichung von HRID 1785034
Br[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([CH2:11][C@H:12]([NH:16][C:17](=[O:30])[C:18]2[CH:23]=[CH:22][C:21]([O:24][CH:25]([CH3:27])[CH3:26])=[C:20]([C:28]#[N:29])[CH:19]=2)[CH2:13][CH2:14][OH:15])=[CH:7][CH:6]=1)=O.[NH2:31][C:32]1[C:37]([CH3:38])=[CH:36][CH:35]=[CH:34][N:33]=1.C([O-])(O)=O.[Na+]>CC(O)C>[C:28]([C:20]1[CH:19]=[C:18]([CH:23]=[CH:22][C:21]=1[O:24][CH:25]([CH3:27])[CH3:26])[C:17]([NH:16][C@@H:12]([CH2:11][C:8]1[CH:7]=[CH:6][C:5]([C:3]2[N:31]=[C:32]3[C:37]([CH3:38])=[CH:36][CH:35]=[CH:34][N:33]3[CH:2]=2)=[CH:10][CH:9]=1)[CH2:13][CH2:14][OH:15])=[O:30])#[N:29]

Komponenten

5

Edukt 3

HCID 153472-Amino-3-methylpyridineHCID 516892Sodium BicarbonateHCID 86604762N-((1S)-1-{[4-(bromoacetyl)phenyl]methyl}-3-hydroxypropyl)-3-cyano-4-[(1-methylethyl)oxy]benzamide

Produkt 1

HCID 116199833-Cyano-N-((1S)-3-hydroxy-1-{[4-(8-methylimidazo[1,2-a]pyridin-2-yl)phenyl]methyl}propyl)-4-[(1-methylethyl)oxy]benzamideAusbeute 70,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 3776IsopropanolLösungsmittel

Versuchsvorschrift

To a solution of N-((1S)-1-{[4-(bromoacetyl)phenyl]methyl}-3-hydroxypropyl)-3-cyano-4-[(1-methylethyl)oxy]benzamide (300 mg, 0.634 mmol) in i-PrOH (6 mL) was added 2-amino-3-picoline (Aldrich, 69 mg, 0.634 mmol) followed by solid NaHCO3 (64 mg, 0.761 mmol). The resultant suspension was heated to 80° C. After 7 h, a majority of the i-PrOH was removed under reduced pressure and the residue was dissolved in 3% MeOH/EtOAc (30 mL) and washed with water (10 mL) and brine (10 mL). The combined aqueous layers were extracted with 3% MeOH/EtOAc (30 mL) and the combined extracts were dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified by reverse phase HPLC (MeCN/H2O with 0.1% TFA) and the clean fractions were adjusted to pH ˜8 with saturated aqueous NaHCO3 and extracted with 3% MeOH/EtOAc (3×30 mL). The extracts were dried (Na2SO4), filtered and concentrated under reduced pressure to give 215 mg (70%) of the title compound as a pale yellow solid. LC/MS (ES) m/e 483.2 (M+H)+.

Aufarbeitung

  1. customa majority of the i-PrOH was removed under reduced pressure
  2. dissolutionthe residue was dissolved in 3% MeOH/EtOAc (30 mL)
  3. washwashed with water (10 mL) and brine (10 mL)
  4. extractionThe combined aqueous layers were extracted with 3% MeOH/EtOAc (30 mL)
  5. dry with materialthe combined extracts were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by reverse phase HPLC (MeCN/H2O with 0.1% TFA)
  9. extractionextracted with 3% MeOH/EtOAc (3×30 mL)
  10. dry with materialThe extracts were dried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-5b4a8f3b0f7347b4a1f638591e81ba41
Quelldatensatz
uspto-grants-2009_03
Patentnummer
US07504413B2

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