Sulfuric Acid → HCID 178455733、化合物

HRID 1852817ノート

反応式

HRID 1852817 の反応式
C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.S(=O)(=O)(O)O.Cl[C:53]1[N:58]=[C:57]([C:59]2[CH:60]=[N:61][CH:62]=[C:63]([Cl:65])[CH:64]=2)[C:56]2[N:66]([CH:69]([C@H:71]3[CH2:76][CH2:75][C@H:74]([CH3:77])[CH2:73][CH2:72]3)[CH3:70])[CH:67]=[N:68][C:55]=2[CH:54]=1.[CH3:78][N:79](C)C(=O)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.[C-]#N.[Zn+2].[C-]#N.[Zn]>[Cl:65][C:63]1[CH:64]=[C:59]([C:57]2[C:56]3[N:66]([CH:69]([C@H:71]4[CH2:76][CH2:75][C@H:74]([CH3:77])[CH2:73][CH2:72]4)[CH3:70])[CH:67]=[N:68][C:55]=3[CH:54]=[C:53]([C:78]#[N:79])[N:58]=2)[CH:60]=[N:61][CH:62]=1

参加物

8

反応物 4

HCID 1118Sulfuric AcidHCID 31374DimethylacetamideHCID 634876Binap, (A+-)-HCID 178455731HCID 178455731、化合物

生成物 1

HCID 178455733HCID 178455733、化合物

試薬・触媒・溶媒 3

HCID 11186Zinc cyanide (Zn(CN)2)触媒HCID 23994Zinc触媒HCID 167845palladium(II) acetate触媒

反応条件

温度
80 °C

実験手順

In an oven-dried, nitrogen cooled flask were placed palladium(II) acetate (286 mg, 1.27 mmol) and (R)-(+)-2,2′-Bis(diphenylphosphino)-1,1′-binaphthyl (793 mg, 1.27 mmol). N,N-dimethylacetamide (76 mL) was added and degassed for three minutes with nitrogen (sparge). Sulfuric acid (0.068 mL, 1.27 mmol) was added and degassed for three minutes with nitrogen (sparge). The flask was sealed and heated to 80° C. for 30 minutes. The mixture was cooled to room temperature and added to a separate nitrogen purged flask containing racemic 6-chloro-4-(5-chloropyridin-3-yl)-3-[1-(trans-4-methylcyclohexyl)ethyl]-3H-imidazo[4,5-c]pyridine (4.96 g, 12.7 mmol), zinc cyanide (748 mg, 6.37 mmol), and zinc (83 mg, 1.27 mmol). The flask was purged with nitrogen for five minutes and sealed and heated to 80° C. for 16 hours. The reaction mixture was cooled to room temperature, filtered, diluted with ethyl acetate, and washed with water and brine. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (0-100% ethyl acetate/hexanes, linear gradient) to afford racemic 4-(5-chloropyridin-3-yl)-3-[1-(trans-4-methylcyclohexyl)ethyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile. MS ESI calc'd. for C21H22ClN5 [M+H]+ 380. found 380.

後処理

  1. customdegassed for three minutes with nitrogen (sparge)
  2. customdegassed for three minutes with nitrogen (sparge)
  3. customThe flask was sealed
  4. temperatureThe mixture was cooled to room temperature
  5. additionadded to a separate nitrogen purged flask
  6. customThe flask was purged with nitrogen for five minutes
  7. customsealed
  8. temperatureheated to 80° C. for 16 hours
  9. temperatureThe reaction mixture was cooled to room temperature
  10. filtrationfiltered
  11. additiondiluted with ethyl acetate
  12. washwashed with water and brine
  13. dry with materialThe organic layer was dried over sodium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated under reduced pressure
  16. 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-e4cf6a9937c843b6bb73e7baa1138da4
出典データセット
uspto-grants-2015_02
特許番号
US08962611B2

反応ノート

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