Cesium carbonate → 6-chloro-4-(5-chloropyridin-3-yl)-2-[(trans)-hexahydrocyclopenta[b][1,4]oxazin-4(4aH)-yl]-3-[4-(trifluoromethyl)benzyl]-3H-imidazo[4,5-c]pyridine

HRID 81265

Reaction equation

HRID 81265 reaction equation
Cl[C:2]1[C:7]2[N:8]([CH2:20][C:21]3[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][CH:22]=3)[C:9]([N:11]3[CH2:16][CH2:15][O:14][C@@H:13]4[CH2:17][CH2:18][CH2:19][C@@H:12]34)=[N:10][C:6]=2[CH:5]=[C:4]([Cl:31])[N:3]=1.[Cl:32][C:33]1[CH:34]=[C:35](B(O)O)[CH:36]=[N:37][CH:38]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[Cl:31][C:4]1[N:3]=[C:2]([C:35]2[CH:36]=[N:37][CH:38]=[C:33]([Cl:32])[CH:34]=2)[C:7]2[N:8]([CH2:20][C:21]3[CH:22]=[CH:23][C:24]([C:27]([F:29])([F:28])[F:30])=[CH:25][CH:26]=3)[C:9]([N:11]3[CH2:16][CH2:15][O:14][C@@H:13]4[CH2:17][CH2:18][CH2:19][C@@H:12]34)=[N:10][C:6]=2[CH:5]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 201118775-Chloropyridine-3-boronic acidHCID 86724611HCID 86724611, compound

Product 1

HCID 867246126-chloro-4-(5-chloropyridin-3-yl)-2-[(trans)-hexahydrocyclopenta[b][1,4]oxazin-4(4aH)-yl]-3-[4-(trifluoromethyl)benzyl]-3H-imidazo[4,5-c]pyridine

Reagents, catalysts & solvents 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Conditions

Temperature
90 °C

Procedure

4,6-dichloro-2-[(trans)-hexahydrocyclopenta[b][1,4]oxazin-4(4aH)-yl]-3-[4-(trifluoromethyl)benzyl]-3H-imidazo[4,5-c]pyridine (racemate, 180 mg, 0.38 mmol), 5-chloropyridine-3-boronic acid (65.7 mg, 0.42 mmol), cesium carbonate (617 mg, 1.9 mmol), and 1,1′-Bis(diphenylphosphino) ferrocene-palladium(II)dichloride (46.3 mg, 0.076 mmol) were combined in a vial that had been oven-dried and flushed with nitrogen. Dioxane (75 mL) was added, and the vial was sealed and heated to 90° C. for 4 hours. The reaction mixture was cooled to room temperature, filtered through celite, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography (0-100% ethyl acetate/hexanes, linear gradient) to afford 6-chloro-4-(5-chloropyridin-3-yl)-2-[(trans)-hexahydrocyclopenta[b][1,4]oxazin-4(4aH)-yl]-3-[4-(trifluoromethyl)benzyl]-3H-imidazo[4,5-c]pyridine (racemic). MS APCl calc'd. for C26H22Cl2F3N5O [M+H]+ 548. found 548.

Workup

  1. customhad been oven-dried
  2. customflushed with nitrogen
  3. additionDioxane (75 mL) was added
  4. customthe vial was sealed
  5. temperatureThe reaction mixture was cooled to room temperature
  6. filtrationfiltered through celite
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customThe residue was purified by silica gel chromatography (0-100% ethyl acetate/hexanes, linear gradient)

Sources & evidence

ORD record
ord-7d4282254eeb43d18ef7d6baf6d9dc3b
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Linked notes

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