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

反応式

HRID 81265 の反応式
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

参加物

5

反応物 3

HCID 10796Cesium carbonateHCID 201118775-Chloropyridine-3-boronic acidHCID 86724611HCID 86724611、化合物

生成物 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

試薬・触媒・溶媒 1

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

反応条件

温度
90 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-7d4282254eeb43d18ef7d6baf6d9dc3b
出典データセット
uspto-grants-2014_09
特許番号
US08846657B2

関連ノート

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